- Electroconvulsive Therapy
- Transcranial Magnetic Stimulation
Clinical Professor, Psychiatry and Behavioral Sciences
Medical Director, Interventional Psychiatric Therapies (2003 - 2010)
Honors & Awards
Academic Teaching Award, San Mateo County Residency Training Program (June 15, 2003)
Academic Teaching Award, Stanford Department of Psychiatry (June 18, 2001)
George D Gulevic MD Award, Stanford Department of Psychiatry (June 21, 1997)
Laughlin Fellow, American College of Psychiatrists (1997)
PhD Training:University of Alabama School of Medicine (1989) AL
Board Certification: Psychiatry, American Board of Psychiatry and Neurology (2001)
Fellowship:Stanford University School of Medicine Registrar (1998) CA
Residency:Stanford University School of Medicine Registrar (1997) CA
Internship:Stanford University Medical Center (1994) CA
Medical Education:University of Alabama School of Medicine (1993) AL
PhD, Univ Alabama at Birmingham, Cell and Molecular Biology (1989)
Community and International Work
Orphans and Vulnerable Children in Sub Saharan Africa, Zimbabwe, Namibia
Biological and psychological well-being assessments
Child Protection Society, Zimbabwe
orphans and vulnerable children
Opportunities for Student Involvement
Current Research and Scholarly Interests
My work is focused on novel interventional treatment approaches for treatment resistant unipolar and bipolar depression. We are currently enrolling patients with treatment refractory bipolar depression for a radiosurgical neuromodulation study. We are awaiting the start of enrollment for a DBS in unipolar depression study.
I am also working with children in Sub Saharan Africa. Primarily I am focused on methods to assess well-being, and long term outcomes for these vulnerable children.
International Study to Predict Optimised Treatment - in Depression
The aim of this study is to identify genetic, physical (brain) and psychological (cognitive) markers (or combinations of them) that predict specific response to a range of antidepressants treatment (Escitalopram, Venlafaxine, Sertraline) in patients diagnosed with major depressive disorder. This study is focused on outcomes which may impact on how "personalised medicine" is implemented in depression.
24-week Placebo-controlled Trial of Flibanserin Once Daily in Premenopausal Women With Hypoactive Sexual Desire Disorder
This trial is designed to assess the safety and efficacy of flibanserin in the treatment of premenopausal women with Hypoactive Sexual Desire Disorder (HSDD) that meets standard diagnostic criteria. Efficacy for flibanserin will be assessed vs. a parallel placebo group.
Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Howden, (650) 498 - 6128.
Investigate Efficacy & Safety of RO4995819 vs. Placebo as Adjunct Tx in Patients w/Major Depressive Disorder
The purpose of the study is to explore the efficacy of 6 weeks treatment of an investigational medication, RO4995819, versus placebo as adjunctive therapy in patients with major depression.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Chang, B.S., 650-725-4620.
Mifepristone in Refractory Depression
The purpose of the study is to examine the effectiveness of mifepristone treatment in patients with refractory depression. Refractory depression is defined as clinical depression that is unimproved after treatment with at least 2 different antidepressants of adequate dose and time trial. Mifepristone will augment current medications.
Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Keller, (650) 724 - 0070.
Mifepristone Treatment for Patients With Non-psychotic Major Depressive Disorder Receiving Bilateral ECT
The purpose of this study is to see whether the medication mifepristone is an effective and tolerable treatment for increasing the clinical effectiveness of electroconvulsive therapy (ECT) and protecting cognitive function during ECT. Both Mifepristone and ECT appear to normalize hyperfunctioning of the hypothalmic-pituitary-adrenal (HPA) axis, which has been found among patients with major depression referred for ECT. The combination of these two treatments in major depression may lead to a more rapid clinical response than ECT alone. Additionally, there appears to be a connection between pre-ECT higher cortisol levels due to HPA axis hyperfunctioning and post-ECT cognitive impairment. Administration of mifepristone prior to and during ECT treatment may reduce cortisol levels and reduce the incidence of cognitive impairment observed after ECT.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Chang, (650) 725 - 4620.
Radiosurgical Neuromodulation for Refractory Depression
This study is designed to evaluate the safety and effectiveness of an investigational procedure for treating people with treatment resistant bipolar depression (TRD). Precise dose delivery of radiation to the predetermined targets in the brain will be accomplished with known Cyberknife stereotactic radiosurgery methods. This technology is considered to be noninvasive (does not physically invade your body). We will be studying if the Cyberknife influences the sensitivity of certain nerves of your brain. Although many clinical treatments for psychiatric conditions have been done using stereotactic radiosurgery, the present study is experimental, because we are seeking to use more moderate doses of radiation that are intended not to destroy any brain cells, but to normalize or modulate their function.
Stanford is currently not accepting patients for this trial. For more information, please contact Jessica Hawkins, (650) 723 - 8323.
Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment Resistant Bipolar Depression
We hope to learn whether this stimulation of neurons in the front part of the brain may relieve depression.
Stanford is currently not accepting patients for this trial. For more information, please contact Jessica Hawkins, (650) 723 - 8323.
Treatment of Schizoaffective Disorder Using Mifepristone
This study tests the hypothesis that mifepristone will diminish cognitive distortion and alleviate psychosis in patients with schizoaffective disorder.
Stanford is currently not accepting patients for this trial. For more information, please contact Jessica Hawkins, (650) 723 - 8323.
- Neurobiology of Depression:Why Depression Is A Brain Disorder And How Brain Stimulation May Treat It
PSYC 84Q (Win)
- Independent Studies (5)
Coping with the challenges of living in an Indonesian residential institution
2010; 96 (1): 45-50
The aim of this study was to describe challenges and strategies for coping with these challenges among individuals living in an institutional setting.This study used a qualitative approach to analyze the interviews of fourteen participants (11 males and 3 females) ages 10-24 residing in an Indonesian residential institution (orphanage and Muslim boarding school).Insufficient access to educational resources and basic necessities were major concerns of the participants, as was the residential institution's unresponsiveness and the lack of connection experienced by residents. Individuals coped with these challenges by turning to others for social support and by trying to change the focus of their thoughts, such as to more pleasant thoughts or simply to mentally disengage.Some youths and young adults residing in institutions such as a residential institution demonstrate resilience at the individual level by utilizing coping strategies to address problems in obtaining adequate educational, material and psychological support. However, because inadequacies in these kinds of support ultimately impede psychosocial development, it is imperative to develop solutions for addressing these problems at the institutional and societal level rather than at the level of individual youths and young adults.
View details for DOI 10.1016/j.healthpol.2010.01.001
View details for Web of Science ID 000279096300007
View details for PubMedID 20102784
- Reply regarding "efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial". Biological psychiatry 2010; 67 (2): e15-7
Cognitive Behavioral Analysis System of Psychotherapy and Brief Supportive Psychotherapy for Augmentation of Antidepressant Nonresponse in Chronic Depression
ARCHIVES OF GENERAL PSYCHIATRY
2009; 66 (11): 1178-1188
Previous studies have found that few chronically depressed patients remit with antidepressant medications alone.To determine the role of adjunctive psychotherapy in the treatment of chronically depressed patients with less than complete response to an initial medication trial.This trial compared 12 weeks of (1) continued pharmacotherapy and augmentation with cognitive behavioral analysis system of psychotherapy (CBASP), (2) continued pharmacotherapy and augmentation with brief supportive psychotherapy (BSP), and (3) continued optimized pharmacotherapy (MEDS) alone. We hypothesized that adding CBASP would produce higher rates of response and remission than adding BSP or continuing MEDS alone.Eight academic sites.Chronically depressed patients with a current DSM-IV-defined major depressive episode and persistent depressive symptoms for more than 2 years.Phase 1 consisted of open-label, algorithm-guided treatment for 12 weeks based on a history of antidepressant response. Patients not achieving remission received next-step pharmacotherapy options with or without adjunctive psychotherapy (phase 2). Individuals undergoing psychotherapy were randomized to receive either CBASP or BSP stratified by phase 1 response, ie, as nonresponders (NRs) or partial responders (PRs).Proportions of remitters, PRs, and NRs and change on Hamilton Scale for Depression (HAM-D) scores.In all, 808 participants entered phase 1, of which 491 were classified as NRs or PRs and entered phase 2 (200 received CBASP and MEDS, 195 received BSP and MEDS, and 96 received MEDS only). Mean HAM-D scores dropped from 25.9 to 17.7 in NRs and from 15.2 to 9.9 in PRs. No statistically significant differences emerged among the 3 treatment groups in the proportions of phase 2 remission (15.0%), partial response (22.5%), and nonresponse (62.5%) or in changes on HAM-D scores.Although 37.5% of the participants experienced partial response or remitted in phase 2, neither form of adjunctive psychotherapy significantly improved outcomes over that of a flexible, individualized pharmacotherapy regimen alone. A longitudinal assessment of later-emerging benefits is ongoing.
View details for Web of Science ID 000271427500004
View details for PubMedID 19884606
View details for PubMedCentralID PMC3512199
Effects of major depression diagnosis and cortisol levels on indices of neurocognitive function
2009; 34 (7): 1012-1018
Although many studies have examined separately the effects of depression and cortisol on cognition, no study has examined their relative or potentially additive effects. Our study simultaneously investigated the contributions of clinical status [major depression (MD) versus psychiatrically healthy controls (HC)] and cortisol on a hippocampal/mediotemporal mediated verbal memory task (Paragraph Recall) and a prefrontal cortex/cingulate mediated executive functioning task (Stroop). Thirty-seven unmedicated nondelusional MDs and 18 HCs underwent psychiatric ratings, hourly assessments of cortisol activity over 24 h, and neuropsychological assessments. Hierarchical multiple regressions indicated a significant effect of cortisol but not of diagnosis on verbal memory. Greater cortisol levels were related to poorer memory performance independent of group. In contrast, a significant interaction between cortisol and diagnosis was found for a color-word index of response inhibition. This interaction suggests that the detrimental effect of elevated cortisol level on this type of executive functioning exists only in the healthy control group but not in MDs. On an Interference score, another measure of response inhibition, cortisol had a significant independent effect, but neither the effects of diagnosis and the interaction attained full significance. Our study suggests that cortisol has an independent effect on verbal memory. Also, our study produced evidence of an interaction between diagnosis and cortisol on response inhibition.
View details for DOI 10.1016/j.psyneuen.2009.01.017
View details for Web of Science ID 000267471900008
View details for PubMedID 19261389
Hippocampal and amygdalar volumes in psychotic and nonpsychotic unipolar depression
AMERICAN JOURNAL OF PSYCHIATRY
2008; 165 (7): 872-880
The limbic system is thought to underlie dysfunctional affective and cognitive processes in individuals with depression. Neuroanatomical studies of subjects with depression have often examined hippocampal and amygdalar structures, since they are two key structures of the limbic system. Research has often but not always found reduced hippocampal volume in patients with major depression. The purpose of the present study was to examine differences in hippocampal and amygdalar volumes in patients with depression subtypes relative to healthy comparison subjects.Participants were 1) patients with major depression with psychosis, 2) patients with major depression without psychosis, and 3) healthy comparison subjects. To examine hippocampal and amygdalar volumes, all participants underwent structural magnetic resonance imaging (MRI). The authors further examined the effects of clinical and chronicity data on these two brain structures.After age, gender, and total brain volume were controlled, depressed patients with psychosis had a significantly smaller mean amygdala volume relative to depressed patients without psychosis and healthy comparison subjects. There were no differences between depressed patients without psychosis and healthy comparison subjects. Correlational analyses suggested that age of depression onset was strongly associated with amygdala volume. No group differences in hippocampal volume were found.There were no differences between depressed patients and healthy comparison subjects in hippocampal volume. However, psychotic but not nonpsychotic depression was associated with reduced amygdala volume. Reduced amygdala volume was not associated with severity of depression or severity of psychosis but was associated with age at onset of depression. Smaller amygdala volume may be a risk factor for later development of psychotic depression. In addition, chronicity of depression and depression subtype might be two important factors associated with hippocampal and amygdalar volumes in depression.
View details for DOI 10.1176/appi.ajp.2008.07081257
View details for Web of Science ID 000257320100016
View details for PubMedID 18450931
View details for PubMedCentralID PMC3733673
Efficacy of Duloxetine for the Treatment of Depression: Relationship to Most Recent Antidepressant Trial
2008; 41 (1): 34-45
To describe and examine, in a sample of depressed outpatients, the relationship between level of response to a previous SSRI or SNRI antidepressant trial and subsequent response to duloxetine hydrochloride.Data collected from a multicenter trial that evaluated the safety and efficacy of duloxetine for the treatment of major depressive disorder were analyzed to determine the relationship between response to previous antidepressant treatment and degree of response to duloxetine. Time to first response, first remission, sustained response, and sustained remission during the first 12 weeks of duloxetine treatment were compared across patient groups.Response and remission with duloxetine treatment ranged between 57 and 68% and 29 and 57%, respectively, and did not differ significantly across previous response levels. An additional analysis, collapsing the partial responder and responder without remission groups, indicated significantly lower rates of remission in those patients who demonstrated nonresponse to the most recent antidepressant treatment.Findings suggest that patient's response to duloxetine, when used as a switch treatment, may not be significant influenced by degree of response to the most recent antidepressant treatment.
View details for Web of Science ID 000207792400003
View details for PubMedID 18362869
Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness - A double-blind, placebo-controlled study
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
2007; 27 (6): 614-619
Previous studies suggest that adjunctive modafinil treatment provides benefit for patients with depression with significant sleepiness and fatigue.We conducted a multisite, double-blind, placebo-controlled study of the treatment of major depression characterized by excessive sleepiness and fatigue, adding adjunctive modafinil or placebo to a selective serotonin reuptake inhibitor from the beginning of treatment. Seventy-three of 90 consenting patients met all screening criteria to begin treatment with open-label selective serotonin reuptake inhibitor therapy and double-blind addition of either modafinil (100 mg/d for 1 week then 200 mg/d) or matching placebo for 6 weeks.Mixed-model analysis of the change in the Epworth Sleepiness Scale, the primary outcome measure, showed no difference between modafinil- and placebo-treated patients. However, the hypersomnia items on the 31-item Hamilton Depression Scale were significantly more improved with modafinil than placebo. The total 31-item Hamilton Depression Scale score was significantly better with modafinil than placebo at Weeks 4 and 5, but not at the final study visit. There was no difference in dropout rates caused by adverse events, but 2 patients in the modafinil-treated group developed new onset or worsening of suicidal ideation, leading to the trial being discontinued prematurely.Power to detect differences between modafinil and placebo was limited because of the premature discontinuation of the trial. Although modafinil did not show evidence of benefit over placebo on the Epworth Sleepiness Scale, secondary measures suggested modafinil may have provided benefit for symptoms of excessive sleepiness in patients with depression.
View details for DOI 10.1097/jcp.0b013e31815abefb
View details for Web of Science ID 000251181600010
View details for PubMedID 18004129
Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial
2007; 62 (11): 1208-1216
We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression.In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD.Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain.Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.
View details for DOI 10.1016/j.biopsych.2007.01.018
View details for Web of Science ID 000251119600003
View details for PubMedID 17573044
Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus
2007; 62 (5): 429-437
Positron emission tomography (PET) studies of major depression have revealed resting-state abnormalities in the prefrontal and cingulate cortices. Recently, fMRI has been adapted to examine connectivity within a specific resting-state neural network--the default-mode network--that includes medial prefrontal and anterior cingulate cortices. The goal of this study was to examine resting-state, default-mode network functional connectivity in subjects with major depression and in healthy controls.Twenty-eight subjects with major depression and 20 healthy controls underwent 5-min fMRI scans while resting quietly. Independent component analysis was used to isolate the default-mode network in each subject. Group maps of the default-mode network were compared. A within-group analysis was performed in the depressed group to explore effects of depression refractoriness on functional connectivity.Resting-state subgenual cingulate and thalamic functional connectivity with the default-mode network were significantly greater in the depressed subjects. Within the depressed group, the length of the current depressive episode correlated positively with functional connectivity in the subgenual cingulate.This is the first study to explore default-mode functional connectivity in major depression. The findings provide cross-modality confirmation of PET studies demonstrating increased thalamic and subgenual cingulate activity in major depression. Further, the within-subject connectivity analysis employed here brings these previously isolated regions of hypermetabolism into the context of a disordered neural network. The correlation between refractoriness and subgenual cingulate functional connectivity within the network suggests that a quantitative, resting-state fMRI measure could be used to guide therapy in individual subjects.
View details for DOI 10.1016/j.biopsych.2006.09.020
View details for Web of Science ID 000249042800009
View details for PubMedID 17210143
The neuropsychological profile of psychotic major depression and its relation to cortisol
2006; 60 (5): 472-478
Our study described the neuropsychological profile of psychotic major depression (PMD) compared to nonpsychotic major depression (NPMD) patients and psychiatrically healthy controls (HC). We predicted that higher cortisol levels would be associated with greater cognitive deficits.Twenty-nine PMDs, 24 NPMDs, and 26 HCs were recruited at Stanford University Medical Center. Psychiatric ratings, cortisol levels from 1800-0900 hours, and neuropsychological test data were obtained.PMDs had more severe cognitive impairments compared with NPMDs and HCs with the exception of simple verbal attention. PMDs had elevated mean cortisol levels from 1800 to 0100 hours which were significantly correlated with poorer verbal memory and psychomotor speed performance. Cortisol slopes from 1800 to 0100 hours were also significantly correlated with verbal memory and working memory.While PMDs' ability to attend passively to information appears intact, they have more difficulty processing, manipulating, and encoding new information. Elevated cortisol levels, as seen in PMD patients, are associated with poorer cognitive performance especially related to verbal memory for lists of words and working memory.
View details for DOI 10.1016/j.biopsych.2005.11.010
View details for Web of Science ID 000240506000007
View details for PubMedID 16483550
Cortisol circadian rhythm alterations in psychotic major depression
2006; 60 (3): 275-281
Increased hypothalamic-pituitary-adrenal axis activity is well described in psychotic depression with an emphasis on 24-hour, urinary free cortisol levels or dexamethasone suppression tests. There are limited data on cortisol levels during specific times of the day.Patients with depression with (PMD) and without (NPMD) psychosis and healthy control subjects were studied using rating scales of depression and psychosis and measures of HPA activity, including overnight cortisol and adrenocorticotropin levels. We used analysis of variance to determine group differences and regression analyses to assess contributions of specific measures to cortisol levels.PMDs had higher cortisol during the evening hours than did NPMDs or control subjects, who did not differ from one another. Regression analyses suggest that depression and the combination of depressive and psychotic symptoms were important contributors to variance in evening cortisol.PMD is associated with increased cortisol levels during the quiescent hours. Enhanced cortisol activity, particularly a higher nadir, was related to depression severity and the interaction of depressive and psychotic symptoms. This increase suggests a defect in the action of the circadian timing system and HPA axis, creating a hormonal milieu similarly seen in early Cushing's syndrome and potentially an (im)balance of mineralocorticoid and glucocorticoid receptor activity.
View details for DOI 10.1016/j.biopsych.2005.10.014
View details for Web of Science ID 000239543800009
View details for PubMedID 16458262
Clinical and biological effects of mifepristone treatment for psychotic depression
2006; 31 (3): 628-636
Psychotic major depression (PMD) is found to be a relatively common psychiatric condition that affects up to nearly 20% of patients with major depression. Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone, in addition to restoring a more normal afternoon cortisol release. The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed. In total, 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a randomized double-blind manner. The Hamilton Depression Rating Scale (HDRS) and the Brief Psychiatric Rating Scale (BPRS) were administered at baseline and again after 8 days of treatment. Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment. Significantly, more patients in the mifepristone group (seven of 15) showed a 50% or greater decline on the BPRS positive symptom subscale, an index of psychotic symptoms, as compared to the placebo group (two of 15). Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo, but these differences were not statistically significant. In addition, mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo. Clinical and biological effects of mifepristone were comparable among males and females. Age was found to significantly and positively correlate with changes in cortisol and ACTH. These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis. Additional blinded studies are warranted.
View details for DOI 10.1038/sj.npp.1300884
View details for Web of Science ID 000236141600015
View details for PubMedID 16160710
A placebo-controlled, randomized, double-blind study of adjunctive bupropion sustained release in the treatment of SSRI-induced sexual dysfunction
JOURNAL OF CLINICAL PSYCHIATRY
2005; 66 (7): 844-848
Sexual side effects are among the common reasons patients discontinue selective serotonin reuptake inhibitors (SSRIs). While many antidotes have been proposed, few have been subjected to double-blind trials. Some evidence has suggested that bupropion may be an effective antidote for SSRI-induced sexual dysfunction. In this double-blind trial, the efficacy of a standard dose of bupropion sustained release (SR) is evaluated in the treatment of SSRI-induced sexual dysfunction.Patients with a history of SSRI-induced sexual side effects were randomly assigned to adjunctive treatment with either bupropion SR 150 mg daily or placebo for 6 weeks. Assessments of sexual function and interest included the Arizona Sexual Experiences Scale (ASEX), Brief Index of Sexual Functioning, and a 10-point visual analogue scale. Efficacy was defined as a 50% improvement on the ASEX at the end of 6 weeks. Data were collected from January 1999 to March 2001.Forty-one patients entered the study and completed the 6-week trial. No significant differences were seen between placebo and bupropion SR on the ASEX or on any measure of sexual functioning at the end of the trial.A fixed dose of 150 mg/day of bupropion SR taken in the morning does not appear to be effective in the treatment of SSRI-induced sexual dysfunction. Additional trials will be required to define what role, if any, bupropion might have in the treatment of SSRI-induced sexual side effects.
View details for Web of Science ID 000230663800006
View details for PubMedID 16013899
A prospective trial of modafinil as an adjunctive treatment of major depression
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
2004; 24 (1): 87-90
Modafinil is a wake-promoting agent approved by the Federal Drug Administration for the treatment of narcolepsy. Preliminary evidence indicates that modafinil may improve fatigue and excessive sleepiness associated with a variety of conditions. The purpose of this study was to investigate the utility of modafinil as an adjunctive treatment of depressed patients. Subjects with a history of major depression with partial response on a stable therapeutic dose of an antidepressant were eligible to participate. All subjects endorsed complaints of significant fatigue and/or excessive sleepiness on clinical assessment. Modafinil was added to their existing regimen at a dose of 100 to 400 mg/d for 4 weeks. Subjects were assessed at 2-week intervals for improvement using the standard depression scales (HDRS, BDI, CGI), fatigue scales (VASF, FSI), and a neuropsychologic battery. Thirty-five subjects were entered and 31 subjects completed the 4-week trial. Significant improvements were seen across all 3 measures of depression (HDRS, BDI, CGIS) and both measures of fatigue (VASF, FSI). On the neurocognitive battery, significant gains in the Stroop Interference Test were seen at 4 weeks, whereas the other cognitive tests showed no change. Modafinil may be a useful and a well-tolerated adjunctive agent to standard antidepressants in the treatment of major depression.
View details for DOI 10.1097/01.jcp.0000104910.75206.b9
View details for Web of Science ID 000188093400015
View details for PubMedID 14709953
Predictors of response in anxiety disorders
PSYCHIATRIC CLINICS OF NORTH AMERICA
2003; 26 (2): 411-?
Anxiety disorder variables such as duration, severity of illness, and comorbidity with other anxiety or mood disorders appear to identify individuals who are at the greatest risk of treatment nonresponse. Conversely, in accord with clinical experience, shorter periods of illness, less severe illness, being treatment naive, and the absence of comorbidity tend to identify patients who are likely to respond robustly to medication management. Symptom clusters in OCD and PTSD are promising as a means of stratifying those more likely to respond to standard pharmacologic treatment. The presence of hoarding or sexual obsessions seems to presage poorer response in OCD, while the presence of dissociative symptoms in PTSD has been linked to high nonspecific treatment response rates to placebo. Genotyping individuals with respect to genes that are thought to have an important role in the underlying disease process, such as the work with the 5HTTL-PR allele, is exciting and is perhaps the first glimmer of using genotyping to identify treatment strategies or to predict the likelihood or speed of response. The use of neuroimaging as a means of identifying individuals who may respond favorably to pharmacologic or neurosurgical intervention is still in its infancy. As a strategy, it may help combine symptom severity and response variables into a clear neurobiologic vulnerability model of illness. In the future, it may be possible to identify specific treatment interventions for specific patterns of abnormal metabolic rates in certain areas of the brain. However, it should be emphasized that such an approach has not been empirically demonstrated in a rigorous experimental context at this time.
View details for DOI 10.1016/S0193-953X(03)00027-3
View details for Web of Science ID 000182929300008
View details for PubMedID 12778841
A prospective trial of bupropion SR augmentation of partial and non-responders to Serotonergic antidepressants
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
2003; 23 (1): 27-30
Many patients fail to achieve an adequate response to a given antidepressant trial. The best-studied augmentation agents, lithium and thyroid supplementation are less commonly used. Augmenting antidepressants with bupropion has become an increasingly common strategy in the treatment of resistant depression. Several case reports and 2 open label studies suggest efficacy of this strategy. The purpose of this study is to further examine the utility of bupropion sustained release (SR) augmentation in patients with inadequate response to selective serotonin reuptake inhibitors. Patients who met DSM-IV criteria for major depression and had failed to achieve adequate response to an SSRI were considered for this study. Eligible patients were required to have a score of 16 on the 24-item Hamilton Depression Rating Scale (HDRS). Patients were treated openly for 6 weeks with bupropion SR added to their existing antidepressant. The dose range of bupropion was 150 to 300 mg per day. At each visit, patients were assessed using the Beck Depression Inventory (BDI), the Hamilton Depression Ratings Scale (HDRS), and the Clinical Global Impression (CGI). Twenty-eight patients (12 men, 16 women) entered the study. Twenty-five patients completed the six-week trial. With respect to the clinical benefit of bupropion SR augmentation, 15 out of 28, or 54% of patients, were classified as responders, showing a decrease in their HDRS or BDI scores of 50% or more between baseline and Week 6. This prospective, open-label trial supports the use of bupropion SR in the augmentation of SSRIs and venlafaxine. Placebo controlled trials should be completed to further evaluate the efficacy of this strategy.
View details for Web of Science ID 000180765000005
View details for PubMedID 12544372
- Psychological versus biological clinical interpretation: A patient with prion disease AMERICAN JOURNAL OF PSYCHIATRY 2002; 159 (4): 528-537
Case report: Limbic system activation by intravenous lidocaine in a patient with a complex regional pain syndrome and major depression
2000; 1 (4): 358-361
Intravenous lidocaine is used to treat various neuropathic pain states. Systemic local anesthetics have been reported to cause behavioral alteration via limbic system activation. This case report describes a dramatic behavioral change in a patient receiving intravenous lidocaine and suggests a possible use of lidocaine to discriminate somatic and affective pain characteristics.
View details for Web of Science ID 000168278700012
View details for PubMedID 15101882
- Agranulocytosis associated with lamotrigine AMERICAN JOURNAL OF PSYCHIATRY 2000; 157 (10): 1704-1704
- Pramipexole augmentation of a selective serotonin reuptake inhibitor in the treatment of depression JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY 2000; 20 (2): 274-275
Psychoneuroendocrine immunology: Perception of stress can alter body temperature and natural killer cell activity
INTERNATIONAL JOURNAL OF NEUROSCIENCE
1999; 98 (1-2): 95-129
Psychoimmunology has been credited with using the mind as a way to alter immunity. The problem with this concept is that many of the current psychoimmunology techniques in use are aimed at alleviating stress effects on the immune system rather than at direct augmentation of immunity by the brain. Studies in animals provide a model that permits us to approach the difficulties associated with gaining an understanding of the CNS-immune system connection. A particular advantage of using animals over humans is that psychological and social contributions play a less prominent role for animals than for human subjects, since the animals are all inbred and reared under identical controlled conditions. If the insightful information provided by animal studies is correct, then psychotherapy for the treatment of diseases might be made more effective if some aspect of this knowledge is included in the design of the treatment. We emphasize conditioning as a regimen and an acceptable way to train the brain to remember an output pathway to raise immunity. We propose that a specific drug or perception (mild stress, represented by rotation, total body heating or handling) could substitute and kindle the same output pathway without the need for conditioning. If this view is correct, then instead of using conditioning, it may be possible to use an antigen to activate desired immune cells, and substitute a drug or an external environmental sensory stimulus (perception) to energize the output pathway to these cells. Alternatively, monitoring alterations of body temperature in response to a drug or perception might allow us to follow how effectively the brain is performing in altering immunity. Studies with animals suggest that there are alternative ways to use the mind to raise natural or acquired immunity in man.
View details for Web of Science ID 000081029200005
View details for PubMedID 10395364
ECT in dissociative identity disorder and comorbid depression
JOURNAL OF ECT
1998; 14 (4): 275-279
Dissociative identity disorder (DID), previously named multiple personality disorder, is a diagnosis often complicated by comorbid major depression. We report on four cases of DID associated with severe self-destructive behavior and comorbid major depression treated with electroconvulsive therapy (ECT). In three of the patients, ECT appeared to be helpful in treating the comorbid depression without adversely affecting the DID. The potential risks of using ECT in patients with DID are reviewed.
View details for Web of Science ID 000084422900011
View details for PubMedID 9871851
- Treatment of psychotic depression AMERICAN JOURNAL OF PSYCHIATRY 1997; 154 (11): 1625-1626
- A 25-year-old woman with hallucinations, hypersexuality, nightmares, and a rash AMERICAN JOURNAL OF PSYCHIATRY 1996; 153 (4): 545-551
THE IDENTITY OF THE UNCONDITIONED STIMULUS TO THE CENTRAL-NERVOUS-SYSTEM IS INTERFERON-BETA
JOURNAL OF NEUROIMMUNOLOGY
1993; 45 (1-2): 75-81
The specific mechanism of interaction between the central nervous system and immune system was examined using conditioned augmentation of natural killer (NK) cell activity. This study focused on the role of interferon-beta (IFN-beta) as the unconditioned stimulus (US). IFN-beta was found to be the signal responsible for the bidirectional communication which links the central nervous system with the immune system. This was substantiated by injection of small quantities of IFN-beta directly into the cisterna magna, which activated the effector pathway from the central nervous system to the immune system. More importantly, we found that when the conditioned stimulus (CS) was paired with an injection of IFN-beta into the cisterna magna, the conditioned animals were able to raise their natural killer cell activity in response to subsequent exposure to the conditioned stimulus. These studies show the unconditioned response must be the response of the central nervous system (CNS) to the unconditioned stimulus and not the direct effect of the substance injected into the periphery.
View details for Web of Science ID A1993LL51700010
View details for PubMedID 8331167
A SIMPLE, SINGLE, TRIAL-LEARNING PARADIGM FOR CONDITIONED INCREASE IN NATURAL-KILLER-CELL ACTIVITY
PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE
1992; 199 (2): 199-203
A change in natural killer (NK) cell activity can be conditioned with one trial learning when conditioned stimulus (CS) precedes the unconditioned stimulus (US). To avoid the problems associated with two reexposures in our earlier studies, we have developed a reliable and simple conditioning protocol utilizing the one trial learning and one reexposure to the odor CS. The conditioned change in NK cell activity was significantly different (P less than 0.05) from the control groups of mice. The paradigm is short and simple in that the conditioned change could be demonstrated within 3 days. We have also compared the effects of temporal association of CS and US on conditioned increase in NK cell activity. Forward conditioning (CS preceded the US) demonstrated a conditioned change, but the backward conditioning protocol did not. The paradigm provides a reliable approach to the study of mechanisms of the phenomenon of odor-NK conditioning.
View details for Web of Science ID A1992HA55800009
View details for PubMedID 1741412
MEASUREMENT OF THE THERMAL-DIFFUSIVITY OF HUMAN EPIDERMIS BY STUDYING THERMAL WAVE-PROPAGATION
PHYSICS IN MEDICINE AND BIOLOGY
1992; 37 (1): 21-35
The thermal diffusivity of dry human epidermis was determined in vitro by studying thermal wave propagation in thin epidermal layers at frequencies between 10 and 200 Hz. Transmission measurements were performed on samples applied to a plane copper support at the underside of which thermal waves were generated by means of a square voltage controlled power transistor. Additionally, measurements were performed on epidermal layers with metal and air backing, in which thermal waves were generated by the absorption of intensity modulated light in a thin, superficially applied graphite layer (short and open circuit measurements). Thermal waves were detected by means of the laser beam deflection technique which allows the contactless measurement of the oscillatory surface temperature of a sample with respect to amplitude and phase. A critical discussion of methods shows that the thermal diffusivity is most reliably determined by transmission experiments. From experimental data obtained by this method a mean value alpha = (2.8 +/- 0.9) x 10(-4) cm2 s-1 was evaluated for the thermal diffusivity of dry epidermis.
View details for Web of Science ID A1992GZ82400002
View details for PubMedID 1741425
A BEHAVIORAL AUGMENTATION OF NATURAL IMMUNITY - ODOR SPECIFICITY SUPPORTS A PAVLOVIAN CONDITIONING MODEL
INTERNATIONAL JOURNAL OF NEUROSCIENCE
1991; 61 (3-4): 277-288
BALB/c mice were conditioned by pairing an odor to an injection of poly-inosinic:poly-cytidylic acid (poly I:C), a strong inducer of natural killer (NK) cell activity as the unconditioned stimulus (US). When later reexposed to the odor conditioning stimulus (CS), these mice showed a conditioned augmentation of the NK cell response to a suboptimal dose of 1 microgram poly I:C. The two stimuli used in these studies were camphor (Ca) and citronella oil (Cr) odors, two chemically-related but distinct odor stimuli. The conditioned mice demonstrated the ability to discriminate between Ca and Cr, such that the conditioned response (CR) was only elicited by the odor CS used in the formation of the conditioned association. Exposure of conditioned mice to the non-associated odor stimulus on the test day did not elicit a change in the NK cell response to the suboptimal dose of poly I:C when compared to mice in the US group that had been given the US on day 0 without pairing to either odor stimulus. This specificity of the CR for the odor CS and not the unassociated odor stimulus supports the interpretation that the elevation of NK cell activity in this paradigm is due to Pavlovian conditioning and therefore dependent on central nervous system (CNS) associative processes.
View details for Web of Science ID A1991HC43600010
View details for PubMedID 1824390
CONDITIONING - A NEW APPROACH TO IMMUNOTHERAPY
1990; 50 (14): 4295-4299
It has been demonstrated by Parmiani et al. (Int. J. Cancer, 29: 323-332, 1982) that a significant protective effect can be obtained against the transplanted syngeneic YC8 lymphoma by prior immunization of BALB/c mice with normal allogeneic DBA/2 spleen cells. Using this well established tumor model, we investigated a novel approach, conditioning of specific immunotherapeutic activity. For this purpose, we used the odor of camphor as the conditioning stimulus and allogeneic DBA/2 spleen cells as unconditioning stimulus. We associated the conditioning and unconditioning stimuli two, three, and four times. Following this the conditioned animals were reexposed to the odor of camphor only. In each case, we observed a delay in tumor growth and in some instances the conditioned group performed better than the immunotherapy control group. These results indicate that a limited number of treatments with the antigen is better than the continuous treatment in maintaining the immunity and the homeostasis of the system.
View details for Web of Science ID A1990DM71800021
View details for PubMedID 2364386
CONDITIONED AUGMENTATION OF NATURAL-KILLER CELL-ACTIVITY - INDEPENDENCE FROM NOCICEPTIVE EFFECTS AND DEPENDENCE ON INTERFERON-BETA
JOURNAL OF IMMUNOLOGY
1988; 140 (2): 661-665
Injection of mice with 20 micrograms polyinosinic: polycytidylic acid (Poly I:C) after exposure to camphor odor results in a conditioned augmentation of natural killer cell (NK) activity. In this study, we show that the conditioned response is not the result of nociceptive stimulation and that interferon-beta (IFN), but not IFN-alpha can replace Poly I:C as the unconditioned stimulus (US). Two conditioned stimuli (CS) were used with equivalent results. A combination CS consisting of a novel taste (saccharin) and a 125 mg/kg injection of LiCl that induces gastric upset was paired with a Poly I:C or IFN-beta (1 X 10(4) IU) injection. This resulted in an augmentation of NK activity when the conditioned animals were reexposed to the saccharin-LiCl CS. In addition, an identical conditioned response was elicited when a camphor odor CS was paired with either of these US. To test whether the conditioned response might be an artifact not detected by our controls, a mock conditioning experiment was performed, which assessed the differential effect of multiple exposures to the saccharin-LiCl CS without a CS/US pairing. The mock conditioned group was significantly suppressed relative to saline treated controls, whereas the mock nonconditioned group and the mock conditioned group that was not reexposed to the CS after conditioning did not show significant suppression. This indicates that the augmentation observed in the conditioned group after CS/US pairing was not the result of exposure to the CS itself. Small doses of Poly I:C (5 micrograms or 2.5 micrograms) given on days 3 and 5 (or on day 5 only) to boost NK activity had the effect of increasing the magnitude of the conditioned response measured on day 6. In addition, an identical conditioned response was observed when the interval between the CS/US pairing and the later CS exposures was changed, which places the test for the conditioned response either on day 6 (CS given on days 3 and 5) or day 10 (CS given on days 7 and 9). These results show that the observed conditioned enhancement of NK activity in conditioned animals is not caused by any nociceptive properties of the CS itself and is dependent on the IFN-beta produced after Poly I:C injection in the conditioned paradigm.
View details for Web of Science ID A1988L772500049
View details for PubMedID 2826599