Lorrin Koran

All Publications

• Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI. Toxics Denmark, D., Ruhoy, I., Wittmann, B., Ashki, H., Koran, L. M. 2022; 10 (2)

  Abstract

  Despite the impressive safety of gadolinium (Gd)-based contrast agents (GBCAs), a small number of patients report the onset of new, severe, ongoing symptoms after even a single exposure-a syndrome termed Gadolinium Deposition Disease (GDD). Mitochondrial dysfunction and oxidative stress have been repeatedly implicated by animal and in vitro studies as mechanisms of Gd/GBCA-related toxicity, and as pathogenic in other diseases with similarities in presentation. Here, we aimed to molecularly characterize and explore potential metabolic associations with GDD symptoms. Detailed clinical phenotypes were systematically obtained for a small cohort of individuals (n = 15) with persistent symptoms attributed to a GBCA-enhanced MRI and consistent with provisional diagnostic criteria for GDD. Global untargeted mass spectroscopy-based metabolomics analyses were performed on plasma samples and examined for relevance with both single marker and pathways approaches. In addition to GDD criteria, frequently reported symptoms resembled those of patients with known mitochondrial-related diseases. Plasma differences compared to a healthy, asymptomatic reference cohort were suggested for 45 of 813 biochemicals. A notable proportion of these are associated with mitochondrial function and related disorders, including nucleotide and energy superpathways, which were over-represented. Although early evidence, coincident clinical and biochemical indications of potential mitochondrial involvement in GDD are remarkable in light of preclinical models showing adverse Gd/GBCA effects on multiple aspects of mitochondrial function. Further research on the potential contributory role of these markers and pathways in persistent symptoms attributed to GBCA exposure is recommended.

  View details for DOI 10.3390/toxics10020056

  View details for PubMedID 35202243

• Dynamic Serial Cytokine Measurements During Intravenous Ca-DTPA Chelation in Gadolinium Deposition Disease and Gadolinium Storage Condition: A Pilot Study. Investigative radiology Maecker, H. T., Siebert, J. C., Rosenberg-Hasson, Y., Koran, L. M., Ramalho, M., Semelka, R. C. 2021

  Abstract

  PURPOSE: The aim of this study was to investigate the feasibility of measuring early changes in serum cytokine levels after intravenous diethylenetriaminepentaacetic acid (Ca-DTPA) chelation in patients manifesting either gadolinium deposition disease (GDD) or gadolinium storage condition (GSC) and the possible usefulness of this method in further research.METHODS: Four patients with recent-onset GDD (≤1 year) and 2 patients with long-standing GSC (4 and 9 years) underwent chelation with intravenous bolus administration of Ca-DTPA. Multiple blood draws were performed to measure serum cytokines: at T = 0 (before Ca-DTPA injection) and 1, 5, 10, 30, 60 minutes, and 24 hours after Ca-DTPA injection. Patients rated the severity of GDD symptom flare at 24 hours. The 24-hour urine Gd amounts were measured prechelation and for the 24 hours after chelation. Serum samples were analyzed blind to whether patients had GDD or GSC but with knowledge of the time points characterizing each sample.RESULTS: Urine samples for both GDD and GSC patients showed increases in Gd postchelation. All GDD patients experienced flare reactions postchelation; the 2 GSC patients did not. Two cytokines, EGF and sCD40L, peaked at 30 minutes postchelation in at least 4 of the 6 participants. Three cytokines, ENA78/CXCL5, EOTAXIN/CCL11, and LEPTIN, peaked at 24 hours in at least 4 of the 6 participants. Two participants were high outliers for a large number of cytokines across time points. No clear distinction between GDD and GSC was apparent from the cytokine patterns, although differences were present.CONCLUSIONS: This pilot study describes precise temporal resolution (in the range of minutes) after a cytokine-inciting event. Select cytokines exhibited peak values at different time points. At this preliminary stage of investigation, peak cytokine release seems to reflect the amount of Gd mobilized rather than the severity of the patient symptomatic reaction. Too few subjects were studied to support statistical analysis between GDD and GSC groups, although differences were observed through visual data analysis.

  View details for DOI 10.1097/RLI.0000000000000803

  View details for PubMedID 34120127

• Specialty knowledge and competency standards for pharmacotherapy for adult obsessive-compulsive disorder. Psychiatry research Pittenger, C., Brennan, B. P., Koran, L., Mathews, C. A., Nestadt, G., Pato, M., Phillips, K. A., Rodriguez, C. I., Simpson, H. B., Skapinakis, P., Stein, D. J., Storch, E. A. 2021; 300: 113853

  Abstract

  Obsessive-compulsive disorder (OCD) affects approximately one person in 40 and causes substantial suffering. Evidence-based treatments can benefit many; however, optimal treatment can be difficult to access. Diagnosis is frequently delayed, and pharmacological and psychotherapeutic interventions often fail to follow evidence-based guidelines. To ameliorate this distressing situation, the International OCD Accreditation Task Force of the Canadian Institute for Obsessive-Compulsive Disorders has developed knowledge and competency standards for specialized treatments for OCD through the lifespan. These are foundational to evidence-based practice and will form the basis for upcoming ATF development of certification/accreditation programs. Here, we present specialty standards for the pharmacological treatment of adult OCD. We emphasize the importance of integrating pharmacotherapy with clear diagnosis, appreciation of complicating factors, and evidence-based cognitive behavioral therapy. Clear evidence exists to inform first- and second-line pharmacological treatments. In disease refractory to these initial efforts, multiple strategies have been investigated, but the evidence is more equivocal. These standards summarize this limited evidence to give the specialist practitioner a solid basis on which to make difficult decisions in complex cases. It is hoped that further research will lead to development of a clear, multi-step treatment algorithm to support each step in clinical decision-making.

  View details for DOI 10.1016/j.psychres.2021.113853

  View details for PubMedID 33975093

• Acute Chelation Therapy-Associated Changes in Urine Gadolinium, Self-reported Flare Severity, and Serum Cytokines in Gadolinium Deposition Disease. Investigative radiology Maecker, H. T., Siebert, J. C., Rosenberg-Hasson, Y. n., Koran, L. M., Ramalho, M. n., Semelka, R. C. 2021

  Abstract

  The aim of this study was to determine the following in patients who have undergone magnetic resonance imaging with gadolinium-based contrast agents (GBCAs) and meet the proposed diagnostic criteria for gadolinium deposition disease (GDD): (1) the effectiveness of chelation therapy (CT) with intravenous Ca-diethylenetriaminepentaacetic acid in removing retained gadolinium (Gd) and factors affecting the amount removed; (2) the frequency of CT-induced Flare, that is, GDD diagnostic symptom worsening, and factors affecting Flare intensity; (3) whether, as reported in a separate cohort, GDD patients' serum cytokine levels differ significantly from those in healthy normal controls and change significantly in response to CT; and (4) whether urine Gd, Flare reaction, and serum cytokine findings in GDD patients are mimicked in non-ill patients described as having gadolinium storage condition (GSC).Twenty-one GDD subjects and 3 GSC subjects underwent CT. Patients provided pre-CT and post-CT 24-hour urine samples for Gd content determination along with pre-CT and 24-hour post-CT serum samples for cytokine analysis. Patients rated potential Flare 24 hours after CT. Pre-CT and post-CT 24-hour urine Gd analyses and Luminex serum cytokine assays were performed blind to patients' GDD and GSC status and all other data except age and sex. Serum cytokine levels in a healthy normal control group of age- and sex-matched subjects drawn from Stanford influenza vaccination studies were measured once, contemporaneously with those of GDD and GSC patients, using the same Luminex assay.Urine Gd amounts increased post-CT by 4 times or more after 87% of the 30 CT sessions. The most important factors appeared to be the time since the last GBCA dose and the cumulative dose received. Urine Gd amounts for GDD and GSC patients fell in the same ranges. All GDD patients, and no GSC patient, reported a Flare 24 hours post-CT. Linear regression found that Flare intensity was significantly predicted by a model including pre- and post-CT Gd amounts and the number of GBCA-enhanced magnetic resonance imaging. Post-CT, multiple cytokines showed strong positive relationships with GDD patients' Flare intensity in multivariable models. The pre-CT serum levels of 12 cytokines were significantly different in GDD patients compared with healthy flu vaccine controls. The small number of GSC patients precluded analogous statistical testing. Post-CT, GDD patients' serum levels of 20 cytokines were significantly decreased, and 2 cytokines significantly increased. These cytokines did not exhibit the same change pattern in the 3 GSC patients. The small number of GSC patients precluded statistical comparisons of GSC to GDD patients' results.In this preliminary study, 24-hour urine Gd content increased markedly and similarly in GDD and GSC patients after Ca-diethylenetriaminepentaacetic acid CT. Post-CT Flare reaction developed only in GDD patients. The current study is the second finding significantly different serum cytokine levels in GDD patients compared with healthy normal controls. These differences and the difference between GDD and GSC patients' Flare and cytokine responses to CT suggest some inflammatory, immunologic, or other physiological differences in patients with GDD. Further research into the treatment and physiological underpinnings of GDD is warranted.

  View details for DOI 10.1097/RLI.0000000000000752

  View details for PubMedID 33449576

• Altered Functional Mitochondrial Protein Levels in Plasma Neuron-Derived Extracellular Vesicles of Patients With Gadolinium Deposition. Frontiers in toxicology Goetzl, E. J., Maecker, H. T., Rosenberg-Hasson, Y., Koran, L. M. 2021; 3: 797496

  Abstract

  The retention of the heavy metal, gadolinium, after a Gadolinium-Based Contrast Agent-assisted MRI may lead to a symptom cluster termed Gadolinium Deposition Disease. Little is known of the disorder's underlying pathophysiology, but a recent study reported abnormally elevated serum levels of pro-inflammatory cytokines compared to normal controls. As a calcium channel blocker in cellular plasma and mitochondrial membranes, gadolinium also interferes with mitochondrial function. We applied to sera from nine Gadolinium Deposition Disease and two Gadolinium Storage Condition patients newly developed methods allowing isolation of plasma neuron-derived extracellular vesicles that contain reproducibly quantifiable levels of mitochondrial proteins of all major classes. Patients' levels of five mitochondrial functional proteins were statistically significantly lower and of two significantly higher than the levels in normal controls. The patterns of differences between study patients and controls for mitochondrial dynamics and mitochondrial proteins encompassing neuronal energy generation, metabolic regulation, ion fluxes, and survival differed from those seen for patients with first episode psychosis and those with Major Depressive Disorder compared to their controls. These findings suggest that mitochondrial dysfunction due to retained gadolinium may play a role in causing Gadolinium Deposition Disease. Larger samples of both GDD and GSC patients are needed to allow not only testing the repeatability of our findings, but also investigation of relationships of specific mitochondrial protein deficiencies or excesses and concurrent cytokine, genetic, or other factors to GDD's neurological and cognitive symptoms. Studies of neuronal mitochondrial proteins as diagnostic markers or indicators of treatment effectiveness are also warranted.

  View details for DOI 10.3389/ftox.2021.797496

  View details for PubMedID 35295151

• Accelerated Neuromodulation Therapy for Obsessive-Compulsive Disorder. Brain stimulation Williams, N. R., Sudheimer, K. D., Cole, E. J., Varias, A. D., Goldstein-Piekarski, A. N., Stetz, P. n., Lombardi, A. n., Filippou-Frye, M. n., van Roessel, P. n., Anderson, K. n., McCarthy, E. A., Wright, B. n., Sandhu, T. n., Menon, S. n., Jo, B. n., Koran, L. n., Williams, L. M., Rodriguez, C. I. 2021

  Abstract

  The open-label trial of Williams, Sudheimer, Cole, et al., suggests safety, feasibility, and high efficacy for treatment-refractory OCD of an accelerated, fMRI-guided, high-dose, cTBSmod protocol targeting the right frontal pole. Larger, randomized, controlled trials are needed to test the promising results of this pilot study. CLINICALTRIALS.GOV REGISTRY NUMBERS: NCT03404609.

  View details for DOI 10.1016/j.brs.2021.02.013

  View details for PubMedID 33631349

• An initial investigation of serum cytokine levels in patients with gadolinium retention. Radiologia brasileira Maecker, H. T., Wang, W., Rosenberg-Hasson, Y., Semelka, R. C., Hickey, J., Koran, L. M. 2020; 53 (5): 306–13

  Abstract

  Objective: To determine whether individuals with proposed gadolinium deposition disease (GDD) have elevated serum levels of pro-inflammatory and pro-fibrotic cytokines, and whether specific cytokines are correlated with certain symptoms.Materials and Methods: Twenty-four participants recruited between May 2016 and June 2017 met GDD diagnostic criteria. The 64 control subjects provided serum samples before prophylactic flu vaccination. Serum cytokine levels were obtained with Luminex serum cytokine assay using eBiosciences/Affymetrix human 62-plex kits. Wilcoxon rank-sum tests were performed to assess the difference between the median fluorescence intensity values for the participants and the control group. Generalized linear models were built to evaluate the association between each cytokine of interest and selected participant symptoms.Results: Serum levels of 14 cytokines, including nine pro-inflammatory cytokines, were statistically significantly elevated compared to controls (p ≤ 0.05). Hypotheses regarding pro-fibrotic cytokines and cytokine links to specific symptoms' intensity were not confirmed.Conclusion: The statistically significantly elevated cytokines may be markers of susceptibility to GDD or agents of symptom induction. These findings suggest that individuals developing symptoms characteristic of GDD after a contrast-assisted magnetic resonance imaging should be studied to investigate whether gadolinium retention and elevated cytokines may be related to their symptoms.

  View details for DOI 10.1590/0100-3984.2019.0075

  View details for PubMedID 33071374

• Promising Treatments for Obsessive-Compulsive Disorder: A Call for Additional Research. Current medicinal chemistry Koran, L. M., Aboujaoude, E. 2017

  Abstract

  Many patients with OCD respond partially or not at all to standard medications and cognitive behavioral therapy approaches, making alternate treatments necessary. We review the preliminary evidence that exists in support of the use of stimulants, high-dose caffeine, opiates, memantine, ondansetron, ketamine, and transcranial magnetic stimulation in some patients with OCD. Although limited by small or modest sample sizes, open-label study designs, and brief follow-up periods, studies suggest that each of these strategies can help some patients who have inadequately responded to first-line treatments. The existing data and the unmet needs of OCD patients justify research attention to further test these treatments' safety and efficacy. Previously untested drugs also deserve attention, especially as recent research has suggested new possible contributors to OCD pathophysiology. Similarly, psychotherapeutic interventions beyond CBT should be investigated, and treatments with preliminary evidence in OCD, including Acceptance Commitment Therapy, Danger Ideation Reduction Therapy, and technology-enabled interventions like computerized CBT and Virtual Reality Exposure Therapy, should be carefully tested.

  View details for DOI 10.2174/0929867324666170526120916

  View details for PubMedID 28552055

• Excoriation (skin-picking) disorder in adults: a cross-cultural survey of Israeli Jewish and Arab samples. Comprehensive psychiatry Leibovici, V., Koran, L. M., Murad, S., Siam, I., Odlaug, B. L., Mandelkorn, U., Feldman-Weisz, V., Keuthen, N. J. 2015; 58: 102-107

  Abstract

  We sought to estimate the lifetime prevalence of Excoriation (Skin-Picking) Disorder (SPD) in the Israeli adult population as a whole and compare SPD prevalence in the Jewish and Arab communities. We also explored demographic, medical and psychological correlates of SPD diagnosis.Questionnaires and scales screening for SPD, and assessing the severity of perceived stress, depression, obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), alcohol use, illicit drug use, and medical disorders were completed in a sample of 2145 adults attending medical settings.The lifetime prevalence of SPD was 5.4% in the total sample; it did not differ between genders or within Jewish and Arab subsamples. Severity of depression (p<0.001), OCD (p<0.001) and perceived stress (p=<0.001) were greater in the SPD positive sample. Similarly, diagnoses of BDD (p=0.02) and generalized anxiety (p=0.03) were significantly more common in the SPD-positive respondents. Alcohol use and illicit substance use were significantly more common among SPD positive respondents in the total sample (both p's=0.01) and the Jewish subsample (p=0.03 and p=0.02, respectively). Hypothyroidism was more prevalent in the SPD-positive Jewish subsample (p=0.02). In the total sample, diabetes mellitus was more common in women than in men (p=0.04).Lifetime SPD appears to be relatively common in Israeli adults and associated with other mental disorders. Differences in the self-reported medical and psychiatric comorbidities between the Jewish and Arab subsamples suggest the possibility of cross-cultural variation in the correlates of this disorder.

  View details for DOI 10.1016/j.comppsych.2014.12.008

  View details for PubMedID 25682319

• Treating Compulsive Buying Disorder Current Treatment Optons in Psychiatry; Eating and Other Impulse Control Disorders Section Koran, L. M., Aboujaoude, E. 2014; 1 (4): 315-324
• A double-blind, placebo-controlled trial of topiramate for pathological gambling WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY Berlin, H. A., Braun, A., Simeon, D., Koran, L. M., Potenza, M. N., McElroy, S. L., Fong, T., Pallanti, S., Hollander, E. 2013; 14 (2): 121-128

  Abstract

  Pathological gambling (PG) is an impulse control disorder characterized by recurrent gambling thoughts and behaviours that impair social functioning. Earlier studies suggested that topiramate may be effective in treating some impulse control disorders. We conducted the first randomized, controlled trial of topiramate in PG.PG patients were randomized to topiramate (N = 20) or placebo (N = 22) in this 14-week, double-blind, placebo-controlled, parallel-group trial. The primary outcome measure was change in the obsessions subscale of the Yale-Brown Obsessive-Compulsive Scale Modified for Pathological Gambling.Mixed regression models (time [weeks] × treatment) revealed no significant treatment effect of topiramate on the primary or secondary outcome measures. The most statistically robust findings involved reducing the Barratt Impulsiveness Scale (BIS) total score and Motor and Non-Planning subscale scores, for which topiramate outperformed placebo at merely a trend level (P < 0.1).The observed trend in BIS score reductions may warrant further investigation to study whether topiramate reduces clinically important impulsivity in PG. Treatment studies with larger samples and less stringent exclusion criteria are needed to produce results that can be generalized to pathological gamblers in the community.

  View details for DOI 10.3109/15622975.2011.560964

  View details for Web of Science ID 000315898700006

  View details for PubMedID 21486110

• Guideline Watch (March 2013): Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder, Psychiatryonline.org Psychiatryonline.org Koran, L. M., Simpson, H. B. 2013
• Obsessive-compulsive symptoms in schizophrenia: implications for future psychiatric classifications COMPREHENSIVE PSYCHIATRY Poyurovsky, M., Zohar, J., Glick, I., Koran, L. M., Weizman, R., Tandon, R., Weizman, A. 2012; 53 (5): 480-483

  Abstract

  Although obsessive-compulsive symptoms are not considered primary features, they are prevalent, independent of psychosis, and substantially modify clinical characteristics, course, treatment and prognosis of schizophrenia. The authors highlight the clinical significance of obsessive-compulsive symptoms in schizophrenia, provide diagnostic criteria for "schizo-obsessive" patients and address future directions for research.

  View details for DOI 10.1016/j.comppsych.2011.08.009

  View details for Web of Science ID 000305769000010

  View details for PubMedID 22036006

• A Double-Blind, Randomized, Controlled Trial of Fluoxetine Plus Quetiapine or Clomipramine Versus Fluoxetine Plus Placebo for Obsessive-Compulsive Disorder JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Diniz, J. B., Shavitt, R. G., Fossaluza, V., Koran, L., de Braganca Pereira, C. A., Miguel, E. C. 2011; 31 (6): 763-768

  Abstract

  Obsessive-compulsive disorder patients who do not improve sufficiently after treatment with a selective serotonin reuptake inhibitor might improve further if other drugs were added to the treatment regimen. The authors present a double-blind, placebo-controlled trial comparing the efficacy of adding quetiapine or clomipramine to a treatment regimen consisting of fluoxetine. Between May 2007 and March 2010, a total of 54 patients with a primary diagnosis of obsessive-compulsive disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and a current Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of at least 16, the score having dropped by less than 35% after fluoxetine monotherapy, were allocated to 1 of 3 arms (n = 18 per arm): quetiapine + fluoxetine (≤200 and ≤40 mg/d, respectively), clomipramine + fluoxetine (≤75 and ≤40 mg/d, respectively), or placebo + fluoxetine (≤80 mg/d of fluoxetine). Follow-up was 12 weeks. The Y-BOCS scores were the main outcome measure. No severe adverse events occurred during the trial, and 40 patients (74%) completed the 12-week protocol. The Y-BOCS scores (mean [SD]) were significantly better in the placebo + fluoxetine and clomipramine + fluoxetine groups than in the quetiapine + fluoxetine group (final: 18 [7] and 18 [7], respectively, vs 25 [6], P < 0.001) (reduction from baseline: -6.7 [confidence interval {CI}, -9.6 to -3.8; and -6.5 [CI, -9.0 to -3.9], respectively, vs -0.1 [CI, -2.9 to 2.7], P < 0.001; number needed to treat = 2.4). The clomipramine-fluoxetine combination is a safe and effective treatment for fluoxetine nonresponders, especially those who cannot tolerate high doses of fluoxetine. However, the period of monotherapy with the maximum dose of fluoxetine should be extended before a combination treatment strategy is applied.

  View details for DOI 10.1097/JCP.0b013e3182367aee

  View details for Web of Science ID 000296742000014

  View details for PubMedID 22020357

• Patients with obsessive-compulsive disorder vs depression have comparable health care costs: A retrospective claims analysis of Florida Medicaid enrollees ANNALS OF CLINICAL PSYCHIATRY Hankin, C. S., Koran, L., Sheehan, D. V., Hollander, E., Culpepper, L., Black, D. W., Knispel, J., Dunn, J., Dougherty, D. D., Bronstone, A., Wang, Z. 2011; 23 (4): 285-296

  Abstract

  The health care burden of obsessive-compulsive disorder (OCD) is relatively unknown.To compare the health care burden of patients with OCD vs depression.This retrospective claims analysis compared the 2-year median per-patient health care claims and costs for Florida Medicaid adult enrollees (1997 to 2006) newly diagnosed with "pure OCD" (P-OCD; OCD without comorbid major depression, bipolar disorder, psychosis, organic mental disorder, pervasive developmental disorder, nonpsychotic brain damage, developmental delay, or mental retardation) with matched patients newly diagnosed with "pure depression" (P-D; similar to P-OCD but excluding OCD instead of depression).Eighty-five newly diagnosed P-OCD patients were matched with 14,906 P-D patients. Although median per-patient total health care costs were comparable across groups, patients with P-D incurred significantly higher median outpatient medical costs ($1,928 vs $363, P = .003), while those with P-OCD incurred almost three-fold greater psychiatric costs ($2,028 vs $759, P < .0001). The latter was due primarily to significantly higher costs of psychotropic medications among those with P-OCD ($4,307 vs $2,317, P = .0006) rather than to psychiatric outpatient care.Patients with P-D and P-OCD carry a similar burden in overall health care costs. However, the burden of those with P-D was largely attributable to outpatient medical costs while that of those with P-OCD was due to higher costs of psychotropic medications.

  View details for Web of Science ID 000297034500008

  View details for PubMedID 22073386

• Open-Label Trial of Aripiprazole in the Treatment of Trichotillomania JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY White, M. P., Koran, L. M. 2011; 31 (4): 503-506

  Abstract

  Serotonin reuptake inhibitors have been disappointing in the treatment of trichotillomania (TTM). Recent evidence suggests that medications that modulate dopamine may be helpful in this disorder.To determine if the D2 partial agonist aripiprazole would be effective in the treatment of TTM.Twelve subjects participated in an 8-week, open-label, flexible-dose study of aripiprazole treatment of TTM. Primary end points were reduction in the Massachusetts General Hospital Hair Pulling Scale (MGHHPS) and MGHHPS Actual Pulling Subscale (MGHHPS-APS). Secondary end points were the Clinical Global Impressions-Improvement Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Beck Depression Inventory, and Beck Anxiety Inventory.Eleven of 12 subjects had 2 or more assessments; one subject dropped out during the first week. For subjects with 2 or more assessments, there was a significant mean reduction in both primary end points, the MGHHPS score (mean change, 7.8; SD, ± 7.8; P ≤ 0.01) and the MGHHPS-APS score (mean change, 3.9; SD, ± 4.1; P ≤ 0.02). Seven subjects had a greater than 50% reduction in MGHHPS; 7 subjects had an exit Clinical Global Impressions-Improvement Scale of 2 or lower, and 5 participants had absolute exit scores of 3 or lower on the MGHHPS and 1 or lower on the MGHHPS-APS. There were no significant changes in mood-related secondary end points. The mean aripiprazole dose for all completers (N = 11) was 7.5 mg/d (± 3.4 mg/d).This small open-label study suggests that aripiprazole is a promising treatment for the treatment of trichotillomania. Larger double-blind, placebo-controlled studies are needed to follow up on these findings.

  View details for DOI 10.1097/JCP.0b013e318221b1ba

  View details for Web of Science ID 000292284600015

  View details for PubMedID 21694623

• Double-Blind, Placebo-Controlled Trial of Topiramate Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder JOURNAL OF CLINICAL PSYCHIATRY Berlin, H. A., Koran, L. M., Jenike, M. A., Shapira, N. A., Chaplin, W., Pallanti, S., Hollander, E. 2011; 72 (5): 716-721

  Abstract

  From 40% to 60% of obsessive-compulsive disorder (OCD) patients fail to tolerate or respond to selective serotonin reuptake inhibitors (SSRIs). Preclinical and neuroimaging studies have shown abnormally high glutamatergic concentrations in OCD patients and an association between decreased caudate glutamatergic concentrations and reduced OCD symptom severity after SSRI treatment. Topiramate inhibits glutamatergic conduction.Thirty-six adult patients with DSM-IV-defined OCD were randomly assigned to topiramate (n = 18) and placebo (n = 18) groups in this 12-week, double-blind, placebo-controlled, parallel-groups trial. Subjects were taking the maximum SSRI dose they could tolerate for at least 12 weeks and their current dose for at least 6 weeks, which was maintained throughout the study. Primary outcome measures were changes in the Yale-Brown Obsessive Compulsive Scale (YBOCS) total score and compulsions and obsessions subscores. Patients were recruited and followed up between April 1, 2003, and April 13, 2006.Using mixed regression models (time [weeks] × treatment), we found a significant treatment effect on the YBOCS compulsions (P = .014) subscale, but not the obsessions (P = .99) subscale or the total score (P = .11). Over the 12-week trial, the topiramate group (mean endpoint dose = 177.8 ± 134.2 mg/d; range, 50-400 mg/d) showed an average linear decrease of 5.38 points on the compulsions subscale compared to 0.6 points in the placebo group. Thirteen topiramate and 14 placebo subjects completed the study. Topiramate was not well tolerated in this trial: 28% (5/18) of the subjects discontinued the drug for adverse effects, and 39% (7/18) had a dose reduction for this reason.The results of this first double-blind, placebo-controlled trial of topiramate augmentation for treatment-resistant OCD suggest that topiramate may be beneficial for compulsions, but not obsessions. Modifications in glutamatergic function may be responsible, at least in part, for the improved response in compulsions seen with topiramate.clinicaltrials.gov Identifier: NCT00211744.

  View details for DOI 10.4088/JCP.09m05266gre

  View details for Web of Science ID 000291240600019

  View details for PubMedID 20816027

• Agitation in the Inpatient Psychiatric Setting: A Review of Clinical Presentation, Burden, and Treatment JOURNAL OF PSYCHIATRIC PRACTICE Hankin, C. S., Bronstone, A., Koran, L. M. 2011; 17 (3): 170-185

  Abstract

  Agitation among psychiatric inpatients (particularly those diagnosed with schizophrenia or bipolar disorder) is common and, unless recognized early and managed effectively, can rapidly escalate to potentially dangerous behaviors, including physical violence. Inpatient aggression and violence have substantial adverse psychological and physical consequences for both patients and providers, and they are costly to the healthcare system. In contrast to the commonly held view that inpatient violence occurs without warning or can be predicted by "static" risk factors, such as patient demographics or clinical characteristics, research indicates that violence is usually preceded by observable behaviors, especially non-violent agitation. When agitation is recognized, staff should employ nonpharmacological de-escalation strategies and, if the behavior continues, offer pharmacological treatment to calm patients rapidly. Given the poor therapeutic efficacy and potential for adverse events associated with physical restraint and seclusion, and the potential adverse sequelae of involuntary drug treatment, these interventions should be considered last resorts. Pharmacological agents used to treat agitation include benzodiazepines and first- and second-generation antipsychotic drugs. Although no currently available agent is ideal, recommendations for selecting among them are provided. There remains an unmet need for a non-invasive and rapidly acting agent that effectively calms without excessively sedating patients, addresses the patient's underlying psychiatric symptoms, and is reasonably safe and tolerable. A treatment with these characteristics could substantially reduce the clinical and economic burden of agitation in the inpatient psychiatric setting.

  View details for DOI 10.1097/01.pra.0000398410.21374.7d

  View details for Web of Science ID 000290724800003

  View details for PubMedID 21586995

• Psychiatric complications of treatment with corticosteroids: Review with case report PSYCHIATRY AND CLINICAL NEUROSCIENCES Kenna, H. A., Poon, A. W., de los Angeles, C. P., Koran, L. M. 2011; 65 (6): 549-560

  Abstract

  Corticosteroids are widely used in modern medicine but can result in troubling psychiatric side-effects. Physicians and other medical professionals should be aware of the potential for these side-effects, possible means of prevention, and efficacious treatments. Herein, we review adult case report data published during the past quarter-century on adverse corticosteroid-induced psychiatric effects, and present a case of corticosteroid-induced psychotic depression. PubMed and PsychLit databases were searched using the terms 'corticosteroids', 'steroids', and the generic names of corticosteroid medications with terms for psychiatric symptoms or syndromes, including psychosis, mania, hypomania, depression, apathy, anxiety, panic, depersonalization, delirium, confusion, hallucinations, delusions, paranoia, cognitive impairment and dementia. Fifty-five cases and a number of clinical trials investigating the incidence and treatment of these psychiatric symptoms and syndromes were identified. Data on incidence, drug dose, risk factors, course of illness and treatment (when present) were tabulated. We conclude that the cumulative data indicate that psychiatric complications of corticosteroid treatment are not rare and range from clinically significant anxiety and insomnia, to severe mood and psychotic disorders, delirium and dementia. While tapering or discontinuation of the corticosteroid treatment may remedy these adverse side-effects, psychotropic medications are often required because of the medical necessity of the corticosteroid or the severity of the psychiatric symptom. Further studies are needed to better understand the deleterious psychiatric effects associated with corticosteroids.

  View details for DOI 10.1111/j.1440-1819.2011.02260.x

  View details for Web of Science ID 000296045500002

  View details for PubMedID 22003987

• Extended-release fluvoxamine and improvements in quality of life in patients with obsessive-compulsive disorder COMPREHENSIVE PSYCHIATRY Koran, L. M., Bromberg, D., Hornfeldt, C. S., Shepski, J. C., Wang, S., Hollander, E. 2010; 51 (4): 373-379

  Abstract

  We hypothesized that subjects with obsessive-compulsive disorder (OCD) who received extended-release fluvoxamine (fluvoxamine ER) in a 12-week placebo-controlled trial would exhibit improvements in psychosocial domains of health-related quality of life (HRQOL) and that additional improvements would occur after a 40-week open-label extension trial. We also hypothesized that greater OCD symptom improvement in the first 12 weeks of treatment would be associated with greater HRQOL improvement after 52 weeks of treatment.In the 12-week placebo-controlled trial, subjects were randomized to receive placebo or 100 mg/d of fluvoxamine ER and then titrated in weekly 50 mg increments to a final dose of 100 to 300 mg/d. All subjects enrolled in the 40-week extension trial followed a similar titration, during which they were maintained on their highest well-tolerated dose.After 12 weeks of treatment, fluvoxamine ER subjects experienced significantly greater decreases than placebo subjects in Yale-Brown Obsessive-Compulsive Scale scores (P = .001). Both the active drug and placebo groups exhibited significant improvements in psychosocial domains of HRQOL; further improvement occurred after 40 weeks of open-label treatment with active drug. The greater the improvement in OCD severity at 12 weeks, the greater the improvement at 52 weeks in the psychosocial domains (Social Functioning r = -0.39, P = .027; Emotional Problems r = -0.37, P = .037; Mental Health r = -0.49, P = .004).Improvement in Yale-Brown Obsessive-Compulsive Scale severity scores during treatment with fluvoxamine ER was associated with improvements in psychosocial aspects of HRQOL that increased over an extended period of treatment.

  View details for DOI 10.1016/j.comppsych.2009.10.001

  View details for Web of Science ID 000279303500008

  View details for PubMedID 20579510

• Lamotrigine augmentation in schizophrenia and schizoaffective patients with obsessive-compulsive symptoms JOURNAL OF PSYCHOPHARMACOLOGY Poyurovsky, M., Glick, I., Koran, L. M. 2010; 24 (6): 861-866

  Abstract

  Obsessive-compulsive symptoms (OCS) are clinically important phenomena in schizophrenia patients. Lamotrigine has a modulating effect on glutamatergic neurotransmission relevant to pathophysiology of both schizophrenia and OCD. Efficacy and tolerability of lamotrigine in schizophrenia and schizoaffective patients with comorbid OCS were evaluated. In an 8-week, open-label trial, lamotrigine (25 mg/day for 1 week, 50 mg for 2 weeks, 100 mg for 2 weeks, 200 mg for 3 weeks) was added to ongoing psychotropic drug regimens in schizophrenia (N = 5) and schizoaffective disorder (N = 6) patients with clinically significant OCS [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score > 16]. The Y-BOCS score for nine completers decreased significantly from baseline to week 8 (22.9 +/- 6.1 vs 17.4 +/- 3.6; t = 2.33, df = 1, P = 0.033). Five patients, all with schizoaffective disorder, were responders (>or=35% decrease in Y-BOCS score). No significant changes were detected in schizophrenia symptom severity. Depressive symptoms, assessed with the Calgary Depression Rating Scale, improved significantly (6.4 +/- 1.5 vs 4.0 +/- 2.5; t = 3.19, df = 1, P = 0.013); this change positively correlated with OCS improvement (r = 0.69, P = 0.04). Lamotrigine was safe and well tolerated. Explicit evaluation of therapeutic efficacy of adjunctive lamotrigine in schizoaffective disorder patients with comorbid OCS merits further investigation.

  View details for DOI 10.1177/0269881108099215

  View details for Web of Science ID 000278089200008

  View details for PubMedID 19074541

• BODY DYSMORPHIC DISORDER: SOME KEY ISSUES FOR DSM-V DEPRESSION AND ANXIETY Phillips, K. A., Wilhelm, S., Koran, L. M., Didie, E. R., Fallon, B. A., Feusner, J., Stein, D. J. 2010; 27 (6): 573-591

  Abstract

  Body dysmorphic disorder (BDD), a distressing or impairing preoccupation with an imagined or slight defect in appearance, has been described for more than a century and increasingly studied over the past several decades. This article provides a focused review of issues pertaining to BDD that are relevant to DSM-V. The review presents a number of options and preliminary recommendations to be considered for DSM-V: (1) Criterion A may benefit from some rewording, without changing its focus or meaning; (2) There are both advantages and disadvantages to adding a new criterion to reflect compulsive BDD behaviors; this possible addition requires further consideration; (3) A clinical significance criterion seems necessary for BDD to differentiate it from normal appearance concerns; (4) BDD and eating disorders have some overlapping features and need to be differentiated; some minor changes to DSM-IV's criterion C are suggested; (5) BDD should not be broadened to include body integrity identity disorder (apotemnophilia) or olfactory reference syndrome; (6) There is no compelling evidence for including diagnostic features or subtypes that are specific to gender-related, age-related, or cultural manifestations of BDD; (7) Adding muscle dysmorphia as a specifier may have clinical utility; and (8) The ICD-10 criteria for hypochondriacal disorder are not suitable for BDD, and there is no empirical evidence that BDD and hypochondriasis are the same disorder. The issue of how BDD's delusional variant should be classified in DSM-V is briefly discussed and will be addressed more extensively in a separate article.

  View details for DOI 10.1002/da.20709

  View details for Web of Science ID 000278572700005

  View details for PubMedID 20533368

• The prevalence of pathologic skin picking in US adults COMPREHENSIVE PSYCHIATRY Keuthen, N. J., Koran, L. M., Aboujaoude, E., Large, M. D., Serpe, R. T. 2010; 51 (2): 183-186

  Abstract

  Despite increasing recognition of the potentially severe medical and psychosocial costs of pathologic skin picking (PSP), no large-sample, randomized investigation of its prevalence in a national population has been conducted.Two thousand five hundred and thirteen US adults were interviewed during the spring and summer of 2004 in a random-sample, national household computer-assisted phone survey of PSP phenomenology and associated functional impairment. Respondents were classified for subsequent analysis according to proposed diagnostic criteria.Of all respondents, 16.6% endorsed lifetime PSP with noticeable skin damage; 60.3% of these denied picking secondary to an inflammation or itch from a medical condition. One fifth to one quarter of those with lifetime PSP not related to a medical condition endorsed tension or nervousness before picking, tension or nervousness when attempting to resist picking, and pleasure or relief during or after picking. A total of 1.4% of our entire sample satisfied our criteria of picking with noticeable skin damage not attributable to another condition and with associated distress or psychosocial impairment. Pickers satisfying these latter criteria differed from other respondents in demographics (age, marital status) and both picking phenomenology and frequency.

  View details for DOI 10.1016/j.comppsych.2009.04.003

  View details for Web of Science ID 000285923000014

  View details for PubMedID 20152300

• Quetiapine versus clomipramine in the augmentation of selective serotonin reuptake inhibitors for the treatment of obsessive-compulsive disorder: a randomized, open-label trial JOURNAL OF PSYCHOPHARMACOLOGY Diniz, J. B., Shavitt, R. G., Pereira, C. A., Hounie, A. G., Pimentel, I., Koran, L. M., Dainesi, S. M., Miguel, E. C. 2010; 24 (3): 297-307

  Abstract

  After 12 weeks of selective serotonin reuptake inhibitor (SSRI) monotherapy with inadequate response, 10 patients received clomipramine and 11 received quetiapine as augmentation agents of the SSRI. The primary outcome measure was the difference between initial and final scores of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), rated in a blinded fashion, and the score of clinical global improvement (CGI-I). Statistical analyses were performed using nonparametric tests to evaluate treatment efficacy and the difference between treatment groups. Percentile plots were constructed with YBOCS scores from the clomipramine and quetiapine groups. Considering response a >or=35% reduction in the initial Y-BOCS score plus a rating of 'much improved' or 'very much improved' on CGI-I, four of eleven quetiapine patients and one out of ten clomipramine patients were classified as responders. The mean final Y-BOCS score was significantly lower than baseline in the quetiapine augmentation group (P = 0.023), but not in the clomipramine augmentation group (P = 0.503). The difference between groups showed a trend towards significance only at week 4, the mean Y-BOCS score being lower for those receiving quetiapine (P = 0.052). A difference between groups was also observed at week 4 according to percentile plots. These results corroborate previous findings of quetiapine augmentation efficacy in obsessive-compulsive disorder (OCD). Clomipramine augmentation did not produce a significant reduction in Y-BOCS scores. Higher target maximum dosages might have yielded different results.

  View details for DOI 10.1177/0269881108099423

  View details for Web of Science ID 000275230900002

  View details for PubMedID 19164490

• Impulse Control Disorders edited by Aboujaoude, E., Koran, L. M. Cambridge University Press. 2010
• Adequacy of Pharmacotherapy Among Medicaid-Enrolled Patients; Newly Diagnosed with Obsessive-Compulsive Disorder CNS SPECTRUMS Hankin, C. S., Koran, L. M., Bronstone, A., Black, D. W., Sheehan, D. V., Hollander, E., Dunn, J. D., Culpepper, L., Knispel, J., Dougherty, D. D., Wang, Z. 2009; 14 (12): 695-703

  Abstract

  To determine the adequacy of pharmacotherapy received by patients with newly-diagnosed obsessive-compulsive disorder (OCD), based on current practice guidelines.A 9 year (1997-2006) retrospective claims analysis of adults enrolled in Florida Medicaid for at least 3 continuous years was conducted to determine the percentage who received both a minimally effective duration (> 8 continuous weeks) and dose of first-line OCD pharmacotherapy during the year following their first ("index") OCD diagnosis.Among 2,960,421 adult (> 18 years of age) enrollees, 2,921 (0.1%) were diagnosed with OCD. Among the 2,825 OCD patients without comorbid Asperger syndrome or autism, 843 had newly-diagnosed OCD and at least 12 months of follow-up data after their index diagnosis. Among these 843 patients, 588 (69.7%) received first-line OCD pharmacotherapy but only 323 (38.3%) received a minimally effective pharmacotherapy trial in the year following their index diagnosis.Among clinically-diagnosed persons with OCD (<10% of those with the disorder), a minority of newly-diagnosed patients receive a minimally effective pharmacotherapy trial consistent with current standards of care. Reasons such as limited patient adherence and/or physician awareness of guidelines must be identified and redressed to ameliorate the patient, healthcare system, and economic burdens associated with OCD.

  View details for Web of Science ID 000273274100006

  View details for PubMedID 20394177

• The relationship between impulse-control disorders and obsessive-compulsive disorder: A current understanding and future research directions PSYCHIATRY RESEARCH Potenza, M. N., Koran, L. M., Pallanti, S. 2009; 170 (1): 22-31

  Abstract

  Impulse-control disorders (ICDs) constitute a heterogeneous group of conditions linked diagnostically by difficulties in resisting "the impulse, drive, or temptation to perform an act that is harmful to the person or to others." Specific ICDs share clinical, phenomenological and biological features with obsessive-compulsive disorder (OCD) that have suggested that these disorders might be categorized together. However, other data suggest significant differences between OCD and ICDs. In this article, clinical, phenomenological and biological features of the formal ICDs are reviewed and compared and contrasted with those of OCD. Available data indicate substantial differences between ICDs and OCD that suggest independent categorizations. Existing research gaps are identified and avenues for future research suggested.

  View details for DOI 10.1016/j.psychres.2008.06.036

  View details for Web of Science ID 000272023000005

  View details for PubMedID 19811840

  View details for PubMedCentralID PMC2792582

• Double-Blind Study of Dextroamphetamine Versus Caffeine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder 15th Annual Obsessive Compulsive Foundation Conference Koran, L. M., Aboujaoude, E., Gamel, N. N. PHYSICIANS POSTGRADUATE PRESS. 2009: 1530–35

  Abstract

  Two small, double-blind, placebo-controlled, single-dose, crossover studies found dextroamphetamine (d-amphetamine) 30 mg clearly superior to placebo in relieving symptoms of obsessive-compulsive disorder (OCD). We conducted a 5-week, double-blind, caffeine-controlled study to test the hypothesis that d-amphetamine, added after an adequate selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) trial, would be more effective than caffeine in reducing residual OCD symptoms of moderate or greater severity.Between August 2006 and February 2008, we enrolled adults with DSM-IV OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of >or= 20 after >or= 12 weeks of adequate treatment with an SSRI or SNRI. Subjects were randomly assigned to double-blind d-amphetamine 30 mg/d or caffeine 300 mg/d added to their SSRI/SNRI and other medications. Responders (first week mean Y-BOCS score decrease of >or= 20%) entered the study's 4-week double-blind extension phase.We enrolled 24 subjects, 11 women and 13 men, with a mean (SD) age of 40 (13.2) years and mean baseline Y-BOCS scores of 26.5 (4.1) for the d-amphetamine group (n = 12) and 29.1 (4.0) for the caffeine group (n = 12). At the end of week 1, 6 of 12 d-amphetamine subjects (50%) and 7 of 12 caffeine subjects (58%) were responders. At week 5, the responders' mean Y-BOCS score decreases were, for the d-amphetamine group (last observation carried forward), 48% (range, 20%-80%); and, for the caffeine group, 55% (range, 27%-89%). Obsessive-compulsive disorder and depression improvement were independent. The double-blind remained intact. No subject discontinued the study due to side effects.Larger, double-blind, placebo-controlled trials of both d-amphetamine and caffeine augmentation are needed in OCD subjects inadequately responsive to adequate doses of an SSRI or SNRI.clinicaltrials.gov Identifier: NCT00363298.

  View details for DOI 10.4088/JCP.08m04605

  View details for Web of Science ID 000272206200007

  View details for PubMedID 19573497

• Aripiprazole in Schizophrenia Patients With Comorbid Obsessive-Compulsive Symptoms: An Open-Label Study of 15 Patients JOURNAL OF CLINICAL PSYCHIATRY Glick, I. D., Poyurovsky, M., Ivanova, O., Koran, L. M. 2008; 69 (12): 1856-1859

  Abstract

  Approximately 15% of patients with schizophrenia also meet DSM-IV criteria for obsessive-compulsive disorder (OCD) at some point in their illness, a rate considerably higher than in the general population. This study examined aripiprazole treatment of patients with comorbid schizophrenia and obsessive-compulsive symptoms (OCS) that did not meet full criteria for OCD.Physically healthy adults aged 18 to 65 years with DSM-IV schizophrenia and a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (YBOCS) were eligible to participate in this 6-week, open-label, flexible-dose trial of aripiprazole monotherapy. Patients currently taking another antipsychotic medication were concurrently down-titrated from their current antipsychotic and up-titrated with aripiprazole, starting with 15 mg/day. Coadministration of the 2 medications lasted from 7 to 14 days, until a stable therapeutic dose of 10 to 30 mg/day was reached. Subjects were recruited into the study, which was conducted at the Schizophrenia Clinic of Stanford University School of Medicine, between January 2005 and December 2006.Of 15 eligible patients, 7 completed the trial. All 7 had at least minimal improvement on the YBOCS, the Clinical Global Impressions (CGI) scale, and the Positive and Negative Syndrome Scale (PANSS). At week 6, the mean CGI-Improvement scale score was 2.3 (much improved). Mean PANSS scores decreased from 75 to 56, a mean decrease of 21%, (p < .05). On the YBOCS, 6 of 7 completers showed a change of greater than 35% from baseline to week 6.These results suggest that aripiprazole monotherapy can modestly improve the outcome for some schizophrenia patients with obsessive-compulsive symptoms. Further studies with aripiprazole under controlled conditions are indicated for this population of patients. Overall, even modest improvement in global functioning due to an improvement in an OCS component may be clinically meaningful for this difficult-to-treat subset of schizophrenia patients.

  View details for Web of Science ID 000262059700002

  View details for PubMedID 19026264

• Obsessive-Compulsive Disorder: Strategies for Optimal Treatment JOURNAL OF CLINICAL PSYCHIATRY Hollander, E., Abramowitz, J. S., Koran, L. M., Pallanti, S. 2008; 69 (11): 1750-?

  View details for Web of Science ID 000261351800010

• Clinical characteristics of schizotypal-related obsessive-compulsive disorder PSYCHIATRY RESEARCH Poyurovsky, M., Faragian, S., Pashinian, A., Heidrach, L., Fuchs, C., Weizman, R., Koran, L. 2008; 159 (1-2): 254-258

  Abstract

  In this study we compared 15 patients with DSM-IV obsessive-compulsive disorder (OCD) and schizotypal personality disorder (SPD) and 31 non-SPD OCD patients. OCD-SPD patients had poorer insight, more negative symptoms, lower functioning, more antipsychotic augmentation and more first-degree relatives with schizophrenia-spectrum disorders. A distinct clinical phenotype of OCD associated with SPD should be considered when investigating etiopathogenetic mechanisms.

  View details for DOI 10.1016/j.psychres.2007.02.019

  View details for Web of Science ID 000256517700034

  View details for PubMedID 18378321

• The prevalence of body dysmorphic disorder in the United States adult population CNS SPECTRUMS Koran, L. M., Abuiaoude, E., Large, M. D., Serpe, R. T. 2008; 13 (4): 316-322

  Abstract

  In clinical samples, body dysmorphic disorder (BDD) is associated with substantial suffering and reduced quality of life. Limited surveys report widely varying prevalence estimates. To better establish the prevalence of BDD, we conducted a United States nationwide prevalence survey.We conducted a random sample national household telephone survey in the spring and summer of 2004 and interviewed 2,513 adults, of whom 2,048 qualified for the BDD-module administration. The computer-assisted, structured interviews, conducted by trained lay interviewers, addressed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BDD, along with information regarding several impulse-control disorders and the respondents' financial and demographic data.The rate of response was 56.3%, which compared favorably with rates in federal national health surveys. The cooperation rate was 97.6%. Respondents included a higher percentage of women and people >55 years of age than in the US adult population, and a lower percentage of Hispanics. The estimated point prevalence of DSM-IV BDD among respondents was 2.4% (49/2,048) (by gender: 2.5% for women, 2.2% for men), exceeding the prevalence of schizophrenia and bipolar disorder type I and about that of generalized anxiety disorder. BDD prevalence decreased after 44 years of age, and a larger proportion of BDD respondents were never married. Of those meeting DSM-IV criteria for BDD, 90% (45/49) met the DSM-IV distress criterion, and 51% (25/49) met the interference-with-functioning criterion.A study using clinically valid interviews is needed to evaluate these results. Such studies could inform treatment by documenting rates of seeking treatment from various sources, suicide attempt rates, and the prevalence of comorbid conditions.

  View details for Web of Science ID 000255381400013

  View details for PubMedID 18408651

• Duloxetine treatment of dysthymia and double depression: an open-label trial JOURNAL OF CLINICAL PSYCHIATRY Koran, L. M., Aboujaoude, E. N., Gamel, N. N. 2007; 68 (5): 761-765

  Abstract

  Although not as common as major depressive disorder, dysthymia is not rare and is associated with substantial impairment. Antidepressants and some psychotherapies are often effective. We explored the efficacy of the antidepressant duloxetine, a serotonin and norepinephrine reuptake inhibitor.Between February 2005 and April 2006, we recruited 24 adults with DSM-IV dysthymia or dysthymia and concurrent major depression ("double depression") who had an entry score of > or = 17 on the clinician-rated Inventory for Depressive Symptomatology (IDS-C). We excluded subjects with significant medical illnesses and those requiring other psychotropic agents or undergoing psychotherapy. Subjects received duloxetine 60 mg/day for 6 weeks, increased as tolerated to 120 mg/day for the remainder of the 12-week trial for those with an inadequate treatment response.The subjects' mean +/- SD IDS-C scores decreased significantly from baseline (27.3 +/- 6.3) to endpoint (7.8 +/- 7.4, Student t = 12.38, df = 23, p < or = .001). The IDS-C response rate (intent-to-treat [ITT]) was 83% (20/24); the remission rate (ITT) was 79% (19/24). Among study completers, these rates were 89% (17/19) and 84% (16/19). Five subjects (21%) discontinued for side effects.Duloxetine appears to be an effective and well-tolerated treatment for dysthymia and double depression. A double-blind, placebo-controlled study is under way. If duloxetine is found to be effective, studies powered to detect potential, clinically important differences between duloxetine and other antidepressants will be needed.ClinicalTrials.gov identifier NCT00185575.

  View details for PubMedID 17503986

• Escitalopram for compulsive buying disorder - A double-blind discontinuation study JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Koran, L. M., Aboujaoude, E. N., Solvason, B., Gamel, N. N., Smith, E. H. 2007; 27 (2): 225-227

  View details for Web of Science ID 000245094300027

  View details for PubMedID 17414257

• Escitalopram treatment of kleptomania: An open-label trial followed by double-blind discontinuation 18th Congress of the European-College-of-Neuropsychopharmacology Koran, L. M., Aboujaoude, E. N., Gamel, N. N. PHYSICIANS POSTGRADUATE PRESS. 2007: 422–27

  Abstract

  Kleptomania has no definitive treatment. Mixed reports of benefit from openly prescribed selective serotonin reuptake inhibitors led us to design a double-blind, placebo-controlled discontinuation trial of escitalopram.Between December 2002 and March 2005, we recruited 24 subjects aged >or=20 years with DSM-IV kleptomania of >or=1 year's duration. We excluded subjects with organic mental disorders, psychoses, substance or alcohol abuse, suicidal risk, bipolar I or II disorder, anorexia nervosa, or antisocial personality disorder and subjects requiring other psychotropic medications. Our primary outcome measure was theft episodes per week. A responder was defined as a subject having a > 50% decrease in theft episodes per week and a Clinical Global Impressions-Improvement scale score of "much improved" or "very much improved." Escitalopram was started at 10 mg/day and increased as necessary and tolerated after week 4 to 20 mg/day. At the end of week 7, responders were randomly assigned to a 1-week taper followed by 16 weeks of placebo or to continuation of treatment for 17 weeks at their week 7 escitalopram dose.Nineteen subjects (79%) were week 7 responders and 15 were randomly assigned. Five subjects (4 responders) withdrew early: 1 for unrelated illness, 1 for protocol deviation, 2 for side effects, and 1 for withdrawn consent. Three (43%) of 7 escitalopram subjects relapsed compared with 4 (50%) of 8 placebo subjects (Fisher exact test p = .38).The high response rate during open-label escitalopram treatment was not better maintained by double-blind escitalopram than by placebo. Kleptomania may be a heterogeneous pathological behavior better treated with pharma-cotherapy in some cases and psychologically or with combined treatment in others.

  View details for PubMedID 17388713

• Estimated prevalence of compulsive buying behavior in the United States AMERICAN JOURNAL OF PSYCHIATRY Koran, L. M., Faber, R. J., Aboujaoude, E., Large, M. D., Serpe, R. T. 2006; 163 (10): 1806-1812

  Abstract

  Compulsive buying (uncontrolled urges to buy, with resulting significant adverse consequences) has been estimated to affect from 1.8% to 16% of the adult U.S. population. To the authors' knowledge, no study has used a large general population sample to estimate its prevalence.The authors conducted a random sample, national household telephone survey in the spring and summer of 2004 and interviewed 2,513 adults. The interviews addressed buying attitudes and behaviors, their consequences, and the respondents' financial and demographic data. The authors used a clinically validated screening instrument, the Compulsive Buying Scale, to classify respondents as either compulsive buyers or not.The rate of response was 56.3%, which compares favorably with rates in federal national health surveys. The cooperation rate was 97.6%. Respondents included a higher percentage of women and people ages 55 and older than the U.S. adult population. The estimated point prevalence of compulsive buying among respondents was 5.8% (by gender: 6.0% for women, 5.5% for men). The gender-adjusted prevalence rate was 5.8%. Compared with other respondents, compulsive buyers were younger, and a greater proportion reported incomes under 50,000 US dollars. They exhibited more maladaptive responses on most consumer behavior measures and were more than four times less likely to pay off credit card balances in full.A study using clinically valid interviews is needed to evaluate these results. The emotional and functional toll of compulsive buying and the frequency of comorbid psychiatric disorders suggests that studies of treatments and social interventions are warranted.

  View details for Web of Science ID 000240906800026

  View details for PubMedID 17012693

• Potential markers for problematic Internet use: A telephone survey of 2,513 adults CNS SPECTRUMS Aboujaoude, E., Koran, L. M., Gamel, N., Large, M. D., Serpe, R. T. 2006; 11 (10): 750-755

  Abstract

  The Internet has positively altered many aspects of life. However, for a subset of users, the medium may have become a consuming problem that exhibits features of impulse control disorders recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.This is the first large-scale epidemiological study of problematic Internet use through a random-digit-dial telephone survey of 2,513 adults in the United States. Given the lack of validated criteria, survey questions were extrapolated from established diagnostic criteria for impulse control disorders, obsessive-compulsive disorder, and substance abuse. Four possible diagnostic criteria sets were generated. The least restrictive set required the respondent to report an unsuccessful effort to reduce Internet use or a history of remaining online longer than intended, Internet use interfering with relationships, and a preoccupation with Internet use when offline.The response rate was 56.3%. Interviews averaged 11.3 minutes in duration. From 3.7% to 13% of respondents endorsed > or =1 markers consistent with problematic Internet use. The least restrictive proposed diagnostic criteria set yielded a prevalence of problematic Internet use of 0.7%.Potential markers of problematic Internet use seem present in a sizeable proportion of adults. Future studies should delineate whether problematic Internet use constitutes a pathological behavior that meets criteria for an independent disorder, or represents a symptom of other psychopathologies.

  View details for PubMedID 17008818

• Pulse-loaded intravenous clomipramine in treatment-resistant obsessive-compulsive disorder JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Koran, L. M., Aboujaoude, E., Ward, H., Shapira, N. A., Sallee, F. R., Gamel, N., Elliott, M. 2006; 26 (1): 79-83

  Abstract

  Small studies have suggested that intravenous clomipramine (CMI) may be more effective and induce faster improvement in obsessive-compulsive disorder than do orally administered serotonin reuptake inhibitors.To test these hypotheses, we conducted a randomized, double-blind, double-dummy study of pulse-loaded intravenous versus oral CMI, followed by open-label oral CMI for 12 weeks.We enrolled a volunteer and referred group of 34 adults with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition obsessive-compulsive disorder of > or =1-year duration and Yale-Brown Obsessive Scale score of > or =20. Eligible subjects had failed > or =2 adequate serotonin reuptake inhibitor trials. Subjects received pulse loaded CMI 150 mg by vein or by mouth on day 1 and 200 mg on day 2. Oral CMI began on day 6 at 200 mg/d and was increased by 25 mg every 4 days to 250 mg/d, as tolerated, for 12 weeks.Adverse events led to one withdrawal during oral pulse loading and 5 during open-label oral treatment. Intravenous pulse loading did not induce a more rapid or greater Yale-Brown Obsessive Scale score decrease than oral pulse loading at day 6 or by week 12. Day 6 and week 12 improvement were unrelated to plasma drug or metabolite concentrations. Pulse loading itself seemed to induce more rapid and greater improvement than expected in treatment-resistant obsessive-compulsive disorder.Further investigation of oral pulse-loading regimens in treatment-resistant obsessive-compulsive disorder is warranted.

  View details for DOI 10.1097/01.jcp.0000195112.24769.b3

  View details for PubMedID 16415712

• High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: A multicenter double-blind tyial 40th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit Ninan, P. T., Koran, L. M., Kiev, A., Davidson, J. R., Rasmussen, S. A., Zajecka, J. M., Robinson, D. G., Crits-Christoph, P., Mandel, F. S., Austin, C. PHYSICIANS POSTGRADUATE PRESS. 2006: 15–22

  Abstract

  To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment.Sixty-six nonresponders to 16 weeks of sertraline treatment who met DSM-III-R criteria for current OCD were randomly assigned, in a double-blind continuation phase of a multicenter trial, either to continue on 200 mg/day of sertraline or to increase their dose to between 250 and 400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were collected from July 26, 1994, to October 26, 1995.The high-dose (250-400 mg/day, mean final dose = 357, SD = 60, N = 30) group showed significantly greater symptom improvement than the 200-mg/day group (N = 36) as measured by the YBOCS (p = .033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011). Responder rates (decrease in YBOCS score of > or = 25% and a CGI-I rating < or = 3) were not significantly different for the 200-mg/day versus the high-dose sertraline group, either on completer analysis, 34% versus 52%, or on endpoint analysis, 33% versus 40%. Both treatments showed similar adverse event rates.Greater symptom improvement was seen in the high-dose sertraline group compared to the 200-mg/day dose group during continuation treatment. Both dosages yielded similar safety profiles. Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment.

  View details for Web of Science ID 000235151000003

  View details for PubMedID 16426083

• Memantine for treatment-resistant OCD AMERICAN JOURNAL OF PSYCHIATRY Poyurovsky, M., Weizman, R., Weizman, A., Koran, L. 2005; 162 (11): 2191-2192

  View details for Web of Science ID 000232977600034

  View details for PubMedID 16263867

• Neurological soft signs as predictors of treatment response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES Hollander, E., Kaplan, A., Schmeidler, J., Yang, H. C., Li, D., Koran, L. M., Barbato, L. M. 2005; 17 (4): 472-477

  Abstract

  Neurological soft-sign abnormalities have been implicated in obsessive-compulsive disorder (OCD). This first comprehensive data analysis evaluated the association between baseline neurological soft signs and treatment response in 117 OCD patients treated with controlled-release fluvoxamine in a double-blind placebo-controlled trial. Total and right-sided soft signs for the responders and the nonresponders did not differ significantly. Left-sided visuospatial soft signs were significantly increased in treatment nonresponders compared to responders. These subtle neurological abnormalities may implicate a potential subgroup of OCD patients with poorer treatment response. This may have treatment implications and therefore serve as a screening tool in OCD.

  View details for Web of Science ID 000233966900005

  View details for PubMedID 16387985

• Obsessive-compulsive disorder (OCD) with schizotypy vs. schizophrenia with OCD: diagnostic dilemmas and therapeutic implications JOURNAL OF PSYCHIATRIC RESEARCH Poyurovsky, M., Koran, L. M. 2005; 39 (4): 399-408

  Abstract

  Although schizophrenia and obsessive-compulsive disorder (OCD) are distinct diagnostic entities, there are substantial areas of overlap between the two disorders in clinical characteristics, affected brain areas and pharmacotherapy. Though OCD patients apparently do not have increased risk for developing schizophrenia, schizotypal personality disorder has consistently been found in OCD patients. Compelling evidence also points to an increased rate of OCD in schizophrenia patients. Accurate diagnosis of both disorders in their "pure" and overlapping forms is necessary in order to evaluate etiological mechanisms underlying schizophrenia and OCD, and to provide adequate treatment and prognosis. In this review, we address some aspects of the current status of research pertinent to the OCD-schizophrenia interface and suggest further steps towards the clinical and etiological identification of homogeneous subgroups on the putative OCD-schizophrenia axis.

  View details for DOI 10.1016/j.jpsychires.2004.09.004

  View details for Web of Science ID 000230295900008

  View details for PubMedID 15804390

• Mirtazapine for obsessive-compulsive disorder: An open trial followed by double-blind discontinuation JOURNAL OF CLINICAL PSYCHIATRY Koran, L. M., Gamel, N. N., Choung, H. W., Smith, E. H., Aboujaoude, E. N. 2005; 66 (4): 515-520

  Abstract

  Many patients with obsessive-compulsive disorder (OCD) experience little response to standard treatment with serotonin reuptake inhibitors. Mirtazapine enhances serotonergic function by a mechanism distinct from reuptake inhibition. Because a pilot study suggested effectiveness of mirtazapine in OCD, we conducted a controlled trial.We recruited 30 subjects, 15 treatmentnaive and 15 treatment-experienced, with DSM-IV OCD of > or =1 year's duration and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of > or =20. In the 12-week, open-label phase, subjects received mirtazapine starting at 30 mg/day and titrated over 2 weeks as tolerated to 60 mg/day. At week 12, responders (YBOCS score decrease > 25%) were randomly assigned, double-blind, to continue mirtazapine or switch to placebo for 8 weeks, including a 1-week, double-blind taper week for placebo subjects.In the open-label phase, the mean +/-SD YBOCS score fell from 28.3 +/-3.7 to 20.3 +/-8.5 (paired samples t = 4.81, p < .0001). Four subjects (13.3%) discontinued for side effects. Sixteen subjects (53.3%) (8 treatmentnaive, 8 treatment-experienced) were responders and 15 agreed to randomization. Response was independent of comorbid mood disorders. In the 8-week, double-blind, placebo-controlled discontinuation phase, the mirtazapine group's mean YBOCS score fell a mean +/-SD of 2.6 +/-8.7 points while the placebo group's mean score rose a mean +/-SD of 9.1 +/-7.5 points (Mann Whitney U = 6.5, p = .005, 1-tailed). All other outcome measures were consistent with mirtazapine's superiority versus placebo.Mirtazapine may be an effective pharmacotherapy for OCD. If our results are replicated, larger double-blind studies would be indicated.

  View details for PubMedID 15816795

• Double-blind treatment with oral morphine in treatment-resistant obsessive-compulsive disorder JOURNAL OF CLINICAL PSYCHIATRY Koran, L. M., Aboujaoude, E., Bullock, K. D., Franz, B., Gamel, N., Elliott, M. 2005; 66 (3): 353-359

  Abstract

  Obsessive-compulsive disorder (OCD) often responds inadequately to serotonin reuptake inhibitors (SRIs). A case series reported substantial response to once-weekly oral morphine. We conducted a placebo-controlled, double-blind trial to investigate whether once-weekly oral morphine is effective in SRI-resistant OCD.Subjects with DSM-IV-defined OCD for > or =3 years who had failed > or =2 adequate SRI trials and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of > or =20 were recruited. Current medications were continued. Subjects were randomly assigned to random-order, 2-week blocks of once-weekly morphine, lorazepam, and placebo. Week 2 dosage was increased, decreased, or maintained depending on response and side effects.We enrolled 23 subjects, who had failed 2 to 6 SRI trials. The median screening Y-BOCS score was 29. The median Y-BOCS score after morphine (highest dose) was 25 (median decrease = 13%). Seven subjects (30%) were responders (Y-BOCS decreases > or =25%). The median Y-BOCS score after lorazepam (highest dose) was 27 (median decrease = 6%). Four subjects (17%) responded to lorazepam; 1 was a morphine responder. The median Y-BOCS score after placebo (highest dose) was 27 (median decrease = 7%), and no subject responded. Responses differed significantly among the 3 conditions (Friedman 2-way analysis of variance, chir(2) = 13.92, df = 2, p = .01). Wilcoxon matched-pairs signed-rank tests (T = 56.5, p = .05) showed significance for morphine versus placebo but not lorazepam versus placebo.Our results support the hypothesis that once-weekly oral morphine can reduce symptoms in some treatment-resistant OCD patients. The mechanism of action is unknown. Further studies of mu-agonists and glutamate antagonists are warranted.

  View details for PubMedID 15766302

• Quetiapine augmentation in obsessive-compulsive disorder resistant to serotonin reuptake inhibitors: An open-label study JOURNAL OF CLINICAL PSYCHIATRY Bogan, A. M., Koran, L. M., Chuong, H. V., Vapnik, T., Bystritsky, A. 2005; 66 (1): 73-79

  Abstract

  The response of obsessive-compulsive disorder (OCD) to serotonin reuptake inhibitors (SRIs) is often inadequate. Case series reporting successful augmentation with risperidone and olanzapine led us to investigate quetiapine in OCD that was resistant to SRI treatment.In this 8-week, 2-site (S1, S2), open-label trial, 30 adults (16 at S1 and 14 at S2) with a DSM-IV diagnosis of OCD, SRI-resistant, received augmentation with quetiapine, with the dose doubled every 2 weeks from 25 mg to 200 mg/day. Primary outcome was measured with the Yale-Brown Obsessive Compulsive Scale (YBOCS). A response was defined as a > or = 25% decrease from the baseline YBOCS score.Significant differences between the sites in patient characteristics (7/14 at S2 were hoarders, i.e., more treatment resistant, vs. 1/16 at S1; p = .01) and in quetiapine treatment (mean +/- SD dose of 116 +/- 72 mg/day at S2 vs. 169 +/- 57 mg/day at S1; p = .039) necessitated separate analysis of results. At S1, the mean +/- SD YBOCS score fell significantly from 27.7 +/- 7.0 to 23.3 +/- 8.4 (t = 2.96, df = 15, p = .01), and the responder rate was 31% (5/16). At S2, the mean YBOCS score did not decrease significantly, and the responder rate was 14% (2/14). Most adverse medication events were mild or moderate. Two subjects (13%) at S1 and 3 (21%) at S2 withdrew due to adverse events.The results at S1 resemble those reported with other atypical antipsychotics and suggest that quetiapine augmentation may benefit treatment-resistant OCD. The poorer results at S2 may reflect the large proportion of hoarders or the less intense treatment. Longer, higher dose, large, double-blind, placebo-controlled comparison trials of atypical antipsychotics are needed.

  View details for Web of Science ID 000226493200010

  View details for PubMedID 15669891

• A case of kleptomania correlating with premenstrual dysphoria JOURNAL OF CLINICAL PSYCHIATRY Aboujaoude, E., Gamel, N., Koran, L. M. 2004; 65 (5): 725-726

  View details for Web of Science ID 000221887100025

  View details for PubMedID 15163267

• Overview of Kleptomania and Phenomenological Description of 40 Patients. Primary care companion to the Journal of clinical psychiatry Aboujaoude, E., Gamel, N., Koran, L. M. 2004; 6 (6): 244-247

  Abstract

  BACKGROUND: Despite its considerable personal toll and its impact on the economy and the legal system, kleptomania is an understudied psychiatric disorder. METHOD: We review what is known about the epidemiology, course, and treatment of kleptomania and describe 40 patients meeting DSM-IV criteria for the disorder. RESULTS: Our data suggest a female preponderance, with an early age at onset and most often a continuous course. No other gender-based differences were seen. The majority of our subjects had not received treatment for kleptomania despite often having sought help for comorbid psychiatric conditions, most commonly major depressive disorder. Our data confirm kleptomania's devastating effects on personal and professional lives and serious legal consequences, reflected in high arrest and incarceration rates. Because patients with kleptomania rarely seek psychiatric help for the disorder, we indicate how other health care providers can screen for it, possibly as part of taking patients' legal and social histories, and suggest treatments. CONCLUSION: Awareness of kleptomania, empathy toward those afflicted, and rigorous research into treatment options are needed to mitigate kleptomania's personal and societal costs.

  View details for PubMedID 15614312

• Serotonin-1D hypothesis of obsessive-compulsive disorder: An update 6th International Obsessive-Compulsive Disorder Conference Zohar, J., Kennedy, J. L., Hollander, E., Koran, L. M. PHYSICIANS POSTGRADUATE PRESS. 2004: 18–21

  Abstract

  Support for the serotonin-1D (5-HT(1D)) hypothesis of obsessive-compulsive disorder (OCD) and related conditions comes from a variety of sources. Some pharmacologic challenges with the 5-HT(1D) agonist sumatriptan, and case reports in which prolonged administration of 5-HT(1D) agonists was associated with a therapeutic effect, suggest that 5-HT(1D) may play a role in obsessive-compulsive symptoms. Genetic studies have also found that polymorphism of the 5-HT(1D) gene may be preferentially transmitted to those patients with OCD. However, taking into account that OCD is a heterogeneous syndrome, the 5-HT(1D) hypothesis requires further investigation in order to disentangle the role of the 5-HT(1D) receptor in this common and often severe disorder.

  View details for Web of Science ID 000225732300004

  View details for PubMedID 15554784

• A 1-year naturalistic follow-up of patients with compulsive shopping disorder JOURNAL OF CLINICAL PSYCHIATRY Aboujaoude, E., Gamel, N., Koran, L. M. 2003; 64 (8): 946-950

  Abstract

  Compulsive shopping disorder is increasingly recognized as a treatable impulse-control disorder. We report the first long-term, naturalistic follow-up of patients with compulsive shopping disorder, which examined the course of illness over 1 year in a cohort that had completed up to 3 months of open-label treatment with citalopram, 20 mg/day to 60 mg/day. In that trial, 17 (71%) of 24 subjects who met McElroy and colleagues' diagnostic criteria for compulsive shopping disorder were responders (Clinical Global Impressions-Improvement scale rating of much or very much improved and Yale-Brown Obsessive Compulsive Scale-Shopping Version score decrease of >/= 50%).Follow-up interviews occurred 3, 6, 9, and 12 months after study end. Data gathered included comorbid conditions, estimated total debt, 2-week spending, whether the patient was taking citalopram, and illness versus remission status. Remission was defined as no longer meeting diagnostic criteria for compulsive shopping disorder. Data were gathered between March 2000 and January 2002.Of responders at trial end, 81% (13/16), 71% (10/14), 71% (10/14), and 73% (11/15) were in remission at 3, 6, 9, and 12 months. Mean 2-week compulsive shopping expenditures decreased from 773 US dollars (median = 500 US dollars) at baseline to 351 US dollars (median = 0 US dollars) at month 12, and mean total debt decreased from 17,833 US dollars (median = 20,000 US dollars) to 16,752 US dollars (median = 14,000 US dollars). No clear association was seen between taking citalopram and remission status (p =.55, p =.08, p =.58, and p =.60 at 3, 6, 9, and 12 months, respectively; Fisher exact test). The majority of trial nonresponders remained ill at each follow-up point.An acute response to citalopram predicts a greater likelihood of continued remission over 1 year, although the mechanisms that maintain remission require further investigation.

  View details for PubMedID 12927011

• Citalopram for compulsive shopping disorder: An open-label study followed by double-blind discontinuation 40th Annual Meeting of the American-College-of-Neuropsychopharmacology Koran, L. M., Chuong, H. W., Bullock, K. D., Smith, S. C. PHYSICIANS POSTGRADUATE PRESS. 2003: 793–98

  Abstract

  Open-label trials suggested that fluvoxamine and citalopram may be effective for compulsive shopping disorder, but 2 double-blind fluvoxamine trials failed to confirm this. To test the hypothesis that citalopram is a safe, effective treatment for this disorder, we conducted a 7-week, open-label trial followed by a 9-week, double-blind, placebo-controlled discontinuation trial.From Jan. 2001 to Jan. 2002, we enrolled adult outpatients meeting diagnostic criteria suggested in a prior study for compulsive shopping disorder and having a score of >/= 17 on the Yale-Brown Obsessive Compulsive Scale-Shopping Version (YBOCS-SV). Open-label citalopram was started at 20 mg/day and increased, absent marked response and limiting side effects, to 60 mg/day. Responders (subjects rated "much improved" or "very much improved" on the Clinical Global Impressions-Improvement scale [CGI-I] and having a >/= 50% decrease in YBOCS-SV score) were randomized to double-blind citalopram treatment at the week 7 dose or placebo for 9 weeks.We enrolled 24 subjects (23 women and 1 man). Mean +/- SD YBOCS-SV scores decreased significantly from 24.3 +/- 4.6 at baseline to 8.2 +/- 8.1 at week 7 (Wilcoxon signed rank: z = 4.20, p <.001). Fifteen of 24 subjects (63%) met the responder criteria. Three subjects (13%) discontinued for adverse events (1 each for headache, rash, and insomnia). Of the 15 responders who entered the double-blind treatment phase, 5 of 8 (63%) randomized to placebo relapsed (YBOCS-SV score >/= 17 and "minimally improved" or less on the CGI-I) compared with none of 7 randomized to continue taking citalopram (Fisher exact test p =.019).Citalopram appears to be a safe and effective treatment for compulsive shopping disorder. Further trials of citalopram and other selective serotonin reuptake inhibitors are warranted.

  View details for Web of Science ID 000184233600009

  View details for PubMedID 12934980

• A double-blind, placebo-controlled study of the efficacy and safety of controlled-release fluvoxamine in patients with obsessive-compulsive disorder JOURNAL OF CLINICAL PSYCHIATRY Hollander, E., Koran, L. M., Goodman, W. K., Greist, J. H., Ninan, P. T., Yang, H. C., Li, D., Barbato, L. M. 2003; 64 (6): 640-647

  Abstract

  The aim of this 12-week, double-blind, flexible-dose, placebo-controlled, parallel-arm, multicenter trial was to determine the safety and efficacy of fluvoxamine in a controlled-release (CR) formulation in adult outpatients with obsessive-compulsive disorder (OCD).253 adult outpatients with DSM-IV OCD were randomly assigned to receive 100 to 300 mg of fluvoxamine CR (N = 127) or placebo (N = 126) once daily for 12 weeks. Intent-to-treat analyses of efficacy assessments with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I) were conducted.Fluvoxamine CR was significantly (p <.05) superior to placebo in decreasing YBOCS total score beginning at week 2. This early response was sustained at all subsequent visits. At endpoint, there was a mean decrease of 8.5 +/- 0.7 (31.7%) in the YBOCS total score compared with baseline in the fluvoxamine CR treatment group versus a mean decrease of 5.6 +/- 0.7 (21.2%) in the placebo group (p =.001). Fluvoxamine CR was also significantly superior to placebo in lowering the severity of illness (CGI-S, p =.002) and in producing clinical improvement (CGI-I, p <.01). At endpoint, significantly greater percentages of the fluvoxamine CR treatment group were responders (p =.002) and remitters (p =.019) compared with the placebo group.Over 12 weeks, fluvoxamine CR treatment was associated with a statistically significant and clinically relevant reduction in OCD severity and was found to be safe and well tolerated. The early onset of therapeutic effect, starting from week 2, was of particular interest.

  View details for Web of Science ID 000183746400004

  View details for PubMedID 12823077

• Venlafaxine in treatment-resistant obsessive-compulsive disorder JOURNAL OF CLINICAL PSYCHIATRY Hollander, E., Friedberg, J., WASSERMAN, S., Allen, A., BIRNBAUM, M., Koran, L. M. 2003; 64 (5): 546-550

  Abstract

  While selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of obsessive-compulsive disorder (OCD), approximately 40% of patients fail to respond to SSRIs. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that might be effective in the treatment of OCD, even among those who have failed previous SSRI trials.Thirty-nine patients who met DSM-IV criteria for OCD, including 29 who were resistant to prior SRI treatment trials, were treated with venlafaxine in an open, naturalistic fashion. Improvement was assessed using the Clinical Global Impressions-Improvement scale.Of 39 patients treated with venlafaxine, 27 (69.2%) were rated as sustained treatment responders. Of the 29 patients who did not respond to 1 or more previous SRI trials, 22 (75.9%) were rated as having sustained response to treatment. Mean dose of venlafaxine was 232.2 mg/day (range, 37.5-375 mg/day), and it was generally well tolerated.Venlafaxine may be beneficial to individuals with OCD, including those who have not responded to prior SSRI trials. However, these findings must be interpreted with caution, as the study is limited by its open, retrospective nature and its inclusion of patients with comorbid diagnoses and patients on concomitant medications. Prospective, controlled trials with a more homogeneous patient population are needed to replicate these preliminary findings.

  View details for Web of Science ID 000183114500008

  View details for PubMedID 12755657

• Venlafaxine in treatment-resistant obsessive-compulsive disorder 58th Annual Convention of the Society-of-Biological-Psychiatry Hollander, E., Friedberg, J., WASSERMAN, S., Allen, A., Koran, L. M., BIRNBAUM, M. ELSEVIER SCIENCE INC. 2003: 206S–207S

  View details for Web of Science ID 000182436000569

• Continuation treatment of chronic depression: a comparison of nefazodone, cognitive behavioral analysis system of psychotherapy, and their combination. Psychopharmacology bulletin Kocsis, J. H., Rush, A. J., Markowitz, J. C., Borian, F. E., Dunner, D. L., Koran, L. M., Klein, D. N., Trivedi, M. H., Arnow, B., Keitner, G., Kornstein, S. G., Keller, M. B. 2003; 37 (4): 73-87

  Abstract

  Little is known about the relative benefits of psychotherapy, medication, and combined treatment as continuation therapies for chronic forms of major depressive disorder (MDD) after a positive response to acute treatment. We hypothesize that combined treatment would demonstrate superior continuation phase outcomes compared to either monotherapy, as evidenced by lower relapse rates and greater rates of improvement from partial to full remission. We report 16-week continuation phase outcomes for 324 patients who had participated in either the acute phase of a randomized multicenter trial of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combination therapy (COMB) for chronic forms of MDD. Patients entering the continuation phase had either fully or partially remitted after 12 weeks of acute phase treatment. The primary efficacy measure was the 24-item Hamilton Rating Scale for Depression. For patients in remission at acute phase exit, 73.3% (107/146) maintained their remitted status at endpoint of the continuation phase. Of those having a partial remission at acute phase exit, 52.9% (92/174) achieved full remission by end of continuation. A greater proportion of patients maintained a partial or full remission status on COMB (90%) compared to nefazodone (80%, p=0.011) or to CBASP (82%, p=0.042). These differences reflected greater symptom re-emergence in the partial remission groups on CBASP and nefazodone monotherapy compared to COMB. Continuation treatment assignment was not randomized or blinded. There was no placebo group. Most patients with chronic forms of MDD sustained their acute phase response and more than 50% of partial remitters achieved full remission while continuing treatment with nefazodone, CBASP, or COMB. COMB was associated with less symptom re-emergence during the continuation phase than either monotherapy, particularly for partial remitters.

  View details for PubMedID 15131518

• Medical disorders among patients admitted to a public-sector psychiatric inpatient unit PSYCHIATRIC SERVICES Koran, L. M., Sheline, Y., Imai, K., Kelsey, T. G., Freedland, K. E., Mathews, J., Moore, M. 2002; 53 (12): 1623-1625

  Abstract

  Active and important physical disorders are common among public-sector psychiatric patients and are frequently undetected. A total of 289 patients who were consecutively admitted to a public psychiatric hospital were screened for physical disorders and given medical evaluations when screening results suggested an active and important physical disorder. Twenty-nine percent of the patients had such disorders. Of the 119 disorders detected, 24 (20 percent) were newly diagnosed for 23 patients (8 percent). Physical disorders that may have caused or exacerbated patients' psychiatric symptoms affected 2 percent and 3.5 percent of the patients, respectively. Patients admitted to psychiatric inpatient units should be carefully evaluated for physical disease.

  View details for Web of Science ID 000179620900022

  View details for PubMedID 12461226

• Citalopram for compulsive shopping disorder: A double-blind study Koran, L. M., Chuong, H. W., Bullock, K. D., Smith, S. C. ELSEVIER SCIENCE BV. 2002: S411–S412

  View details for Web of Science ID 000178905000700

• Citalopram intravenous infusion in resistant obsessive-compulsive disorder: An open trial JOURNAL OF CLINICAL PSYCHIATRY Pallanti, S., Quercioli, L., Koran, L. M. 2002; 63 (9): 796-801

  Abstract

  Treatment with intravenous clomipramine is rapidly effective in some obsessive-compulsive disorder (OCD) patients unresponsive to orally administered serotonin reuptake inhibitors (SRIs). The selective serotonin reuptake inhibitor citalopram is effective for OCD when administered orally. We investigated whether intravenous citalopram would rapidly benefit OCD patients unresponsive to orally administered SRIs.Thirty-nine adult outpatients participated in a 3-week open-label trial of intravenous citalopram. Eligible patients had moderate-to-severe DSM-IV OCD of > or = 1 year's duration, a baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) score > or = 25, and no other active Axis I diagnosis and had failed at least 2 adequate oral SRI trials, excluding citalopram. Intravenous citalopram was administered daily for 21 days, followed by oral citalopram until treatment day 84. Intravenous citalopram was started at 20 mg/day and was increased to 40 to 80 mg/day as tolerated.Intravenous citalopram was well tolerated even at higher doses (dropout rate = 2.6%). At day 21, 23 (59%) of the 39 patients had YBOCS score decreases of > or = 25%, of whom 4 had decreases of > or = 35%. Twenty-seven patients with YBOCS score decreases of > or = 20% were allowed to continue on treatment with oral citalopram, and by day 84, all had substantial further improvement. All 27 patients also showed significant improvement in several dimensions of quality of life.Intravenous citalopram was safe and rapidly effective in a group of treatment-resistant OCD patients. The early onset of response suggests a means of accelerating OCD symptom relief and predicting response to oral citalopram treatment. Double-blind, double-dummy, placebo-controlled trials of intravenous versus oral citalopram in patients with treatment-resistant OCD are indicated.

  View details for Web of Science ID 000178344600008

  View details for PubMedID 12363120

• Citalopram treatment of compulsive shopping: An open-label study 41st Annual Meeting of the New-Clinical-Drug-Evaluation-Unit Koran, L. M., Bullock, K. D., Hartston, H. J., Elliott, M. A., D'Andrea, V. PHYSICIANS POSTGRADUATE PRESS. 2002: 704–8

  Abstract

  Compulsive shopping, a DSM-IV impulse-control disorder not otherwise specified, is characterized by preoccupation with shopping and inability to resist buying unneeded items, with resulting marked distress, social or occupational impairment, and financial and/or familial problems. Because an open-label trial suggested that fluovaxamine, a selective serotonin reuptake inhibitor (SSRI), is effective for this disorder, we tested the effectiveness of the SSRI citalopram.We enrolled adults meeting formal diagnostic criteria (as defined by McElroy and colleagues) in a 12-week open-label trial. We excluded subjects with obsessive-compulsive disorder, bipolar disorder, substance abuse or dependence, or psychotic disorders. Citalopram treatment was begun at 20 mg/day and increased every 2 weeks by 20 mg/day, absent marked response and limiting side effects, to 60 mg/day. At endpoint, all subjects were asked to give written informed consent for follow-up telephone interviews at 3-month intervals for 12 months.We enrolled 24 subjects, 22 women and 2 men, whose mean +/- SD age was 43.7 +/- 8.1 years; most had been shopping compulsively for 2 decades or more. Citalopram (mean +/- SD endpoint dose = 35.4 +/- 21.4 mg/day) produced rapid, marked, sustained improvements on both the Yale-Brown Obsessive Compulsive Scale-Shopping Version and the Clinical Global Impressions-Improvement (CGI-I) scale in subjects with and without comorbid conditions. Seventeen subjects (71%) were responders, achieving ratings of much or very much improved on the CGI-I, including 2 of the 3 subjects who discontinued for adverse events (sedation or agitation). During a 6-month follow-up period, those continuing citalopram therapy were less likely to relapse than those discontinuing the medication.Citalopram appears to be a safe and effective treatment for compulsive shopping. Acute and long-term, double-blind, placebo-controlled trials of citalopram and other SSRIs for the treatment of this disorder are indicated.

  View details for PubMedID 12197451

• Treatment non-response in OCD: methodological issues and operational definitions INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY Pallanti, S., Hollander, E., Bienstock, C., Koran, L., Leckman, J., Marazziti, D., Pato, M., Stein, D., Zohar, J. 2002; 5 (2): 181-191

  Abstract

  While controlled trials with SRIs have demonstrated a selective efficacy in obsessive-compulsive disorder (OCD), up to 40-60% of patients do not have a satisfactory outcome. Non-response to treatment in OCD is associated with serious social disability. There are a large number of non-responsive patients, and they are difficult to cluster due to ambiguities in the diagnostic criteria, possibility of subtypes, and a high rate of comorbidity. Moreover, the findings of current studies of so-called 'non-responsive' cases are currently non-generalizable because of the lack of an operational definition of non-response. The result has been that a cumulative body of data on a reasonably homogeneous sample of non-responders has not been developed. The aims of this paper are to clarify some of the obstacles in defining stages of response and levels of non-response and, through a comprehensive analysis, to propose a systematic nosology for this rather common condition. Better characterization of which patients respond and do not respond to various treatments will enable more accurate clustering of patients, and help facilitate multi-site data collection for future research trials.

  View details for DOI 10.1017/S1461145702002900

  View details for Web of Science ID 000176657300009

  View details for PubMedID 12135542

• Impulsive behavior in a consumer culture INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE Hartston, H. J., Koran, L. M. 2002; 6 (2): 65-68

  View details for Web of Science ID 000175930500002

• Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression ARCHIVES OF GENERAL PSYCHIATRY Thase, M. E., Rush, A. J., Howland, R. H., Kornstein, S. G., Kocsis, J. H., Gelenberg, A. J., Schatzberg, A. F., Koran, L. M., Keller, M. B., Russell, J. M., Hirschfeld, R. M., LaVange, L. M., Klein, D. N., Fawcett, J., Harrison, W. 2002; 59 (3): 233-239

  Abstract

  Although various strategies have been proposed to treat antidepressant nonresponders, little controlled research has been published that examines prospectively the use of switching to an alternate antidepressant.This was a multisite study in which outpatients with chronic major depression (with or without concurrent dysthymia), who failed to respond to 12 weeks of double-blind treatment with either sertraline hydrochloride (n = 117) or imipramine hydrochloride (n = 51), were crossed over or switched to 12 additional weeks of double-blind treatment with the alternate medication. Outcome measures included the 24-item Hamilton Rating Scale for Depression and the Clinical Global Impressions--Severity and Improvement scales.The switch from sertraline to imipramine (mean dosage, 221 mg/d) and from imipramine to sertraline (mean dosage, 163 mg/d) resulted in clinically and statistically significant improvements. The switch to sertraline treatment was associated with fewer adverse effect complaints and significantly less attrition owing to adverse effects. Although sertraline treatment also resulted in significantly higher response rates in the intent-to-treat samples (60% in the sertraline group and 44% in the imipramine group), neither the intent-to-treat remission rates nor the response and remission rates among study completers differed significantly. Moreover, after considering the effect of attrition, there were no significant treatment effects on the more comprehensive generalized estimating equation analyses of the continuous dependent measures.More than 50% of chronically depressed antidepressant nonresponders benefited from a switch from imipramine to sertraline, or vice versa, despite a high degree of chronicity. As in the initial trial, sertraline was generally better tolerated than imipramine. Switching to a standard antidepressant of a different class is a useful treatment strategy for antidepressant nonresponders and could be considered a standard of comparison for future studies of novel alternate strategies.

  View details for Web of Science ID 000174300800004

  View details for PubMedID 11879161

• Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination BIOLOGICAL PSYCHIATRY Hirschfeld, R. M., Dunner, D. L., Keitner, G., Klein, D. N., Koran, L. M., Kornstein, S. G., Markowitz, J. C., Miller, I., Nemeroff, C. B., Ninan, P. T., Rush, A. J., Schatzberg, A. F., Thase, M. E., Trivedi, M. H., Borian, F. E., Crits-Christoph, P., Keller, M. B. 2002; 51 (2): 123-133

  Abstract

  Although it is known that antidepressant treatment improves psychosocial functioning, whether such changes occur independent of depressive symptoms is not known. This study compared efficacy of nefazodone, psychotherapy, and their combination in improving psychosocial functioning in chronically depressed outpatients.Patients with chronic forms of major depressive disorder were randomized to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. Psychosocial assessments measured overall psychosocial functioning, work functioning, interpersonal functioning, and general health.Relative to community norms, patients with chronic major depression evidenced substantially impaired psychosocial functioning at baseline. Combined treatment produced significantly greater psychosocial improvement than either CBASP alone or nefazodone alone on all primary measures. Combined treatment remained superior to nefazodone on primary measures of work, social, and overall functioning, and superior to CBASP on social functioning when depressive symptoms were controlled. Unlike the two groups receiving nefazodone, CBASP alone's effect on psychosocial function was relatively independent of symptom change. Psychosocial functioning improved more slowly than depressive symptoms, and moderate psychosocial impairments remained at end point.Combined treatment had greater effect than either monotherapy. Change in depressive symptoms did not fully explain psychosocial improvement. Moderate residual psychosocial impairment remained, suggesting the need for continuation/maintenance treatment.

  View details for Web of Science ID 000173570900001

  View details for PubMedID 11822991

• Refractory obsessive-compulsive disorder: State-of-the-art treatment 5th International Obsessive-Compulsive Disorder Conference Hollander, E., Bienstock, C. A., Koran, L. M., Pallanti, S., Marazziti, D., Rasmussen, S. A., Ravizza, L., Benkelfat, C., Saxena, S., Greenberg, B. D., Sasson, Y., Zohar, J. PHYSICIANS POSTGRADUATE PRESS. 2002: 20–29

  Abstract

  Nonresponse to treatment in obsessive-compulsive disorder is common, associated with substantial impairment, and understudied. Little practical advice is available to clinicians on next-step treatment strategies for patients who have not responded well to 2 trials of selective serotonin reuptake inhibitors (SSRIs). Available options include continuation of SSRI treatment, switching to another SSRI or selective serotonin-norepinephrine reuptake inhibitor, augmenting with atypical neuroleptics or cognitive-behavioral therapy, or utilizing novel treatment approaches. The authors synthesize state-of-the-art treatment and give practical advice for clinicians.

  View details for Web of Science ID 000175324500005

  View details for PubMedID 12027116

• Efficacy of sertraline in the long-term treatment of obsessive-compulsive disorder 39th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit Koran, L. M., Hackett, E., Rubin, A., Wolkow, R., Robinson, D. AMER PSYCHIATRIC PUBLISHING, INC. 2002: 88–95

  Abstract

  Obsessive-compulsive disorder (OCD) typically begins early in life and has a chronic course. Despite the need for long-term treatment, the authors found no placebo-controlled studies that have examined the relapse-prevention efficacy of maintenance therapy.Patients who met criteria for response after 16 and 52 weeks of a single-blind trial of sertraline were randomly assigned to a 28-week double-blind trial of 50-200 mg/day of sertraline or placebo. Primary outcomes after the double-blind trial were full relapse, dropout due to relapse or insufficient response, or acute exacerbation of OCD symptoms.Of 649 patients at baseline, 232 completed 52 weeks of the single-blind trial and met response criteria. Among the 223 patients in the double-blind phase of the study, sertraline had significantly greater efficacy than placebo on two of three primary outcomes: dropout due to relapse or insufficient clinical response (9% versus 24%, respectively) and acute exacerbation of symptoms (12% versus 35%). Sertraline resulted in improvement in quality of life during the initial 52-week trial and continued improvement, significantly superior to placebo, during the subsequent 28-week double-blind trial. Long-term treatment with sertraline was well tolerated. Over the entire study period, less than 20% of the patients stopped treatment because of adverse events.Sertraline demonstrated sustained efficacy among patients responding to treatment and was generally well tolerated during the 80-week study. During the study's last 28 weeks, sertraline demonstrated greater efficacy than placebo in preventing dropout due to relapse or insufficient clinical response and acute exacerbation of OCD symptoms.

  View details for Web of Science ID 000173079200017

  View details for PubMedID 11772695

• The prevalence of clinically recognized obsessive-compulsive disorder in a large health maintenance organization AMERICAN JOURNAL OF PSYCHIATRY Fireman, B., Koran, L. M., Leventhal, J. L., Jacobson, A. 2001; 158 (11): 1904-1910

  Abstract

  Little is known about the prevalence of obsessive-compulsive disorder (OCD) as recognized in clinical settings. The authors report data on the prevalence of clinically recognized OCD in a large, integrated, group practice health maintenance organization (HMO).The authors examined the database of outpatient diagnoses for the 1.7 million people (age >or=6) in the San Francisco Bay Area and Sacramento who were continuously enrolled in Kaiser Permanente from May 1995 through April 1996. OCD diagnoses were confirmed by chart review.The 1-year prevalence of clinically recognized OCD was 84/100,000 (95% confidence interval: 80-89/100,000), or 0.084%. It varied among the 19 clinics within the HMO but was nowhere higher than 150/100,000. Prevalence was higher among women than among men but was higher among boys than among girls. Above age 65, OCD prevalence decreased markedly in both genders. Period prevalence rates increased by 60% as the length of the study period doubled from 1 to 2 years, more than would be expected for a chronic disease requiring regular care. About three-quarters of both children and adults with OCD had comorbid psychiatric diagnoses; major depression was common in both groups.Although previously reported prevalences of 1%-3% from community studies may have included many transient or misclassified cases of OCD not requiring treatment, the very low prevalence of clinically recognized OCD in this population suggests that many individuals suffering from OCD are not receiving the benefits of effective treatment.

  View details for Web of Science ID 000171946300020

  View details for PubMedID 11691699

• Mirtazapine treatment of obsessive-compulsive disorder JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Koran, L. M., Quirk, T., Lorberbaum, J. P., Elliott, M. 2001; 21 (5): 537-539

  View details for Web of Science ID 000171341500016

  View details for PubMedID 11593084

• Fluoxetine in pathologic skin-picking - Open-label and double-blind results PSYCHOSOMATICS Bloch, M. R., Elliott, M., Thompson, H., Koran, L. M. 2001; 42 (4): 314-319

  Abstract

  Various studies suggest that selective serotonin reuptake inhibitors (SSRIs) may be useful in treating pathologic skin-picking. The authors investigated the effectiveness of fluoxetine in treating this behavior. Fifteen subjects with clinically significant skin-picking were recruited by newspaper advertisement. They received 6 weeks of open-label treatment with fluoxetine. Responders were then randomized to 6 weeks of double-blind fluoxetine or placebo. Treatment effect was assessed with standardized rating scales. All 15 subjects completed open-label treatment, and 8 were responders. Of these eight, the four randomized to double-blind fluoxetine maintained clinically significant improvement. The four randomized to placebo returned to their baseline symptom level. Larger studies are needed to determine which individuals are likely to respond to fluoxetine and the relative effectiveness of fluoxetine, other SSRIs, and other forms of treatment.

  View details for Web of Science ID 000170097400003

  View details for PubMedID 11496020

• Sertraline versus imipramine to prevent relapse in chronic depression JOURNAL OF AFFECTIVE DISORDERS Koran, L. M., Gelenberg, A. J., Kornstein, S. G., Howland, R. H., Friedman, R. A., Debattista, C., Klein, D., Kocsis, J. H., Schatzberg, A. F., Thase, M. E., Rush, A. J., Hirschfeld, R. M., LaVange, L. M., Keller, M. B. 2001; 65 (1): 27-36

  Abstract

  Chronic depressions are common, disabling and under-treated, and long-term treatment is little studied. We report the continuation phase results from a long-term treatment study.After 12 weeks of acute phase treatment in a double-blind, randomized, parallel-group, multi-center trial of sertraline or imipramine, patients with chronic depression (> or = 2 years in major depression, or major depression superimposed on dysthymia) continued study drug for 16 weeks. Initially, 635 patients were randomized to sertraline or imipramine in a 2:1 ratio. Nonresponders after 12 weeks entered a 12-week double-blind crossover trial of the alternate medication. Entry into continuation treatment required at least a satisfactory response (partial remission) to initial or crossover treatment.Of 239 acute or crossover responders to sertraline, 60% entered continuation in full remission and 40% with a partial remission. These proportions were identical for imipramine patients (n = 147). For both drug groups, over two-thirds of those entering in full remission retained it. For those entering in partial remission, over 40% achieved full remission. Patients requiring crossover treatment were less likely to maintain or improve their response during continuation treatment. The two drugs did not differ significantly in response distribution, drop out rates or discontinuation due to side effects during continuation treatment.The absence of a placebo group constrains interpretation of our results, but chronic depressions have low placebo response rates.Most chronic depression patients who remit with 12 weeks of sertraline or imipramine treatment maintain remission during 16 weeks of continuation treatment. Most patients with a satisfactory therapeutic response (partial remission) after 12 weeks of treatment maintain it or further improve. Patients treated with imipramine experienced more side effects, but both drugs were well tolerated.

  View details for Web of Science ID 000168910100005

  View details for PubMedID 11426506

• Sumatriptan, 5-MT1D receptors and obsessive-compulsive disorder EUROPEAN NEUROPSYCHOPHARMACOLOGY Koran, L. M., Pallanti, S., Quercioli, L. 2001; 11 (2): 169-172

  Abstract

  After considering the effects of 5-HT receptor agonists with different binding profiles on the symptoms of obsessive-compulsive disorder (OCD), Zohar and Kindler hypothesized that the 5-HT(1D) receptor was implicated in this disorder's pathophysiology.We explored the 5-HT(1D) hypothesis in a 5-day, random, double-blind, placebo-controlled trial of oral sumatriptan 100 mg/day in medication-free adults with OCD. We hypothesized that sumatriptan, a 5-HT(1D) agonist, would diminish 5-HT release, thereby worsening OCD symptoms. We further hypothesized that by beginning to desensitize 5-HT(1D) receptors, sumatriptan pretreatment would promote a faster response or an increased likelihood of response to subsequent treatment with a selective serotonin reuptake inhibitor.The five sumatriptan subjects' OCD symptom worsening, as measured by the Yale-Brown scale ( upward arrow 17.6% (S.D. 14.6)), was significant when compared to the slight symptom decrease in the five placebo subjects ( downward arrow 5.2% (S.D. 4.9), P<0.015). The sumatriptan group did not exhibit a faster response or greater likelihood of response to a 90-day, open label trial of paroxetine.Longer term studies of the effects of 5-HT(1D) agonists on OCD symptoms are indicated. Zolmitriptan, a potent 5-HT(1D) receptor agonist with better penetration of the blood-brain barrier, may be a preferred challenge agent.

  View details for Web of Science ID 000168399600012

  View details for PubMedID 11313163

• Effect of concurrent anxiety on response to sertraline and imipramine in patients with chronic depression DEPRESSION AND ANXIETY Russell, J. M., Koran, L. M., Rush, J., Hirschfeld, R. M., Harrison, W., Friedman, E. S., Davis, S., Keller, M. 2001; 13 (1): 18-27

  Abstract

  Anxiety commonly complicates the clinical presentation of depression and has been associated with poorer long-term outcome, but little information is available on the clinical correlates, and comparative effect on treatment response, of subsyndromic or secondary anxiety. Patients diagnosed with chronic major or double depression were randomized to 12 weeks of double-blind treatment with either sertraline or imipramine in a 2:1 ratio. A high anxiety subgroup was operationally defined by a HAM-D anxiety/somatization factor score > or = 7. The effect of study treatment was measured utilizing the HAM-D, CGI, HAM-D anxiety/somatization factor, as well as a quality of life measure (Q-LES-Q) and a measure of psychosocial functioning (the MOS-SF-36). Two hundred nine patients were treated with imipramine and 426 patients were treated with sertraline. Thirty-six percent of the total met criteria for the high anxiety subgroup. According to Kaplan-Meier probability estimates, patients with significant concurrent anxiety symptoms were more likely to respond by 12 weeks (66.4%) than those without significant anxiety symptoms (54.2%). There was no significant difference in response rates for sertraline vs. imipramine. Both drugs were effective at treating high baseline levels of anxiety, with 60% of sertraline patients and 58% of imipramine patients having 50% or greater reduction from baseline in HAM-D anxiety/somatization factor scores, and only 4.6% and 9.9%, respectively, reporting treatment-emergent worsening in anxiety at study endpoint. Despite the chronicity of depressive illness, acute treatment with both sertraline and imipramine significantly improved psychosocial and quality of life measures. High baseline levels of anxiety did not reduce overall antidepressant response but did somewhat delay the onset of response to sertraline or imipramine in patients with chronic depression.

  View details for Web of Science ID 000166954700003

  View details for PubMedID 11233456

• Pharmacotherapy of obsessive-compulsive disorder in a health maintenance organization 12th Annual Meeting of the European-College-of-Neuropsychopharmacology Koran, L. M., Leventhal, J. L., Fireman, B., Jacobson, A. AMER SOC HEALTH-SYSTEM PHARMACISTS. 2000: 1972–78

  Abstract

  The adequacy of pharmacotherapy for patients with obsessive-compulsive disorder (OCD) in a large, prepaid HMO was studied. An analysis was made of the computerized records for December 1, 1994, through April 30, 1998, for members of a Kaiser Permanente plan in northern California who were six years of age or older and had had continuous membership during an index year (May 1, 1995, to April 30, 1996) (1,728 million members). A total of 880 adults and 168 children and adolescents with chart-review-confirmed OCD and a pharmacy benefit were identified. The percentage of patients with an adequate drug trial, defined as > or = 56 days of continuous treatment with a serotonin-reuptake inhibitor or phenelzine at dosages at or above established minimal effective dosages, was determined. Forty-three percent of the adults and 28% of the children and adolescents who were newly diagnosed with OCD in the index year had an adequate trial of medication in the year after their first visit for OCD. By the second six months after the index year, only 75.2% of newly treated adults and 60.9% of newly treated children and adolescents continuing in the health plan filled at least one anti-OCD prescription. During the second follow-up year, these figures fell to 60.4% and 38.9%, respectively. Continuing-care patients filling a prescription in the index year were more likely than newly diagnosed patients to fill prescriptions in the two-year follow-up period, but their treatment still decreased substantially. Despite the typically chronic course of OCD, many patients with OCD who were enrolled in a large HMO appeared not to receive an adequate trial of pharmacotherapy or ongoing pharmacotherapy.

  View details for Web of Science ID 000165094300009

  View details for PubMedID 11094651

• Quality of life in obsessive-compulsive disorder PSYCHIATRIC CLINICS OF NORTH AMERICA Koran, L. M. 2000; 23 (3): 509-?

  Abstract

  Available data suggest that OCD has a substantial adverse effect on the HRQL of sufferers and their families. Although no consensus exists as to how to conceptualize or measure HRQL, studies using various concepts and measures will create a greater appreciation of the suffering and impairment entailed in this illness and a greater understanding of the costs, benefits, and limitations of treatment.

  View details for Web of Science ID 000089064100004

  View details for PubMedID 10986724

• Olanzapine augmentation for treatment-resistant obsessive-compulsive disorder JOURNAL OF CLINICAL PSYCHIATRY Koran, L. M., Ringold, A. L., Elliott, M. A. 2000; 61 (7): 514-517

  Abstract

  Adding the atypical neuroleptic risperidone to a serotonin reuptake inhibitor (SRI) has benefited patients with treatment-refractory obsessive-compulsive disorder (OCD). Since olanzapine and risperidone have similar serotonergic and dopaminergic receptor binding profiles, we tested the hypothesis that olanzapine augmentation would be beneficial in treatment-unresponsive OCD.For this 8-week trial, we recruited 10 adult OCD patients (DSM-IV criteria) unresponsive to fluoxetine (> or =60 mg/day) for > or =10 weeks, which was continued throughout the trial. Other psychotropic medications were discontinued. Subjects had OCD for > or =1 year, a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of > or =18, and no organic, psychotic, or other primary Axis I disorder. Two weeks after olanzapine, 2.5 mg/day, was added, and in the absence of responder status (Y-BOCS score decrease > or =25%) and limiting side effects, we increased the dose to 5 mg/day, and after 2 more weeks, to 10 mg/day for 4 weeks.The subjects had failed a mean of 3.3 SRI trials (range, 1-5) and had a mean +/- SD baseline Y-BOCS score of 29.0 +/- 4.9. Nine patients completed the trial. The subjects' mean +/- SD endpoint Y-BOCS score was 24.4 +/- 8.0 (a 16% decrease). The 3 responders' Y-BOCS scores dropped 68%, 30%, and 29%, but only 1 patient was rated "much improved." He maintained this improvement during a 6-month follow-up period taking olanzapine, 5 mg/day. Improvement in OCD was independent of improvement in mood symptoms. Six patients (60%) experienced significant weight gain.Olanzapine augmentation may benefit treatment-unresponsive OCD. Double-blind, placebo-controlled trials are warranted along with trials comparing risperidone and olanzapine augmentation.

  View details for Web of Science ID 000088589400009

  View details for PubMedID 10937610

• Issues and Strategies in Treating Refractory Obsessive-Compulsive Disorder CNS SPECTRUMS Koran, L. M., Saxena, S. 2000; 5 (6): 24-31

  View details for Web of Science ID 000207074600004

• Quality of Life in Obsessive-Compulsive Disorder CNS SPECTRUMS Stein, D. J., Allen, A., Bobes, J., Eisen, J. L., Figuera, M. L., Iikura, Y., Koran, L. M., Hollander, E. 2000; 5 (6): 37-39

  View details for Web of Science ID 000207074600006

• Lost human capital from early-onset chronic depression AMERICAN JOURNAL OF PSYCHIATRY Berndt, E. R., Koran, L. M., Finkelstein, S. N., Gelenberg, A. J., Kornstein, S. G., Miller, I. M., Thase, M. E., Trapp, G. A., Keller, M. B. 2000; 157 (6): 940-947

  Abstract

  Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings.The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender.Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all.Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

  View details for Web of Science ID 000087421300014

  View details for PubMedID 10831474

• A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. New England journal of medicine Keller, M. B., McCullough, J. P., Klein, D. N., Arnow, B., Dunner, D. L., Gelenberg, A. J., Markowitz, J. C., Nemeroff, C. B., Russell, J. M., Thase, M. E., Trivedi, M. H., Zajecka, J. 2000; 342 (20): 1462-1470

  Abstract

  Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain.We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments.Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and in the psychotherapy group, as compared with 73 percent in the combined-treatment group. (P<0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (P<0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug (e.g., headache, somnolence, dry mouth, nausea, and dizziness).Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.

  View details for PubMedID 10816183

• A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression NEW ENGLAND JOURNAL OF MEDICINE Keller, M. B., McCullough, J. P., Klein, D. N., Arnow, B., Dunner, D. L., Gelenberg, A. J., Markowitz, J. C., Nemeroff, C. B., Russell, J. M., Thase, M. E., Trivedi, M. H., Zajecka, J., Blalock, J. A., Borian, F. E., Jody, D. N., Debattista, C., Koran, L. M., Schatzberg, A. F., Fawcett, J., Hirschfeld, R. M., Keitner, G., Miller, I., Kocsis, J. H., Kornstein, S. G., Manber, R., Ninan, P. T., Rothbaum, B., Rush, A. J., Vivian, D., Rothbaum, B. 2000; 342 (20): 1462-1470

  Abstract

  Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain.We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments.Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and in the psychotherapy group, as compared with 73 percent in the combined-treatment group. (P<0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (P<0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug (e.g., headache, somnolence, dry mouth, nausea, and dizziness).Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.

  View details for Web of Science ID 000087068200001

• Hoarding in obsessive-compulsive disorder: A report of 20 cases JOURNAL OF CLINICAL PSYCHIATRY Winsberg, M. E., Cassic, K. S., Koran, L. M. 1999; 60 (9): 591-597

  Abstract

  We describe the demographic characteristics, hoarding phenomenology, comorbid disorders, family histories, and treatment response of 20 adult obsessive-compulsive disorder (OCD) patients exhibiting hoarding behavior.We utilized the Structured Clinical Interview for DSM-III-R, the Yale-Brown Obsessive Compulsive Scale, and a semistructured interview to gather data.We studied 9 women and 11 men. Their hoarding began from age 5 years to age 46 years (mean +/- SD age at onset = 20 +/- 11 years); hoarding was evident before the onset of other OCD symptoms in 9 patients. The most commonly hoarded items were newspapers and magazines, junk mail, old clothes, notes or lists, and old receipts. Hoarded material occupied from one room plus most or all closets to more than one room plus all closets, the garage, and yard. Seven patients rented additional storage space for hoarded items. Eighty-four percent of patients reported a family history of hoarding, and 80% grew up in a household where someone else hoarded. The most frequent primary motives for hoarding were fears of discarding something useful and discarding something that would be needed in the future. Lifetime prevalence of major depression and of impulse-control disorders, especially compulsive shopping, were high; only 3 patients met DSM-IV criteria for obsessive-compulsive personality disorder. Response of hoarding to selective serotonin reuptake inhibitors was less robust than is expected for obsessive-compulsive disorder.Whether hoarding behaviors mark a subset of obsessive-compulsive disorder patients with a different pathophysiology or functional anatomy deserves investigation.

  View details for Web of Science ID 000082856500005

  View details for PubMedID 10520977

• Citalopram and sexual side effects of selective serotonin reuptake inhibitors AMERICAN JOURNAL OF PSYCHIATRY Pallanti, S., Koran, L. M. 1999; 156 (5): 796-796

  View details for Web of Science ID 000080095400036

  View details for PubMedID 10327919

• Citalopram for treatment-resistant obsessive-compulsive disorder EUROPEAN PSYCHIATRY Pallanti, S., Quercioli, L., Paiva, R. S., Koran, L. M. 1999; 14 (2): 101-106

  Abstract

  We investigated the comparative efficacy of citalopram vs. citalopram administered with clomipramine, in treatment-resistant obsessive-compulsive disorder (OCD). Sixteen adult outpatients participated in a 90-day, randomized, open-label trial. Eligible patients were aged 18 to 45 years, had moderate to severe DSM-III-R OCD of >/= one year's duration, a baseline Yale-Brown scale (Y-BOCS) score of >/= 25 and no other active axis I diagnosis, and had failed adequate clomipramine and fluoxetine trials. The citalopram-plus-clomipramine group (n = 9) experienced a significantly larger percent decrease in mean Y-BOCS score by day 90 than the citalopram alone group (n = 7). Only one citalopram patient decreased her score by >/= 35%, and two by >/= 25%. All nine citalopram-plus-clomipramine patients experienced decreases of 35%. Side effects were mild to moderate in both groups. We also treated with citalopram six OCD patients who had not tolerated fluoxetine alone and clomipramine alone; three achieved Y-BOCS score decreases of >/= 35% at 90 days. Since citalopram does not significantly affect clomipramine metabolism, the improvement in the combined drug group is unlikely to have resulted from increased plasma clomipramine levels. Double-blind controlled trials are needed of citalopram in OCD, and of combining citalopram with clomipramine in treatment-resistant OCD.

  View details for Web of Science ID 000080508000007

  View details for PubMedID 10572334

• Obsessive-Compulsive And Related Disorders in Adults: A Comprehensive Clinical Guide Koran, L. M. Cambridge University Press. 1999
• Predictors of response to acute treatment of chronic and double depression with sertraline or imipramine JOURNAL OF CLINICAL PSYCHIATRY Hirschfeld, R. M., Russell, J. M., Delgado, P. L., Fawcett, J., Friedman, R. A., Harrison, W. M., Koran, L. M., Miller, I. W., Thase, M. E., Howland, R. H., Connolly, M. A., Miceli, R. J. 1998; 59 (12): 669-675

  Abstract

  The literature on predictors of response to treatment of nonchronic major depression has identified shorter duration of illness, acute onset, and less severity of illness as positive predictors. Unfortunately, there are almost no data on predictors of response to treatment for chronic depression. This study examined predictors of response to pharmacotherapy (sertraline or imipramine) in the treatment of outpatients who had DSM-III-R-defined chronic major or double depression.The acute phase of the Chronic Major Depression and Double Depression Study is a double-blind, randomized, parallel-group 12-week comparison of sertraline and imipramine. Analyses are based on 623 patients who comprised the intent-to-treat sample, of whom 299 were nonresponders and 324 were responders, defined by a priori criteria as either remission or satisfactory therapeutic response. A stepwise logistic multiple regression analysis was performed on candidate clinical, psychosocial, and demographic variables previously identified as statistically significant in an attempt to develop a predictive model of positive antidepressant response.The sociodemographic variables that were predictive of positive response included living with spouse or partner or being at least a high school graduate. With regard to symptomatology and clinical history, responders had significantly lower baseline depression severity scores. In general, comorbid anxiety, substance abuse, and personality disorders did not influence rates of response. However, the presence of depressive personality traits was associated with a higher nonresponse rate. Among psychosocial variables, longer duration of personal relationships as well as higher baseline quality of life were associated with positive response. A stepwise logistic multiple regression identified 5 variables-living with spouse or partner, higher educational level, passive-aggressive personality, lower introverted-tense personality traits, and higher quality of life--that significantly and independently contributed to the predictive model. This model correctly classified 67% of patients.A higher baseline quality of life, living with spouse or partner, and having more education were the strongest predictors of response to acute pharmacotherapy among chronically depressed patients. Clinical variables and comorbidity were not identified as independent predictors, although personality traits did appear to influence treatment response. Overall, the predictive value of these baseline measures was modest, and therefore of limited clinical utility.

  View details for Web of Science ID 000078116900005

  View details for PubMedID 9921701

• Maintenance phase efficacy of sertraline for chronic depression - A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Keller, M. B., Kocsis, J. H., Thase, M. E., Gelenberg, A. J., Rush, A. J., Koran, L., Schatzberg, A., Russell, J., Hirschfeld, R., Klein, D., McCullough, J. P., Fawcett, J. A., Kornstein, S., LaVange, L., Harrison, W. 1998; 280 (19): 1665-1672

  Abstract

  The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness.To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression").A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996.Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers.Maintenance treatment with either sertraline hydrochloride (n = 77) in flexible doses up to 200 mg or placebo (n = 84).A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase.Time to recurrence of major depression.Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P = .002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P = .001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P = .005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata.Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.

  View details for Web of Science ID 000076980700031

  View details for PubMedID 9831997

• The treatment of chronic depression, part 2: A double-blind, randomized trial of sertraline and imipramine JOURNAL OF CLINICAL PSYCHIATRY Keller, M. B., Gelenberg, A. J., Hirschfeld, R. M., Rush, A. J., Thase, M. E., Kocsis, J. H., Markowitz, J. C., Fawcett, J. A., Koran, L. M., Klein, D. N., Russell, J. M., Kornstein, S. G., McCullough, J. P., Davis, S. M., Harrison, W. M. 1998; 59 (11): 598-607

  Abstract

  Chronic depression appears to be a common, frequently disabling illness that is often inadequately treated. Unlike episodic depressions with shorter illness duration, neither acute nor long-term treatment approaches for chronic depression have been well studied.635 outpatients at 12 sites who met DSM-III-R criteria for chronic major depression or double depression were randomly assigned to 12 weeks of double-blind treatment with either sertraline (in daily doses of 50-200 mg) or imipramine (in daily doses of 50-300 mg). Efficacy and safety were assessed either weekly or every 2 weeks during the 12 weeks of acute treatment.Despite high rates of chronicity (mean duration of major depression = 8.9+/-9.1 years; mean duration of dysthymia = 23+/-13 years) and high rates of comorbidity, 52% of patients achieved a satisfactory therapeutic response to sertraline or imipramine (by a conservative, intent-to-treat analysis). Approximately 21% of the patients who had achieved a therapeutic response at week 12 had not done so at week 8, confirming the longer time to response in depressions with high chronicity. Patients treated with sertraline reported significantly fewer adverse events and were significantly less likely to discontinue treatment due to side effects than imipramine-treated patients (6.3% vs. 12.0%).These results indicate that patients suffering from depression with high chronicity can achieve a good therapeutic response to acute treatment with either sertraline or imipramine, although sertraline is better tolerated.

  View details for Web of Science ID 000077383000007

  View details for PubMedID 9862606

• The treatment of chronic depression, part 1: Study design and rationale for evaluating the comparative efficacy of sertraline and imipramine as acute, crossover, continuation, and maintenance phase therapies JOURNAL OF CLINICAL PSYCHIATRY Rush, A. J., Koran, L. M., Keller, M. B., Markowitz, J. C., Harrison, W. M., Miceli, R. J., Fawcett, J. A., Gelenberg, A. J., Hirschfeld, R. M., Klein, D. N., Kocsis, J. H., McCullough, J. P., Schatzberg, A. F., Thase, M. E. 1998; 59 (11): 589-597

  Abstract

  Chronic depressions are common, disabling, and undertreated, and prior chronicity predicts future chronicity. However, few studies directly inform the acute or maintenance phase treatments of chronic depressions and even less is known about the effects of treatment on psychosocial functioning.We describe the design and rationale for 2 parallel double-blind, randomized, multicenter acute and maintenance phase treatment trials. One focused on DSM-III-R major depression currently in a chronic (> or = 2 years) major depressive episode, the other on DSM-III-R major depression with concurrent DSM-III-R dysthymia ("double depression").Considering the critical knowledge deficits, we designed a 12-week acute phase safety and efficacy trial of sertraline versus imipramine, followed by a 16-week continuation treatment phase for subjects with a satisfactory therapeutic response. Patients receiving sertraline who successfully completed the continuation phase entered a 76-week maintenance trial to compare sertraline with placebo; those taking imipramine continued without a placebo substitution. As part of the acute trial, subjects completing but failing to respond to the initial 12-week acute phase medication were crossed over (double-blind) to the alternative medication for a 12-week acute phase trial. We obtained naturalistic follow-up data (up to 18 months) for subjects exiting the protocol at any time.Multiphase protocols for chronic depression can test efficacy by randomized contrasts as well as shed light on key clinical issues such as the degree of response or attrition expected at particular times in a trial or the preferred medication sequence in a potential multistep treatment program.

  View details for Web of Science ID 000077383000006

  View details for PubMedID 9862605

• Intravenous clomipramine challenge in obsessive-compulsive disorder: Predicting response to oral therapy at eight weeks BIOLOGICAL PSYCHIATRY Sallee, F. R., Koran, L. M., Pallanti, S., Carson, S. W., Sethuraman, G. 1998; 44 (3): 220-227

  Abstract

  Challenge with intravenous clomipramine (CMI) is serotonin selective and has been reported to transiently exacerbate symptoms in obsessive-compulsive disorder (OCD) patients, and to predict subsequent response to oral CMI therapy.We administered CMI (12.5 mg, i.v.) to medication free OCD patients (N = 29) and normal controls (N = 22) to characterize neurohormonal response. A subset of OCD patients (26/29), was then treated with either pulse load i.v. or oral CMI followed by 8 weeks of oral CMI therapy.In response to CMI challenge, OCD patients exhibit blunted cortisol and exaggerated growth hormone response relative to normal controls. OCD patients differ from controls in "sadness" ratings, with control exhibiting increased dysphoria in response to CMI. Growth hormone response to CMI challenge predicts treatment response (> or = 25% decreases YBOCS from baseline) to oral CMI at 8 weeks.Growth hormone abnormalities associated with OCD in response to CMI challenge differentiates nonresponders after 8 weeks of oral CMI treatment from responders.

  View details for Web of Science ID 000075012900009

  View details for PubMedID 9693393

• Pulse loading versus gradual dosing of intravenous clomipramine in obsessive-compulsive disorder EUROPEAN NEUROPSYCHOPHARMACOLOGY Koran, L. M., Pallanti, S., Paiva, R. S., Quercioli, L. 1998; 8 (2): 121-126

  Abstract

  We compared gradually increased to pulse loaded doses of open-label, intravenous clomipramine (CMI) in patients with obsessive-compulsive disorder (OCD).We treated adult outpatients with DSM-III-R OCD, who had no prior exposure to effective treatments. Pulse loading patients received 150 mg on day 1; 150 mg or 200 mg on day 2. Gradual dosing patients received 25 mg per day increased to 200 mg per day over 2 weeks and then continued for a mean of 43 days (n=40). After i.v. dosing, all patients received oral CMI; the total treatment period was 6 months.Pulse loading completers (n=7) had a rapid, dramatic response (mean Y-BOCS score decrease of 32% five days after pulse-loading). At this point (day 7), completers in the gradual intravenous group (n=20) exhibited no mean change in Y-BOCS score. The pulse loading group reached both a 25% or greater and a 50% or greater decrease in Y-BOCS score statistically and clinically significantly faster than the gradual group.Pulse-loaded intravenous CMI for the treatment of OCD deserves further study.

  View details for Web of Science ID 000073550400006

  View details for PubMedID 9619690

• A 2-year study of sertraline in the treatment of obsessive-compulsive disorder INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY Rasmussen, S., Hackett, E., DuBoff, E., Greist, J., Halaris, A., Koran, L. M., Liebowitz, M., Lydiard, R. B., McElroy, S., Mendels, J., O'Connor, K. 1997; 12 (6): 309-316

  Abstract

  The present study investigated the tolerability, safety profile, and anti-obsessional efficacy of sertraline, a selective serotonin reuptake inhibitor, during long-term treatment of patients with obsessive-compulsive disorder (OCD). Fifty-nine OCD patients who had completed a 1 year double-blind, fixed dose study comparing sertraline and placebo subsequently entered a 1-year open extension. Among the 51 patients who had been treated with sertraline during the double-blind phase, the mean total duration of sertraline treatment was 690 days. Only treatment responders who completed the 52-week double-blind treatment phase were permitted to enter the open extension. The higher rate (p < 0.02) of sertraline patients (51 out of 241) than of placebo patients (eight out of 84), who responded to treatment and entered the open-label phase is therefore consistent with the greater mean improvement observed in the sertraline group during double-blind treatment. Placebo responders differed from sertraline responders in that they were less impaired at baseline of the double-blind study [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18.5 versus 23.4] and they exhibited less improvement during double-blind treatment (-6.1 versus -11.4). In the open-label phase all patients received sertraline at a starting dose of 50 mg once a day, titrated in 50 mg increments to a maximum dose of 200 mg according to clinical response. At end-point the mean Y-BOCS score for all patients decreased by a further 3.6 points. Patients previously treated with placebo showed greater improvement after being switched to sertraline than those who received continued sertraline treatment. Patients who completed the study and received 2 full years of sertraline treatment (n = 38) exhibited a mean improvement of 15.6 points using the Y-BOCS. Sertraline was well tolerated during both the double-blind phase and the open extension, and the incidence of adverse experiences was generally reduced during the second year of treatment. Three patients discontinued open treatment because of adverse experiences. Long-term sertraline treatment did not appear to be associated with the emergence, increased incidence, or increased severity of adverse experiences or clinically significant abnormalities in laboratory tests, vital signs, or the electrocardiogram. The study supports the long-term safety and tolerability of sertraline over a 2-year treatment course and the sustained efficacy of sertraline in patients with OCD.

  View details for Web of Science ID 000071359000003

  View details for PubMedID 9547132

• Microbial removal of alkanes from dilute gaseous waste streams: Kinetics and mass transfer considerations BIOTECHNOLOGY PROGRESS Barton, J. W., Klasson, K. T., Koran, L. J., Davison, B. H. 1997; 13 (6): 814-821

  Abstract

  Treatment of dilute gaseous hydrocarbon waste streams remains a current need for many industries, particularly as increasingly stringent environmental regulations and oversight force emission reduction. Biofiltration systems hold promise for providing low-cost alternatives to more traditional, energy-intensive treatment methods such as incineration and adsorption. Elucidation of engineering principles governing the behavior of such systems, including mass transfer limitations, will broaden their applicability. Our processes exploit a microbial consortium to treat a mixture of 0.5% n-pentane and 0.5% isobutane in air. Since hydrocarbon gases are sparingly soluble in water, good mixing and high surface area between the gas and liquid phases are essential for biodegradation to be effective. One liquid-continuous columnar bioreactor was operated for more than 30 months with continued degradation of n-pentane and isobutane as sole carbon and energy sources. The maximum degradation rate observed in this gas-recycle system was 2 g of volatile organic compounds (VOC)/(m3.h). A trickle-bed bioreactor was operated continuously for over 24 months to provide a higher surface area (using a structured packing) with increased rates. Degradation rates consistently achieved were approximately 50 g of VOC/(m3.h) via single pass in this gas-continuous columnar system. Effective mass transfer coefficients comparable to literature values were also measured for this reactor; these values were substantially higher than those found in the gas-recycle reactor. Control of biomass levels was implemented by limiting the level of available nitrogen in the recirculating aqueous media, enabling long-term stability of reactor performance.

  View details for Web of Science ID A1997YK69700019

  View details for PubMedID 9413140

• Obsessive-compulsive disorder in pregnancy, the puerperium, and the premenstruum JOURNAL OF CLINICAL PSYCHIATRY Williams, K. E., Koran, L. M. 1997; 58 (7): 330-334

  Abstract

  Recent reports suggest that pregnancy and the puerperium may precipitate or exacerbate obsessive-compulsive disorder (OCD). The influence of this illness on other reproductive events, such as the premenstruum, is unknown. We examined retrospectively the relationships of pregnancy, the puerperium, and premenstruum to the course of OCD in 57 women.Women outpatients with OCD meeting DSM-III-R criteria completed a standardized telephone interview administered by a psychiatric resident. They were asked retrospectively about the clinical course of their illness premenstrually and during and after pregnancy.Of 72 women eligible for the study, 79% (N = 57) completed the interview. Premenstrual worsening of OCD was described by 24 (42%) of the 57 women, and 12 (21%) described premenstrual dysphoria. Of the 57 women, 38 (67%) had been pregnant at least once; 31 (54%) had delivered at least one child. Pregnancy was associated with the onset of OCD in only 5 (13%) of the 38 women. Of the 29 women with preexisting OCD who became pregnant, 20 (69%) described no change in symptoms during pregnancy, 5 (17%) described worsening, and 4 (14%) described improvement. Postpartum exacerbation of OCD symptoms was reported by 7 (29%) of the 24 women with preexisting OCD who completed full-term pregnancies. Nine (37%) of the 24 women with both preexisting OCD and completed pregnancies also reported postpartum depression.The premenstrual and postpartum exacerbation of OCD symptoms in some women suggests that the course of this disorder may, in some cases, be influenced by changes in gonadal hormones. Our finding that women with OCD may be at increased risk for postpartum depression underscores the importance of careful postpartum evaluation of women with OCD to prevent maternal and infant morbidity.

  View details for Web of Science ID A1997XQ03400016

  View details for PubMedID 9269260

• Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial 147th Annual Meeting of the American-Psychiatric-Association SCHNEIDER, L. S., Small, G. W., Hamilton, S. H., Bystritsky, A., Nemeroff, C. B., Meyers, B. S., Abuzzahab, F. S., Alexopoulos, G. S., Bielski, R. J., BORISON, R. L., BROD, M. S., COHENCOLE, S. A., Cohn, C. K., DOWNS, J. M., DuPont, R. L., Ferguson, J. M., Folks, D. G., GOTTLIEB, G. L., Graber, B., MENOLASCINO, F. J., Halaris, A. E., Hartford, J. T., Hertzman, M., JEFFERSON, J. W., Jeste, D. V., Koran, L. M., LAZARUS, L. W., NAKRA, B. R., Oxenkrug, G. F., Rappaport, S. A., Rosenthal, M. H., Salzman, C., Shrivastava, R., STOKES, P. E., Winston, J. L., Wheadon, D. W., SCHATZ, E. J., MARVEL, D. E., ALBRITTON, R., Tollefson, G. D. LIPPINCOTT WILLIAMS & WILKINS. 1997: 97–106

  View details for Web of Science ID A1997WR47100002

• Rapid benefit of intravenous pulse loading of clomipramine in obsessive-compulsive disorder AMERICAN JOURNAL OF PSYCHIATRY Koran, L. M., Sallee, F. R., Pallanti, S. 1997; 154 (3): 396-401

  Abstract

  The authors conducted a randomized, double-blind, placebo-controlled trial of intravenous versus oral pulse loading of clomipramine in patients with obsessive-compulsive disorder to test two hypotheses: 1) intravenous pulse loading will cause greater immediate improvement than oral pulse loading and 2) patients who respond to pulse loading will continue to improve during 8 weeks of oral clomipramine treatment.Fifteen patients with DSM-III-R obsessive-compulsive disorder of at least 1 year's duration and baseline Yale-Brown Obsessive Compulsive Scale scores of 17 or higher were enrolled in the study. Yale-Brown scale ratings were made 4.5 days after double-blind oral or intravenous pulse loading of clomipramine, and patients were then given 150 mg/day of oral clomipramine with increases of 25 mg every 4 days to 250 mg/day as tolerated or, in two cases, other selective serotonin reuptake inhibitors (SSRIs).The first hypothesis was confirmed: 4.5 days after the second pulse-loaded dose, six of seven patients given intravenous clomipramine but only one of eight given oral medication responded to the drug. After 8 weeks of oral clomipramine, the results partially supported the second hypothesis: four of six patients who had responded to intravenous clomipramine continued their improvement, but those who had responded to pulse loading did not improve statistically significantly more than those who had not.Intravenous pulse loading of clomipramine may be a valuable new treatment for obsessive-compulsive disorder, particularly for patients who have failed oral treatment trials.

  View details for Web of Science ID A1997WK84200015

  View details for PubMedID 9054789

• The undertreatment of dysthymia JOURNAL OF CLINICAL PSYCHIATRY Shelton, R. C., Davidson, J., Yonkers, K. A., Koran, L., Thase, M. E., Pearlstein, T., Halbreich, U. 1997; 58 (2): 59-65

  Abstract

  Dysthymia is a chronic depressive condition that is quite prevalent. This condition can exact a significant toll on the general health and quality of life in the affected individual. Despite the frequency and consequences of dysthymia, however, the condition is often not diagnosed or treated. We present data on prior treatment from 410 patients with DSM-III-R dysthymia, primary type, early onset without concurrent major depression.Axis I and II diagnoses were made by using the Structured Clinical Interviews for DSM-III-R, Patient Version (SCID-P) and SCID II for Personality Disorders. The Hamilton Rating Scale for Depression and the Clinical Global Impressions scale were also completed. Prior treatment was assessed, with special attention paid to previous antidepressant drug therapy and psychotherapy.Although the mean duration of dysthymia was about 30 years and almost half of the patients had previous episodes of major depression, only 41.3% had been treated with antidepressants and 56.1% with psychotherapy. A past history of major depression increased the frequency of prior antidepressant pharmacotherapy (45.7%) and psychotherapy (59.4%) compared with no history of major depression (36.8% and 40.9%, respectively). Comorbid personality disorder increased the likelihood of prior psychotherapy (70.7% vs. 49.6%) while having no effect on past pharmacotherapy. A history of substance abuse did not affect the history of antidepressant or psychotherapy treatment. In this study, dysthymia and psychosocial outcomes improved with sertraline and imipramine treatment.Dysthymic patients in this sample were significantly undertreated. Newer antidepressant agents may alter the potential for pharmacotherapy interventions in this vulnerable population.

  View details for Web of Science ID A1997WM26100002

  View details for PubMedID 9062374

• Fluoxetine serum levels are unrelated to outcome in obsessive-compulsive disorder. Am J Psychiatry Koran LM, Cain JW, Dominguez RA, Rush AJ, Thiemann S 1997: 396-401
• Are fluoxetine plasma levels related to outcome in obsessive-compulsive disorder? AMERICAN JOURNAL OF PSYCHIATRY Koran, L. M., Cain, J. W., Dominguez, R. A., Rush, A. J., Thiemann, S. 1996; 153 (11): 1450-1454

  Abstract

  In obsessive-compulsive disorder, the relationship between blood levels of serotonin reuptake inhibitors and clinical outcome is unclear. In a multicenter trial, the authors examined the relationship between steady state plasma levels of fluoxetine and norfluoxetine (determined after 7 weeks of treatment), and their sum, and clinical outcome.Ratings of symptom severity of obsessive-compulsive disorder (Yale-Brown Obsessive Compulsive Scale scores) were obtained at baseline and after 13 weeks for 200 adult outpatients with moderately severe obsessive-compulsive disorder treated with fluoxetine doses of 20 mg/day (N = 68), 40 mg/day (N = 64), and 60 mg/day (N = 68).Mean plasma levels of fluoxetine and norfluoxetine were statistically significantly higher with higher dose. Statistical analyses revealed no significant relationship for plasma level of either molecule or their sum in predicting endpoint percent change in obsessive-compulsive scores. Plasma levels of patients with a marked response (decrease of 50% or more in obsessive-compulsive score) did not differ significantly from those of nonresponders (less than a 25% decrease in obsessive-compulsive score). No hint was seen of a therapeutic window or of a relationship limited to one gender or within the lowest dose group (20 mg/day). However, since S-norfluoxetine is a much more potent serotonin reuptake inhibitor than R-norfluoxetine, the absence of chiral (stereospecific) assays in this study limits the results.Steady state plasma levels of fluoxetine and norfluoxetine are not related to clinical outcome in patients with obsessive-compulsive disorder. Individual patients can be told only that the optimum dose of fluoxetine for them will be the dose that produces the largest therapeutic effect with the smallest side effect burden. Future studies should examine the predictive utility of measures of serotonergic neuronal function and, if plasma levels of norfluoxetine are examined, the use of chiral assays.

  View details for Web of Science ID A1996VP75400012

  View details for PubMedID 8890679

• Impact of physical illness on quality of life and antidepressant response in geriatric major depression. Fluoxetine Collaborative Study Group. Journal of the American Geriatrics Society Small, G. W., Birkett, M., Meyers, B. S., Koran, L. M., Bystritsky, A., Nemeroff, C. B. 1996; 44 (10): 1220-1225

  Abstract

  Because physical illness may influence quality of life, we assessed its impact on functional status and treatment outcome in older depressed patients who participated in a clinical trial, which showed a significantly higher remission rate for fluoxetine over placebo (31.6% vs 18.6%, P < .001).Six-week, randomized, double-blind, placebo-controlled trial of fluoxetine, 20 mg daily.Multiple clinical sites, both university and private.Outpatients (N = 671) were > or = 60 years (mean +/- SD = 67.7 +/- 5.7), met DSM-III-R criteria for unipolar major depression and had baseline scores > or = 16 on the Hamilton Depression Rating Scale.The 36-item short-form health survey (SF-36) was used to measure baseline and posttreatment functional health and well-being. Physical illness was rated by number of current chronic or historical illnesses. Change from baseline to endpoint in the Hamilton Depression Rating Scale total score was used to measure depression outcome.Most patients reported physical illness: 83% had one or more chronic illness, and 89% had one or more historical illness. Greater numbers of baseline chronic illness indicated worse physical functioning, general health perceptions, and vitality and greater bodily pain and role limitation from physical problems. Historical physical illness was associated with worse physical functioning, vitality, general health perceptions, social functioning, and mental health. Although the number of chronic illnesses did not influence treatment response, historical physical illness was associated with greater fluoxetine response and lower placebo response.These findings suggest that both current and previous physical illness are associated with lower quality of life in geriatric depression and that depressed older patients with chronic physical illness respond to antidepressants as well as those without such illness. Recovery from previous physical illness should be explored as a potential predictor of antidepressant treatment outcome.

  View details for PubMedID 8856002

• Impact of physical illness on quality of life and antidepressant response in geriatric major depression 7th International-Psychogeriatric-Association Congress Small, G. W., Birkett, M., Meyers, B. S., Koran, L. M., Bystritsky, A., Nemeroff, C. B., Abuzzahab, F. S., Alexopoulos, G. S., Bielski, R. J., BORISON, R. L., BROD, M. S., COHENCOLE, S. A., Cohn, C. K., DOWNS, J. M., DuPont, R. L., Ferguson, J. M., Folks, D. G., GOTTLIEB, G. L., Graber, B., MENOLASCINO, F. J., Halaris, A. E., Hartford, J. T., Hertzman, M., JEFFERSON, J. W., Jeste, D. V., LAZARUS, L. W., Nakra, B. R., Oxenkrug, G. F., Rappaport, S. A., Rosenthal, M. H., Salzman, C., Shrivastava, R. K., STOKES, P. E., Winston, J. L., Wheadon, D. W., SCHATZ, E. J., MARVEL, D. E., ALBRITTON, R., Tollefson, G. D., Lilly, E. WILLIAMS & WILKINS. 1996: 1220–25

  View details for Web of Science ID A1996VM27700012

• A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia ARCHIVES OF GENERAL PSYCHIATRY Thase, M. E., Fava, M., Halbreich, U., Kocsis, J. H., Koran, L., Davidson, J., Rosenbaum, J., Harrison, W. 1996; 53 (9): 777-784

  Abstract

  Despite the high prevalence of dysthymia and its associated morbidity, few controlled trials have evaluated the efficacy of antidepressant medication for this disorder. A 12-week, double-blind, placebo-controlled, randomized, multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia.A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major depression were randomized to 12 weeks of treatment with sertraline, imipramine, or placebo.Both active treatments resulted in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01 for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins Symptom Checklist (P < .05), and the self-rated version of the Inventory of Depressive Symptoms (P < .05). With the use of a Clinical Global impressions improvement score of 1 or 2 (very much or much improved) to define response, response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo (P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events (P = .001 and P < .001, respectively).Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication.

  View details for Web of Science ID A1996VG33300003

  View details for PubMedID 8792754

• Will pindolol augment the response to a serotonin reuptake inhibitor in obsessive-compulsive disorder? JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Koran, L. M., Mueller, K., Maloney, A. 1996; 16 (3): 253-254

  View details for Web of Science ID A1996UR18400011

  View details for PubMedID 8784659

• Quality of life for patients with obsessive-compulsive disorder AMERICAN JOURNAL OF PSYCHIATRY Koran, L. M., Thienemann, M. L., Davenport, R. 1996; 153 (6): 783-788

  Abstract

  The health-related quality of life of patients with obsessive-compulsive disorder was compared to published norms for the general U.S. population and for patients with either depressive disorders or diabetes.Sixty medication-free outpatients with moderate to severe obsessive-compulsive disorder were evaluated by using the Structured Clinical Interview for DSM-III-R and the Yale-Brown Obsessive Compulsive Scale. Health-related quality of life was measured with the self-rated Medical Outcomes Study 36-Item Short-Form Health Survey.The instrumental role performance and social functioning of the patients with obsessive-compulsive disorder were worse than those of the general population and of diabetes patients. The more severe the obsessive-compulsive disorder, the lower were the patients' social functioning scores, even after depression ratings were controlled for; scores on instrumental role performance did not correlate with severity of obsessive-compulsive disorder. The ratings of the obsessive-compulsive disorder patients on physical health domains resembled those of the general population and exceeded those of the diabetes patients. The general health and physical health ratings of the obsessive-compulsive disorder patients exceeded those of the depressed patients. In mental health domains, after adjustment for differences in gender distribution, quality of life ratings were similar for the patients with obsessive-compulsive disorder and those with depressive disorders.Moderate to severe obsessive-compulsive disorder is associated with impaired social functioning and impaired instrumental role performance, but only impairment in social functioning is linearly related to severity of obsessive-compulsive disorder.

  View details for Web of Science ID A1996UN63200008

  View details for PubMedID 8633690

• Fluvoxamine versus clomipramine for obsessive-compulsive disorder: A double-blind comparison JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Koran, L. M., McElroy, S. L., Davidson, J. R., Rasmussen, S. A., Hollander, E., Jenike, M. A. 1996; 16 (2): 121-129

  Abstract

  The efficacy and tolerability of fluvoxamine (100-300 mg/day) and clomipramine (100-250 mg/day) were compared in a randomized, double-blind, parallel-group study of 79 patients with obsessive-compulsive disorder (OCD) without coexisting major depression. After a 2-week placebo lead-in period, patients were randomized to fluvoxamine (37 patients) or clomipramine (42 patients) for 10 weeks. Efficacy was evaluated with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the National Institute of Mental Health Obsessive-Compulsive scale, and Patient and Clinical Global Improvement scales. Hamilton Rating Scale for Depression scores and somatic symptoms were also assessed. Seventy-eight percent of fluvoxamine patients and 64% of clomipramine patients completed the study. At the end of treatment, 56% of fluvoxamine patients were classified as responders (> or = 25% decrease in Y-BOCS score), compared with 54% of clomipramine patients. Both groups showed steady improvement throughout the study; no statistically significant differences were observed between the groups for any efficacy variable at any time. A similar percentage of patients in both groups withdrew because of adverse events. No serious adverse events related to drug occurred with either drug. Insomnia, nervousness, and dyspepsia were more statistically frequent with fluvoxamine; dry mouth and postural hypotension were more frequent with clomipramine. In this study, fluvoxamine and clomipramine were equally effective in reducing OCD symptoms over a 10-week treatment period but displayed different side effect profiles.

  View details for Web of Science ID A1996UD63200004

  View details for PubMedID 8690827

• Electroconvulsive therapy PSYCHIATRIC SERVICES Koran, L. M. 1996; 47 (1): 23-23

  View details for Web of Science ID A1996TN38700003

  View details for PubMedID 8925339

• PREDICTING RESPONSE TO FLUOXETINE IN GERIATRIC-PATIENTS WITH MAJOR DEPRESSION JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Koran, L. M., Hamilton, S. H., Hertzman, M., Meyers, B. S., Halaris, A. E., Tollefson, G. D., DOWNS, J. M., Folks, D. G., Jeste, D. V., LAZARUS, L. W., Satlin, A. 1995; 15 (6): 421-427

  Abstract

  No consensus exists regarding whether early response to an antidepressant strongly predicts a good outcome, what is the criterion for early response, or when to measure it. We hypothesized that early response (> or = 20% decrease in HAM-d21) after any of weeks 1, 2, or 3 of fluoxetine treatment of major depression in geriatric outpatients would predict a favorable outcome by week 6 or an earlier endpoint accurately enough for clinical use. We also hypothesized that the week 1, 2, and 3 percent changes in 21-item Hamilton Rating Scale for Depression (HAM-D21) would predict the percent change at week 6 (or endpoint) accurately enough for clinical use. We enrolled 671 elderly outpatients with unipolar DSM-III-R major depression in a double-blind, placebo-controlled trial of fluoxetine, 20 mg/day. For analysis, fluoxetine-treated patients were randomly divided into a development set (N = 154) for a preliminary test of our criteria and a validation set (N = 181) to validate the development data set's results. Early responders at weeks 1, 2, and 3 were statistically significantly more likely to experience marked improvement or remission than those lacking early response. However, at week 3, this criterion correctly classified only about three-fourths of patients with regard to marked improvement and only about two-thirds with regard to remission. Moreover, about one-third of patients predicted to experience marked improvement and about three-fifths of those predicted to remit did not. The continuous variable, percent change in HAM-D21, did not produce predictive results of any greater clinical utility. We believe that the sensitivity, specificity, false-positive rate, false-negative rate, and kappa of outcome predictions all should be reported in future studies. Without a full set of descriptive statistics, clinicians can be misled by statistically significant results.

  View details for Web of Science ID A1995TK56700008

  View details for PubMedID 8748431

• COMPARING THE COST-EFFECTIVENESS OF PSYCHIATRIC TREATMENTS - BULIMIA-NERVOSA PSYCHIATRY RESEARCH Koran, L. M., Agras, W. S., ROSSITER, E. M., Arnow, B., Schneider, J. A., Telch, C. F., Raeburn, S., Bruce, B., Perl, M., Kraemer, H. C. 1995; 58 (1): 13-21

  Abstract

  We conducted an exploratory post hoc study that compared the cost effectiveness of five treatments for bulimia nervosa: 15 weeks of cognitive behavioral therapy (CB) followed by three monthly sessions, 16 weeks (Med16) and 24 weeks (Med24) of desipramine (< or = 300 mg/day), and CB combined with desipramine for those durations (Combo16 and Combo24). We illustrate how a treatment's cost effectiveness varies according to when evaluation is done and how effectiveness and cost are defined. At 32 weeks, Med16 appears the most cost-effective treatment, and Combo16 appears the least. At 1 year, Med24 appears the most cost-effective treatment, and Combo16 appears the least. Using this post hoc analysis as an example, we discuss the pitfalls and limitations of cost-effectiveness analysis of psychiatric treatments.

  View details for Web of Science ID A1995RW58200002

  View details for PubMedID 8539308

• PSYCHIATRISTS PATIENTS PSYCHIATRIC SERVICES Koran, L. M. 1995; 46 (9): 873-873

  View details for Web of Science ID A1995RR89900002

  View details for PubMedID 7583493

• A 1-YEAR DOUBLE-BLIND PLACEBO-CONTROLLED FIXED-DOSE STUDY OF SERTRALINE IN THE TREATMENT OF OBSESSIVE-COMPULSIVE DISORDER INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY Greist, J. H., JEFFERSON, J. W., Kobak, K. A., Chouinard, G., DuBoff, E., Halaris, A., Kim, S. W., Koran, L., LIEBOWTIZ, M. R., Lydiard, B., McElroy, S., Mendels, J., Rasmussen, S., White, K., FLICKER, C. 1995; 10 (2): 57-65

  Abstract

  The objective of this study was to evaluate the safety and efficacy, over a 1 year treatment period, of three dose levels of sertraline and placebo in the treatment of non-depressed adult out-patients with obsessive-compulsive disorder (OCD). Following 1 week of single-blind placebo washout, patients (n = 325) from 11 sites following identical protocols were randomly assigned to 12 weeks of double-blind treatment with one of three fixed doses of sertraline (50, 100 or 200 mg) or placebo. At the end of 12 weeks, treatment responders (including placebo patients) were offered an additional 40 weeks of double-blind treatment at their assigned doses. Efficacy measures were the Yale-Brown Obsessive Compulsive Scale, the NIMH Global Obsessive Compulsive Scale, Clinical Global Impressions of Severity of Illness and Global Improvement and the Maudsley Obsessive Compulsive Inventory. Patients in the pooled sertraline group showed greater improvement than placebo-treated patients on all efficacy measures, based on the endpoint analyses. Moreover, pairwise comparisons at endpoint revealed a significant effect on all three investigator-rated scales in patients receiving 50 or 200 mg of sertraline; in the 100 mg group, there was a significant effect on the NIMH Global Obsessive Compulsive Scale only. Patients completing 3 months of sertraline treatment exhibited excellent toleration and sustained improvement during an additional 40 weeks of therapy. Results support the safety, efficacy and tolerability of daily doses of 50-200 mg of sertraline in the long-term treatment of patients with OCD.

  View details for Web of Science ID A1995RC42600002

  View details for PubMedID 7673657

• DELAYED-RESPONSE TO ANTIDEPRESSANTS IN DEPRESSED-PATIENTS WITH COMORBID ANXIETY Russell, J. M., Koran, L., Hirschfeld, R. M., McGee, M. D. ELSEVIER SCIENCE INC. 1995: 607–

  View details for Web of Science ID A1995QX03700056

• DOUBLE-BLIND PARALLEL COMPARISON OF 3 DOSAGES OF SERTRALINE AND PLACEBO IN OUTPATIENTS WITH OBSESSIVE-COMPULSIVE-DISORDER ARCHIVES OF GENERAL PSYCHIATRY Greist, J., Chouinard, G., DuBoff, E., Halaris, A., Kim, S. W., Koran, L., Liebowitz, M., Lydiard, R. B., Rasmussen, S., White, K., Sikes, C. 1995; 52 (4): 289-295

  Abstract

  Anecdotal evidence suggests patients with obsessive-compulsive disorder (OCD) are treated with selective serotonin uptake inhibitors at dosages significantly higher than those used with depressed patients. The current study examined the efficacy, safety, and optimal dosing strategy of sertraline in patients with OCD.Three hundred twenty-four nondepressed outpatients with OCD from 11 sites followed identical protocols using a double-blind parallel design. Following 1 week of single-blind placebo, patients were randomly assigned to 12 weeks of treatment with one of three fixed dosages of sertraline (50, 100, or 200 mg/d) or placebo.Sertraline patients exhibited significantly greater improvement (P < .05) at end point than placebo patients on all three main efficacy measures in the 50-mg/d and 200-mg/d groups and on one measure in the 100-mg/d group. The placebo response was larger in this population of subjects with OCD than in those previously studied. Adverse experiences were common in the sertraline and placebo groups and appeared to be dose-related in the sertraline-treated patients.Results support the safety and efficacy of daily dosages of 50, 100, and 200 mg of sertraline in the short-term treatment of patients with OCD.

  View details for Web of Science ID A1995QQ87500008

  View details for PubMedID 7702445

• DO SOFT SIGNS PREDICT TREATMENT OUTCOME IN OBSESSIVE-COMPULSIVE DISORDER JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES Thienemann, M., Koran, L. M. 1995; 7 (2): 218-222

  Abstract

  The authors examined 21 outpatients with obsessive-compulsive disorder for five neurological soft signs and abnormalities on two neuropsychological tests before and after 10 to 12 weeks of treatment with serotonin reuptake inhibitors. Patients showed a mean of 1.8 soft signs. Prevalences were finger-to-finger, 10%; adventitious movements, 29%; mirror movements, 33%; impaired cube drawing, 33%; and agraphesthesia, 76%. The Stroop Color and Word Test was abnormal in 10% and the Controlled Oral Word Association Test was abnormal in 14% of patients. Neither the presence of specific soft signs, the number of signs present, nor a combination of signs and test abnormalities predicted a poorer response to pharmacological treatment. Some baseline soft signs and abnormalities disappeared at endpoint in medication responders and nonresponders; no clear pattern of change emerged.

  View details for Web of Science ID A1995QV77600012

  View details for PubMedID 7626966

• Treating obsessive-compulsive disorder with serotonin reuptake inhibitors. Eur. Neuropsychopharmacol Koran LM 1995; 3 (5): 162-163
• CONTINUATION TREATMENT OF OCD - DOUBLE-BLIND AND OPEN-LABEL EXPERIENCE WITH FLUOXETINE Symposium on New Developments in the Treatment of OCD Tollefson, G. D., Birkett, M., Koran, L., GENDUSO, L. PHYSICIANS POSTGRADUATE PRESS. 1994: 69–78

  Abstract

  Recent advances in the pharmacotherapy of obsessive compulsive disorder (OCD) have led to a significant reduction in suffering and a return to productive living for many patients previously considered refractory to treatment. However, OCD can be a chronic disorder that significantly detracts from an individual's well-being. Potent inhibitors of 5-hydroxytryptamine (5-HT) reuptake have emerged as the first-line choice in the pharmacotherapy of OCD. These members of the therapeutic armamentarium for OCD, while associated with acute symptomatic improvement, have not been extensively studied during continuation therapy. In this study, 274 primary OCD subjects completed a 13-week, double-blind, placebo-controlled trial of three fixed doses of fluoxetine. Treatment responders (n = 76) continued their blinded treatment, whereas acute fixed-dose nonresponders began an open-label trial on their maximally tolerated dose (up to 80 mg daily) for 24 weeks. Responders maintained their acute treatment gains; in addition, all three doses of fluoxetine (20, 40, and 60 mg) were associated with further Y-BOCS improvement over the 24-week extension. Fluoxetine 60 mg achieved a statistically significantly greater reduction in Y-BOCS than placebo during the continuation. Open-label study subjects (n = 198) benefited from dose titration, with two thirds achieving a clinical response during the subsequent 24 weeks. Fluoxetine was well tolerated during both 24-week continuation periods. Only 4 (5.7%) of 70 subjects treated with fluoxetine in the responder extension terminated early due to an adverse event. The open-label extension, fluoxetine (to 80 mg), also demonstrated a low rate of adverse events; the profile of events was consistent with the extensive fluoxetine experience in other clinical populations. In conclusion, fluoxetine continuation treatment in OCD was associated with a maintained/improved symptomatic profile in most cases. Further dose titration improved the outcome of many acute, fixed-dose nonresponders. Continuation treatment with fluoxetine appeared to be well tolerated with few late-emergent adverse events.

  View details for Web of Science ID A1994PW78900007

  View details for PubMedID 7961535

• MAXIMIZING CLINICAL REVENUES OF PSYCHIATRIC CONSULTATION-LIAISON SERVICES - AN ECONOMIC COMMENTARY PSYCHOSOMATICS Koran, L. M., Foley, T. 1994; 35 (4): 333-340

  Abstract

  Clinical revenues rarely suffice to support an academic psychiatric consultation-liaison (C-L) service. Nonetheless, the revenue provides a major source of financial support. The authors describe ten steps that can help maximize the financial return from the C-L service's clinical efforts. The steps range from establishing a reasonable fee schedule and creating an efficient charge document, through educating residents and faculty physicians about documentation requirements, to billing quickly and insisting on meaningful monthly reports from the faculty practice plan. A number of "magic phrases" (proper and key wording for reimbursement) are described in detail that can markedly reduce documentation requirements.

  View details for Web of Science ID A1994NU44800001

  View details for PubMedID 8084984

• A MULTICENTER INVESTIGATION OF FIXED-DOSE FLUOXETINE IN THE TREATMENT OF OBSESSIVE-COMPULSIVE DISORDER ARCHIVES OF GENERAL PSYCHIATRY Tollefson, G. D., RAMPEY, A. H., Potvin, J. H., Jenike, M. A., Rush, A. J., Dominguez, R. A., Koran, L. M., Shear, M. K., Goodman, W., Genduso, L. A. 1994; 51 (7): 559-567

  Abstract

  To determine the effectiveness of fluoxetine hydrochloride at fixed doses of 20 mg/d, 40 mg/d, and 60 mg/d in patients with obsessive-compulsive disorder (OCD) and to evaluate its safety.Fixed-dose fluoxetine hydrochloride (20 mg/d, 40 mg/d, 60 mg/d) was compared with placebo in two randomized, double-blind, parallel, 13-week trials of identical design in 355 outpatients with OCD aged 15 to 70 years (DSM-III-R criteria; 1 year's duration or longer; depression secondary if present).Fluoxetine (all doses) was significantly (P < or = .001) superior to placebo on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score (mean baseline-to-end-point decrease, 4.6, 5.5, and 6.5 vs 0.9, respectively, studies pooled) and other efficacy measures (P < or = .01). A trend suggesting greater efficacy at 60 mg/d was observed. Most patients (79.2%) completed the study. Eight adverse events were statistically significantly more frequent with fluoxetine and one, with placebo. For some events, incidence tended to increase with increasing dosage; however, few patients discontinued treatment for any single event.Fluoxetine was associated with a statistically significant reduction in OCD severity, including time engaged in obsessional and/or compulsive behaviors. Adverse events infrequently led to study discontinuation.

  View details for Web of Science ID A1994NW19900010

  View details for PubMedID 8031229

• INTRAVENOUS CLOMIPRAMINE FOR OBSESSIVE-COMPULSIVE DISORDER JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Koran, L. M., Faravelli, C., Pallanti, S. 1994; 14 (3): 216-218

  View details for Web of Science ID A1994NL86900017

  View details for PubMedID 8027426

• ONE-YEAR FOLLOW-UP OF PSYCHOSOCIAL AND PHARMACOLOGICAL TREATMENTS FOR BULIMIA-NERVOSA JOURNAL OF CLINICAL PSYCHIATRY Agras, W. S., ROSSITER, E. M., ARNOW, Telch, C. F., Raeburn, S. D., Bruce, B., Koran, L. M. 1994; 55 (5): 179-183

  Abstract

  This study examined the outcome 1-year posttreatment of the use of desipramine, cognitive-behavioral therapy (CBT), and their combination in the treatment of bulimia nervosa.Sixty-one patients meeting DSM-III-R criteria for bulimia nervosa were randomly assigned to one of five groups--desipramine (withdrawn at 16 or 24 weeks), CBT (18 sessions), or the combined treatment (18 sessions of CBT plus desipramine withdrawn at 16 or 24 weeks)--and were followed to 1-year posttreatment.At 1-year follow-up, both the combined 24-week treatment and CBT alone were significantly superior in reducing binge eating to desipramine given for 16 weeks. The combined treatment was also superior to 16 weeks of desipramine in reducing emotionally driven eating and dietary restraint. Only 18% (2 of 11) of those receiving 16 weeks of desipramine were free of binge eating and purging at follow-up compared with 78% (7 of 9) of those receiving the combined 24-week treatment. The other groups fell between these two extremes.With the exception of the group treated for 16 weeks with desipramine alone, maintenance of improvement appeared satisfactory with all the treatments. Since the poorest results were found with 16 weeks of desipramine treatment, this study suggests that desipramine should be continued for at least 24 weeks either alone or combined with CBT. The broadest gain in reducing the psychopathology associated with bulimia nervosa was found with the combined 24-week treatment.

  View details for Web of Science ID A1994NQ97600001

  View details for PubMedID 8071266

• FLUOXETINE FOR ISOLATED SLEEP PARALYSIS PSYCHOSOMATICS Koran, L. M., Raghavan, S. 1993; 34 (2): 184-187

  View details for Web of Science ID A1993KP46100015

  View details for PubMedID 8456165

• A NATIONAL STUDY OF PSYCHIATRISTS PROFESSIONAL ACTIVITIES AMERICAN JOURNAL OF PSYCHIATRY Dorwart, R. A., CHARTOCK, L. R., Dial, T., Fenton, W., KNESPER, D., Koran, L. M., Leaf, P. J., Pincus, H., Smith, R., Weissman, S., WINKELMEYER, R. 1992; 149 (11): 1499-1505

  Abstract

  A mail survey was conducted in 1988-1989 to study the professional activities of U.S. psychiatrists. Data from the 19,431 active respondents are reported.Nineteen percent of the psychiatrists were women, an increase from the 17% reported in 1982. The median age of the respondents was 50 years. Nearly one-third of the respondents expressed interest in each of the following areas of subspecialization: adolescent psychiatry, substance abuse, geriatrics, and consultation-liaison psychiatry. More than one-fifth reported formal fellowship training in child/adolescent psychiatry. The psychiatrists worked an average of 48 hours per week--two-thirds in direct patient care--in an average of 2.3 different settings. The proportion of psychiatrists reporting private practice as their primary work setting showed a marked decline from 53% in 1982 to 45% in 1988. There was an increase from 4% in 1982 to 11% in 1988 in those whose primary work setting was a private psychiatric hospital. The typical caseload was over 60 patients, with roughly half that number seen each week. For inpatients treated, the two most common diagnoses were affective disorders and schizophrenic disorders. In a typical week psychiatrists treated about one-half of their outpatients with individual psychotherapy; three-fifths of these were also treated with medications. The average net income for psychiatrists working 35 hours or more per week was $99,850 for men and $73,174 for women.Major trends evident from this study are subspecialization, medicalization, privatization, feminization, and organizational diversification.

  View details for Web of Science ID A1992JV47600006

  View details for PubMedID 1357992

• EFFECTS OF OVARIECTOMY AND ESTROGEN REPLACEMENT ON DYE COUPLING AMONG RAT SUPRAOPTIC NUCLEUS NEURONS BRAIN RESEARCH Hatton, G. I., Yang, Q. Z., KORAN, L. E. 1992; 572 (1-2): 291-295

  Abstract

  Among magnocellular neurosecretory neurons (MNCs), the frequency of dye coupling, and thus also of electrotonic coupling, is reduced in male rats following castration. Testosterone replacement prevented this reduction suggesting a modulatory role for gonadal steroids. To determine whether gonadal steroids in females influenced coupling incidence, Lucifer yellow CH injections were made in MNCs in slices taken from ovariectomized rats, either untreated or implanted with capsules containing estradiol-17 beta or estradiol-17 alpha, or from sham operated rats. In groups without biologically active estradiol, incidence of dye coupling was increased by 138-169% over those with normal plasma levels, as measured by radioimmunoassay. We conclude that estradiol and testosterone have opposite effects on coupling frequency among MNCs and that the facilitatory effects of testosterone in males are unlikely to be via its aromatization to estrogen.

  View details for Web of Science ID A1992HE98800045

  View details for PubMedID 1611526

• FLUOXETINE FOR TRICHOTILLOMANIA - AN OPEN CLINICAL-TRIAL PSYCHOPHARMACOLOGY BULLETIN Koran, L. M., RINGOLD, A., Hewlett, W. 1992; 28 (2): 145-149

  Abstract

  Of 17 adult patients with long-standing trichotillomania, 13 completed an 8- to 12-week open trial of fluoxetine, up to 80 mg per day. No patient had obsessive-compulsive disorder or major depression. We used the compulsions subscale of the Yale-Brown Obsessive-Compulsive Scale (YBOCS) to rate patients' hair-pulling behavior. The 13 completing patients' mean YBOCS score decreased significantly from 10.15 at baseline to 5.92 at the completion visit (Student's paired t = 4.82, df = 12, two-tailed p less than .001). Of these 13 patients, 5 experienced a 50 percent or greater decrease in their pulling behavior as measured by the YBOCS; 4 experienced between a 25 percent and 50 percent decrease. Three of the patients stopped pulling entirely, as did 2 of the 4 noncompleting patients. Three noncompleting patients discontinued treatment because of side effects, and 1 insisted on early use of behavior therapy. Comparative treatment trials elucidating the indications, risks, and expectable benefits of psychotherapeutic and pharmacological treatments are needed.

  View details for Web of Science ID A1992JG20100005

  View details for PubMedID 1513916

• FUNDING CONSULTATION-LIAISON PSYCHIATRY VIA MEDICARE SCREENING GENERAL HOSPITAL PSYCHIATRY Koran, L. M. 1992; 14 (1): 7-14

  Abstract

  Despite offering many benefits to patients, the hospital, and the hospital staff, an academic psychiatric consultation service is difficult to fund. By screening Medicare patients for psychiatric complications and comorbid conditions, the consultation-liaison (C-L) service can generate incremental revenue for the hospital by moving patients from lower-paying to higher-paying Diagnostic Related Groups (DRGs). The C-L service chief can negotiate with the hospital to obtain a portion of these incremental funds to support the C-L service. Concurrent psychiatric disorders that move patients to more complex DRGs include substance abuse, substance dependence, drug-induced delirium, drug-induced organic affective syndrome, and psychotic depression. This paper presents a method of calculating the incremental hospital revenue generated by such screening along with the results of applying the method to selected DRGs at a west coast teaching hospital. Implementing this program at that hospital in fiscal year 1989 would have resulted in screening 142 Medicare patients (2.2% of Medicare admissions), discovering an estimated 25 patients with comorbid psychiatric conditions, and generating $51,800 in incremental hospital revenue. In creating a screening program, a C-L service chief must be prepared to negotiate issues with the medical records department, referring physicians, and the hospital administration.

  View details for Web of Science ID A1992GW53100003

  View details for PubMedID 1730404

• PHARMACOLOGICAL AND COGNITIVE-BEHAVIORAL TREATMENT FOR BULIMIA-NERVOSA - A CONTROLLED COMPARISON AMERICAN JOURNAL OF PSYCHIATRY Agras, W. S., ROSSITER, E. M., Arnow, B., Schneider, J. A., Telch, C. F., Raeburn, S. D., Bruce, B., Perl, M., Koran, L. M. 1992; 149 (1): 82-87

  Abstract

  This study examined the relative effectiveness of desipramine, cognitive-behavioral therapy, and their combination in the treatment of bulimia nervosa, together with the effects of withdrawing medication after two different lengths of treatment.Seventy-one patients meeting DSM-III-R criteria for bulimia nervosa, recruited from an eating disorders clinic or by advertisements, were assigned at random to one of five groups: desipramine (withdrawn at 16 or 24 weeks), combined treatment (medication withdrawn at 16 or 24 weeks), and cognitive-behavioral therapy (15 sessions). All treatments were conducted individually in an outpatient clinic. The primary outcome measures were binge eating and purging rates assessed at pretreatment, 16, 24, and 32 weeks. The results were analyzed as three groups (medication, cognitive-behavioral therapy, and combined treatment) at 16 weeks and as five groups at subsequent assessments.At 16 weeks, both cognitive-behavioral therapy and the combined treatment were superior to medication given for 16 weeks in reducing binge eating and purging. At 32 weeks, however, only the combined 24-week treatment was superior to medication given for 16 weeks. The combined treatment was also more effective in reducing dietary preoccupation and hunger. Continuing cognitive-behavioral therapy appeared to prevent relapse in patients withdrawn from medication at 16 weeks.Overall, the results favor the use of a combination of medication and cognitive-behavioral therapy in the treatment of bulimia nervosa, with medication continued for at least 24 weeks.

  View details for Web of Science ID A1992GX04000012

  View details for PubMedID 1728190

• A PROFILE OF ACADEMIC MEDICAL PSYCHIATRIC UNITS GENERAL HOSPITAL PSYCHIATRY Harsch, H. H., Koran, L. M., Young, L. D. 1991; 13 (5): 291-295

  Abstract

  Medical-psychiatric inpatient programs are a relatively recent phenomenon. Although interest in these programs seems widespread, they are still found primarily at academic medical centers. The authors surveyed 11 such academic units. Variations found between their patient populations, milieu, and organization suggest that these programs, in general, are still in an early stage of evolution. It is hoped that these data will provide a descriptive base of how these programs have developed.

  View details for Web of Science ID A1991GG58100002

  View details for PubMedID 1743497

• TIME COURSE OF SALAMANDER SPINAL-CORD REGENERATION AND RECOVERY OF SWIMMING - HRP RETROGRADE PATHWAY TRACING AND KINEMATIC ANALYSIS EXPERIMENTAL NEUROLOGY DAVIS, B. M., AYERS, J. L., Koran, L., Carlson, J., Anderson, M. C., Simpson, S. B. 1990; 108 (3): 198-213

  Abstract

  The time course of regeneration of supraspinal and descending brachial intraspinal axons was studied using HRP retrograde tracing and kinematic analysis. Five groups of salamanders (10 salamanders/group) received complete thoracic transection 1.0 cm rostral to the hind limbs abolishing swimming. Groups 1-4 recovered for 2, 4, 6, and 8 weeks, respectively, before being filmed to record the animal's ability to swim. After filming, a second transection was made 1.0 cm caudal to the first (at the level of the lumbar enlargement) and HRP was used to label descending axons which had grown past the first lesion. The fifth group was filmed every 2 weeks for 12 weeks before the second transection was made for HRP application. The films were used to perform frame by frame computer analysis of the amplitude and timing of cyclic lateral flexion waves which make up swimming behavior. The earliest return of coordinated swimming behavior was seen 4 weeks after transection (1 of 20 animals). At 6 weeks post-transection, 5 of 10 animals exhibited coordinated swimming. However, the behavior in these animals was subnormal. In the group surviving 8 weeks post-transection, 5 of 10 animals recovered coordinated swimming behavior. In the group that was filmed every 2 weeks, 5 of the 10 salamanders which did recover, exhibited coordinated swimming behavior by the eighth week post-transection. Kinematic analysis of salamanders that exhibited a return of coordinated swimming revealed quantitative differences compared to normal salamanders. While continuous head to tail undulatory waves were present, the propagation time and period were faster than those in normal salamanders. Retransection of the spinal cord abolished coordinated swimming. The numbers and distribution of HRP-labeled supraspinal neurons varied greatly among the animals that displayed recovery of locomotor abilities. In the salamanders examined 6 weeks post-transection the majority of labeled cells were found in medullary nuclei. In recovered salamanders examined 8 and 12 weeks post-transection, HRP-labeled neurons were found in the red nucleus, in the interstitial nucleus of the fasciculus longitudinalis medialis, and in the mesencephalic as well as the medullary reticular neurons. Recovery of coordinated swimming was only observed in salamanders in which descending supraspinal and intraspinal axons were present at the level of the lumbar enlargement (as demonstrated by HRP retrograde labeling). These results indicate that recovery of locomotion is dependent on the reestablishment of descending input and is not a result of changes in spinal reflexes or propagation of electrical activity through the body wall.

  View details for Web of Science ID A1990DK24200002

  View details for PubMedID 2351209

• A MEDICAL ALGORITHM FOR DETECTING PHYSICAL DISEASE IN PSYCHIATRIC-PATIENTS HOSPITAL AND COMMUNITY PSYCHIATRY Sox, H. C., Koran, L. M., Sox, C. H., Marton, K. I., DUGGER, F., Smith, T. 1989; 40 (12): 1270-1276

  Abstract

  An algorithm for screening psychiatric patients for physical disease was empirically derived from a comprehensive assessment of 509 patients in California's mental health system. The first 343 patients were used to develop the algorithm, and the remaining 166 were used as a test group. Calculations were made for several versions of the algorithm, and the data were compared with the diagnoses listed in the patients' admission mental health record. The algorithmic procedure was more accurate and more cost-effective than the medical evaluation procedures used by the state mental health system. When applied to the test group, the algorithm detected up to 90 percent of patients who had an active, important physical disease at a cost of $156 per patient. The mental health system had detected 58 percent of test-group patients with a disease at a cost of $230 per patient.

  View details for Web of Science ID A1989CC17600008

  View details for PubMedID 2512242

• Medical evaluation of psychiatric patients. I. Results in a state mental health system. Archives of general psychiatry Koran, L. M., Sox, H. C., Marton, K. I., MOLTZEN, S., Sox, C. H., Kraemer, H. C., Imai, K., Kelsey, T. G., Rose, T. G., LEVIN, L. C. 1989; 46 (8): 733-740

  Abstract

  Thorough medical evaluation of 529 patients drawn from eight program categories in California's public mental health system revealed active, important physical disease in 200 patients who had 291 diseases. Fourteen percent of the patients had diseases known to themselves but not to the mental health system, and 12% of the patients had diseases newly detected by the study team. We estimate that of the more than 300,000 patients treated in the California public mental health system in fiscal year 1983 to 1984, 45% had an active, important physical disease. The mental health system had recognized only 47% of study patients' physical diseases, including 32 of 38 diseases causing a mental disorder and 23 of 51 diseases exacerbating a mental disorder. Patients treated in public sector mental health facilities should receive careful medical evaluations.

  View details for PubMedID 2787623

• MEDICAL EVALUATION OF PSYCHIATRIC-PATIENTS .1. RESULTS IN A STATE MENTAL-HEALTH SYSTEM ARCHIVES OF GENERAL PSYCHIATRY Koran, L. M., Sox, H. C., Marton, K. I., MOLTZEN, S., Sox, C. H., Kraemer, H. C., Imai, K., Kelsey, T. G., ROSE, T. G., LEVIN, L. C., Chandra, S. 1989; 46 (8): 733-740

  View details for Web of Science ID A1989AJ47500007

• HOUSE STAFF WELL-BEING WESTERN JOURNAL OF MEDICINE Koran, L. M., Litt, I. F. 1988; 148 (1): 97-101

  Abstract

  From a survey of 281 house-staff members of a university medical center, we found that nearly half the respondents were afraid to complain about their training programs and were concerned that their relationship with their partner would not survive the residency. In all, 40% reported that anxiety or depression impaired their performance for a month or more; 12% reported an increased use of alcohol, marijuana, or cocaine; and 7% an increased use of sedatives, stimulants, or opioids. Stressors and dysfunctional behaviors did not differ significantly between male and female house staff, but many women had more tenuous support systems. Married house staff had stronger support systems and less substance abuse, anxiety, and depression. Departments differed widely in house-staff morale, available social supports, and the frequency of dysfunctional behaviors. Residency program directors should assess their house staff's distress and study and initiate means to reduce stress, increase support, and facilitate coping.

  View details for Web of Science ID A1988L724600033

  View details for PubMedID 3341147

• DETECTING PHYSICAL DISEASE IN PSYCHIATRIC-PATIENTS MEDICAL CARE Koran, L. M., Sox, H. C., Sox, C. H., Marton, K. I. 1987; 25 (12): S99-S99

  View details for Web of Science ID A1987L519300010

  View details for PubMedID 3123814

• MOBILE MEDICAL SCREENING TEAMS FOR PUBLIC PROGRAMS HOSPITAL AND COMMUNITY PSYCHIATRY Koran, L. M., Sox, H. C., Marton, K. I. 1984; 35 (11): 1151-1152

  View details for Web of Science ID A1984TR27500014

  View details for PubMedID 6500530

• SOCIAL-INDICATORS IN STATEWIDE MENTAL-HEALTH PLANNING - LESSONS FROM CALIFORNIA SOCIAL INDICATORS RESEARCH Koran, L. M., MEINHARDT, K. 1984; 15 (2): 131-144

  View details for Web of Science ID A1984TH48500003

• DETECTING PHYSICAL ILLNESS IN PATIENTS WITH MENTAL-DISORDERS PSYCHOSOMATICS Hoffman, R. S., Koran, L. M. 1984; 25 (9): 654-660

  View details for Web of Science ID A1984TJ99800001

  View details for PubMedID 6494402

• CHANGING HOSPITAL WORK ENVIRONMENTS - AN EXAMPLE OF A BURN UNIT GENERAL HOSPITAL PSYCHIATRY Koran, L. M., Moos, R. H., Moos, B., ZASSLOW, M. 1983; 5 (1): 7-13

  Abstract

  A liaison psychiatrist invited to help a burn unit staff explore problems affecting morale and patient care employed a four-step procedure: (1) assess the work environment systematically; (2) give the staff feedback from this assessment; (3) help the staff plan and institute changes; and (4) reassess. To assess the work environment, the staff completed the Work Environment Scale (WES), a 90-item, true/false questionnaire that measures ten dimensions of the actual and preferred work environment. At the second of 12 bi-weekly meetings, the psychiatrist presented the unit's WES profile and began helping the staff explore and resolve problems. Reassessment six months later revealed statistically significant changes on several pertinent WES scales and reduced discrepancies between actual and preferred work environments on nine of the ten scales. The findings indicate that systemmatic assessment and feedback procedures may help liaison programs improve the quality of hospital work environments and thereby enhance staff performance and morale.

  View details for Web of Science ID A1983QK48200002

  View details for PubMedID 6840546

• LITHIUM PROPHYLAXIS OF PREDNISONE PSYCHOSIS - A CASE-REPORT JOURNAL OF CLINICAL PSYCHIATRY GOGGANS, F. C., WEISBERG, L. J., Koran, L. M. 1983; 44 (3): 111-112

  Abstract

  The authors describe a case in which lithium may have prevented a relapse of prednisone-related psychosis in a patient who required chronic steroid therapy for severe pulmonary disease. The literature supporting the use of lithium for this indication is reviewed and suggestions for further research are made.

  View details for Web of Science ID A1983QG28800009

  View details for PubMedID 6403514

• RECRUITMENT OF INSTITUTIONAL PSYCHIATRISTS FOR THE 50-STATES SOCIAL SCIENCE & MEDICINE Koran, L. M., Chinn, F., Flores, S. 1983; 17 (13): 889-896

  Abstract

  We studied institutional recruitment of non-federal psychiatrists in 1979 as measured by national advertisements. Vacant positions in state mental hospitals and CMHCs are over-represented in the adverts compared to the current institutional distribution of physicians practicing psychiatry. States' per capita recruitment rates vary widely, but do not decrease linearly or exponentially with increasing abundance of psychiatrists. The percentage increase sought in institutional psychiatrists ('recruitment intensity'), however, does decrease exponentially as institutional psychiatrists/100,000 population increase. Recruitment rates and recruitment intensity are not highly correlated with states' sociodemographic characteristics or with characteristics of their health care systems. Private sector recruitment, however, is significantly higher in states that have mandated psychiatric benefit packages in private insurance. Studies relating institutional recruitment or vacancy rates to measures of local demand for psychiatric services are needed, as well as comparisons of successful versus unsuccessful institutions. Institutional vacancies are undoubtedly affecting the quality of care, compliance with standards for reimbursement and ability to generate third-party revenues. Greater understanding of institutional recruitment is needed.

  View details for Web of Science ID A1983QZ30100006

  View details for PubMedID 6612376

• PSYCHIATRISTS DISTRIBUTION ACROSS THE 50 STATES, 1978 ARCHIVES OF GENERAL PSYCHIATRY Koran, L. M. 1981; 38 (10): 1155-1159

  Abstract

  In 1978, both psychiatrists and a nonmedical professional group (lawyers) were more abundant in more populous, urbanized states. Lawyer-population ratios, however, correlated more strongly with the population's wealth; psychiatrist-population ratios correlated more strongly with the percentage of state population with college education and with state-mandated private insurance coverage of psychiatric services (both probable indexes of market demand). Even after controlling for population size and education, state-mandated insurance coverage was significantly related to the abundance of psychiatrist. Moreover, mandating states increased their psychiatrist-population ratios 100% faster after mandating coverage, whereas nonmandating states increased their ratios only 25% faster in comparable periods. While we investigate psychiatrists' geographic distribution, public policy formation can be aided if we also seek better measures of access and barriers to psychiatric care.

  View details for Web of Science ID A1981ML87400010

  View details for PubMedID 7027989

• MENTAL-HEALTH EXPENDITURES IN CALIFORNIA COUNTIES AMERICAN JOURNAL OF PSYCHIATRY Koran, L. M., MEINHARDT, K. 1981; 138 (7): 936-940

  Abstract

  In 1957 California began placing responsibility for public mental health services on county programs still vary widely in emphasis and size. The authors explored determinants of counties' unequal program developments using per capita expenditures as the measure of county services. Sociodemographic variables that help explain states' social program expenditures correlate weakly or not at all with county mental health expenditures. The most powerful predictor of these expenditures is number of psychiatrists per 10,000 population. Equal per capita expenditures, however, are not a reasonable goal; these can mask wide variations in program content, efficiency, and quality of care.

  View details for Web of Science ID A1981LW05800009

  View details for PubMedID 7258353

• PSYCHIATRIC MANPOWER RATIOS - BEGUILING NUMBERS GAME ARCHIVES OF GENERAL PSYCHIATRY Koran, L. M. 1979; 36 (13): 1409-1415

  Abstract

  Many characteristics of California's counties that correlate with physician-population ratios also correlate with psychiatrist-population ratios, with their changes through time and with rural counties' ability to attract psychiatrists. These same county characteristics seem to influence the uneven distribution of lawyers throughout the state, a fact that should help physicians help legislators understand problems in attempting to equalize manpower distribution. California's relatively high psychiatrist-population ratio and the presence of counties that are statistically anomalous should preclude the application of these findings to other states. Despite government interest in psychiatrist-population ratios as a device to estimate manpower needs, these ratios are a poor measure of access to services. Barriers to care such as lack of private insurance coverage and Medicaid and Medicare restrictions appear more powerful than uneven manpower distribution. Proposals for influencing psychiatrists' distribution should be compared with other methods of decreasing mental illness morbidity, such as mandating insurance coverage and increasing funds for preventive services and research.

  View details for Web of Science ID A1979HZ71800003

  View details for PubMedID 518242

• PATIENTS REACTIONS TO PSYCHIATRIC-CONSULTATION JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Koran, L. M., VANNATTA, J., Stephens, J. R., Pascualy, R. 1979; 241 (15): 1603-1605

  Abstract

  Physicians are often concerned that patients will resent a request for psychiatric consultation. To investigate this problem, 60 patients undergoing psychiatric consultation in a general hospital were inverviewed 24 hours after the consultation. Nearly two thirds of these patients believed that the consultation was beneficial. Patients' attitudes were independent of their demographic characteristics, reason for referral, and hospital service involved. Patients with long-term illnesses more often had positive attitudes than patients with short-term illnesses. Patients who were initially hostile or ambivalent usually had positive attitudes 24 hours later. Substance abusers and patients who denied clearly recognizable psychiatric disorders often did not value the consultation. Even so, their physicians frequently believed that the consultation was useful. We attribute the positive attitudes of patients in our study largely to the referring physicians' preparing them for psychiatric consultation.

  View details for Web of Science ID A1979GR17200016

  View details for PubMedID 430714

• Psychosocial considerations are compatible with the biomedical model. Man and medicine Gonda, T. A., Koran, L. M. 1979; 4 (4): 279-285

  View details for PubMedID 550028

• EVALUATION OF A VIDEOTAPE TECHNIQUE FOR MEASURING CLINICAL PSYCHIATRIC SKILLS OF MEDICAL-STUDENTS JOURNAL OF MEDICAL EDUCATION Tardiff, K., Redfield, J., Koran, L. M. 1978; 53 (5): 438-441

  View details for Web of Science ID A1978FA20400017

  View details for PubMedID 77903

• TEACHING MEDICAL-STUDENTS ABOUT OBSERVER VARIATION JOURNAL OF MEDICAL EDUCATION Koran, L. M., HAHN, P. M., VARMA, A. A., White, L. 1978; 53 (2): 141-144

  View details for Web of Science ID A1978EL88200012

  View details for PubMedID 75974

• ORGANIC-DISEASE MISTAKENLY DIAGNOSED AS PSYCHIATRIC PSYCHOSOMATICS Saravay, S. M., Koran, L. M. 1977; 18 (2): 6-11

  View details for Web of Science ID A1977DK73400001

  View details for PubMedID 877201

• GAMMA-AMINOBUTYRIC-ACID DEFICIENCY IN SCHIZOPHRENIA LANCET Koran, L. M. 1976; 2 (7993): 1025-1025

  View details for Web of Science ID A1976CJ73800036

  View details for PubMedID 62243

• MENTAL-HEALTH SERVICES IN PUBLIC AND PRIVATE SECTORS AMERICAN JOURNAL OF PSYCHIATRY Koran, L. M. 1976; 133 (9): 1052-1057

  Abstract

  Analysis of data on mental health service providers indicates that in 1971 the private sector accounted for 34% of inpatient days, 86% of outpatient visits, 44% of expenditures by source of funds, and 51% of expenditures by receipt of funds. The author believes that mental health professionals must familiarize themselves with the economic interests influencing national health insurance proposals and with public policy making processes if they are to help preserve appropriate roles for the public and private sectors in mental health service delivery.

  View details for Web of Science ID A1976CC45000011

  View details for PubMedID 961927

• CLINICAL SKILLS - QUANTITATIVE MEASUREMENT NEW YORK STATE JOURNAL OF MEDICINE Wiener, S. L., Koran, L., Mitchell, P., SCHATTNER, G., Fierstein, J., Hotchkiss, E. 1976; 76 (4): 610-612

  View details for Web of Science ID A1976BM69900019

  View details for PubMedID 1063308

• INCREASING RELIABILITY OF CLINICAL DATA AND JUDGMENTS ANNALS OF CLINICAL RESEARCH Koran, L. M. 1976; 8 (2): 69-73

  View details for Web of Science ID A1976BT60300001

  View details for PubMedID 937997

• RELIABILITY OF CLINICAL METHODS, DATA AND JUDGMENTS .2. NEW ENGLAND JOURNAL OF MEDICINE Koran, L. M. 1975; 293 (14): 695-701

  View details for Web of Science ID A1975AR36700005

  View details for PubMedID 1160937

• PUBLIC HYSTERIA AND MEDICAL-PRACTICE JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Koran, L., Fink, M., Miller, M. G. 1975; 232 (11): 1126-1126

  View details for Web of Science ID A1975AE68100005

  View details for PubMedID 1173610

• RELIABILITY OF CLINICAL METHODS, DATA AND JUDGMENTS .1. NEW ENGLAND JOURNAL OF MEDICINE Koran, L. M. 1975; 293 (13): 642-646

  View details for Web of Science ID A1975AQ70600007

  View details for PubMedID 1097917

• CONTROVERSY IN MEDICINE AND PSYCHIATRY AMERICAN JOURNAL OF PSYCHIATRY Koran, L. M. 1975; 132 (10): 1064-1066

  Abstract

  Factual and ethical controversies confront physicians in medicine as well as in psychiatry. If psychiatrists can impart a perspective on these controversies and their growth-stimulating quality to medical students and thereby increase their tolerance for uncertainty, they will aid them in becoming better physicians and will perhaps also remove one reason for their disinterest in psychiatry.

  View details for Web of Science ID A1975AS01300014

  View details for PubMedID 1166879

• HEROIN MAINTENANCE FOR HEROIN ADDICTS - ISSUES AND EVIDENCE NEW ENGLAND JOURNAL OF MEDICINE Koran, L. M. 1973; 288 (13): 654-660

  View details for Web of Science ID A1973P157000005

  View details for PubMedID 4568989

• EARLY TERMINATION FROM GROUP PSYCHOTHERAPY INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY Koran, L. M., COSTELL, R. M. 1973; 23 (3): 346-359

  View details for Web of Science ID A1973Q371100009

  View details for PubMedID 4733358

• [Treatment of drug addicts with narcotic and non-narcotic drugs]. Bulletin de la Société des sciences médicales du Grand-Duché de Luxembourg Koran, L. M. 1972; 109 (1): 67-73

  View details for PubMedID 5056099

• RESULTS IN TREATMENT OF NARCOTICS USERS BULLETIN DE LA SOCIETE DES SCIENCES MEDICALES DU GRAND-DUCHE DE LUXEMBOURG KORAN, L. N. 1972: 77-?

  View details for Web of Science ID A1972M475700009

  View details for PubMedID 5056100

• PSYCHIATRY IN MAINLAND CHINA - HISTORY AND RECENT STATUS AMERICAN JOURNAL OF PSYCHIATRY Koran, L. M. 1972; 128 (8): 970-?

  View details for Web of Science ID A1972L483500009

  View details for PubMedID 4550732

• FIELD DEPENDENCE IN MANIC-DEPRESSIVE PATIENTS JOURNAL OF NERVOUS AND MENTAL DISEASE Koran, L. M., MAXIM, P. E. 1972; 155 (3): 205-?

  View details for Web of Science ID A1972N471700007

  View details for PubMedID 4559854

• COMPATIBILITY AND COHESIVENESS IN GROUP PSYCHOTHERAPY - RE-EVALUATION AND EXTENSION JOURNAL OF NERVOUS AND MENTAL DISEASE COSTELL, R. M., Koran, L. M. 1972; 155 (2): 99-?

  View details for Web of Science ID A1972N274900003

  View details for PubMedID 5050731

• PSYCHIATRY IN MAINLAND CHINA - ADDITIONAL SOURCES AMERICAN JOURNAL OF PSYCHIATRY Kleinman, A. M. 1972; 129 (4): 482-?

  View details for Web of Science ID A1972N628500022

  View details for PubMedID 4561020