Anna Lembke, MD

All Publications

• The opioid industry's use of scientific evidence to advance claims about prescription opioid safety and effectiveness. Health affairs scholar Gupta, R., Chernesky, J., Lembke, A., Michaels, D., Tomori, C., Greene, J. A., Alexander, G. C., Koon, A. D. 2024; 2 (10): qxae119

  Abstract

  It is widely recognized that pharmaceutical marketing contributed to the ongoing US opioid epidemic, but less is understood about how the opioid industry used scientific evidence to generate product demand, shape opioid regulation, and change clinician behavior. In this qualitative study, we characterize select scientific articles used by industry to support safety and effectiveness claims and use a novel database, the Opioid Industry Documents Archive, to determine notable elements of industry and non-industry documents citing the scientific articles to advance each claim. We found that 15 scientific articles were collectively mentioned in 3666 documents supporting 5 common, inaccurate claims: opioids are effective for treatment of chronic, non-cancer pain; opioids are "rarely" addictive; "pseudo-addiction" is due to inadequate pain management; no opioid dose is too high; and screening tools can identify those at risk of developing addiction. The articles contributed to the eventual normalization of these claims by symbolically associating the claims with scientific evidence, building credibility, expanding and diversifying audiences and the parties asserting the claims, and obfuscating conflicts of interest. These findings have implications for regulators of industry products and corporate activity and can inform efforts to prevent similar public health crises.

  View details for DOI 10.1093/haschl/qxae119

  View details for PubMedID 39450313

  View details for PubMedCentralID PMC11500661

• Trends in hallucinogen-associated emergency department visits and hospitalizations in California, USA, from 2016 to 2022. Addiction (Abingdon, England) Garel, N., Tate, S., Nash, K., Lembke, A. 2024

  Abstract

  Hallucinogens encompass a diverse range of compounds of increasing scientific and public interest. Risks associated with hallucinogen use are under-researched and poorly understood. We aimed to compare the trends in hallucinogen-associated health-care use with alcohol- and cannabis-associated health-care use.We conducted an ecological study with publicly available data on International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes associated with emergency department (ED) visits and hospitalizations from the California Department of Healthcare Access and Information (HCAI). HCAI includes primary and secondary ICD-10 codes reported with ED or hospital discharge from every non-federal health-care facility licensed in California, United States, from 2016 to 2022.ICD-10 codes were classified as hallucinogen-, cannabis- or alcohol-associated if they were from the corresponding category in the ICD-10 block 'mental and behavioral disorders due to psychoactive substance use'.Observed hallucinogen-associated ED visits increased by 54% between 2016 and 2022, from 2260 visits to 3476 visits, compared with a 20% decrease in alcohol-associated ED visits and a 15% increase in cannabis-associated ED visits. The observed hallucinogen-associated hospitalizations increased by 55% during the same period, from 2556 to 3965 hospitalizations, compared with a 1% increase in alcohol-associated hospitalizations and a 1% increase in cannabis-associated hospitalizations. This rise in hallucinogenic ED visits was significantly different from the trend in cannabis-associated (P < 0.001) and alcohol-associated (P = 0.005) ED visits. The hallucinogen-associated hospitalizations trend also significantly differed when compared with cannabis- (P < 0.001) and alcohol-associated (P < 0.001) hospitalizations.Hallucinogen-associated emergency department visits and hospitalizations in California, USA, showed a large relative but small absolute increase between 2016 and 2022.

  View details for DOI 10.1111/add.16432

  View details for PubMedID 38213013

• Responding to the opioid crisis in North America and beyond: recommendations of the Stanford-Lancet Commission. Lancet (London, England) Humphreys, K., Shover, C. L., Andrews, C. M., Bohnert, A. S., Brandeau, M. L., Caulkins, J. P., Chen, J. H., Cuellar, M., Hurd, Y. L., Juurlink, D. N., Koh, H. K., Krebs, E. E., Lembke, A., Mackey, S. C., Larrimore Ouellette, L., Suffoletto, B., Timko, C. 2022; 399 (10324): 555-604

  View details for DOI 10.1016/S0140-6736(21)02252-2

  View details for PubMedID 35122753

• Dopamine Nation: Finding Balance in the Age of Indulgence Lembke, A. Dutton Penguin Random House. 2021
• Drug Dealer, MD: How Doctors Were Duped, Patients Got Hooked, and Why It’s So Hard to Stop Lembke, A. Johns Hopkins University Press. 2016
• Predictability of buprenorphine-naloxone treatment retention: A multi-site analysis combining electronic health records and machine learning. Addiction (Abingdon, England) Nateghi Haredasht, F., Fouladvand, S., Tate, S., Chan, M. M., Yeow, J. J., Griffiths, K., Lopez, I., Bertz, J. W., Miner, A. S., Hernandez-Boussard, T., Chen, C. A., Deng, H., Humphreys, K., Lembke, A., Vance, L. A., Chen, J. H. 2024

  Abstract

  Opioid use disorder (OUD) and opioid dependence lead to significant morbidity and mortality, yet treatment retention, crucial for the effectiveness of medications like buprenorphine-naloxone, remains unpredictable. Our objective was to determine the predictability of 6-month retention in buprenorphine-naloxone treatment using electronic health record (EHR) data from diverse clinical settings and to identify key predictors.This retrospective observational study developed and validated machine learning-based clinical risk prediction models using EHR data.Data were sourced from Stanford University's healthcare system and Holmusk's NeuroBlu database, reflecting a wide range of healthcare settings. The study analyzed 1800 Stanford and 7957 NeuroBlu treatment encounters from 2008 to 2023 and from 2003 to 2023, respectively.Predict continuous prescription of buprenorphine-naloxone for at least 6 months, without a gap of more than 30 days. The performance of machine learning prediction models was assessed by area under receiver operating characteristic (ROC-AUC) analysis as well as precision, recall and calibration. To further validate our approach's clinical applicability, we conducted two secondary analyses: a time-to-event analysis on a single site to estimate the duration of buprenorphine-naloxone treatment continuity evaluated by the C-index and a comparative evaluation against predictions made by three human clinical experts.Attrition rates at 6 months were 58% (NeuroBlu) and 61% (Stanford). Prediction models trained and internally validated on NeuroBlu data achieved ROC-AUCs up to 75.8 (95% confidence interval [CI] = 73.6-78.0). Addiction medicine specialists' predictions show a ROC-AUC of 67.8 (95% CI = 50.4-85.2). Time-to-event analysis on Stanford data indicated a median treatment retention time of 65 days, with random survival forest model achieving an average C-index of 65.9. The top predictor of treatment retention identified included the diagnosis of opioid dependence.US patients with opioid use disorder or opioid dependence treated with buprenorphine-naloxone prescriptions appear to have a high (∼60%) treatment attrition by 6 months. Machine learning models trained on diverse electronic health record datasets appear to be able to predict treatment continuity with accuracy comparable to that of clinical experts.

  View details for DOI 10.1111/add.16587

  View details for PubMedID 38923168

• Predicting premature discontinuation of medication for opioid use disorder from electronic medical records. AMIA ... Annual Symposium proceedings. AMIA Symposium Lopez, I., Fouladvand, S., Kollins, S., Chen, C. A., Bertz, J., Hernandez-Boussard, T., Lembke, A., Humphreys, K., Miner, A. S., Chen, J. H. 2023; 2023: 1067-1076

  Abstract

  Medications such as buprenorphine-naloxone are among the most effective treatments for opioid use disorder, but limited retention in treatment limits long-term outcomes. In this study, we assess the feasibility of a machine learning model to predict retention vs. attrition in medication for opioid use disorder (MOUD) treatment using electronic medical record data including concepts extracted from clinical notes. A logistic regression classifier was trained on 374 MOUD treatments with 68% resulting in potential attrition. On a held-out test set of 157 events, the full model achieved an area under the receiver operating characteristic curve (AUROC) of 0.77 (95% CI: 0.64-0.90) and AUROC of 0.74 (95% CI: 0.62-0.87) with a limited model using only structured EMR data. Risk prediction for opioid MOUD retention vs. attrition is feasible given electronic medical record data, even without necessarily incorporating concepts extracted from clinical notes.

  View details for PubMedID 38222349

  View details for PubMedCentralID PMC10785878

• Qualitative exploration of the psychological dimensions of telehealth shared medical appointments (SMAs) for buprenorphine prescribing. Journal of addictive diseases Greenberg, B., C, A., Lucitt, L., Haug, N. A., Lembke, A. 2022: 1-10

  Abstract

  Background: Shared medical appointments (SMAs) for buprenorphine prescribing are clinical encounters in which multiple patients with opioid problems receive treatment from providers in a group setting. Telehealth, the provision of clinical services remotely using telecommunications technology, is an essential modality for improving access to healthcare when combined with SMAs, especially since the COVID pandemic. Objectives: The current study specifically examined psychological components of telehealth SMAs for buprenorphine prescribing to learn about the benefits and drawbacks of this treatment model. Methods: Data was collected through qualitative interviews with patients (N=10) in a psychiatry addiction medicine clinic. Narrative synthesis using grounded theory was conducted to identify salient themes from the interviews. Results: Findings highlighted the advantages and downsides of telehealth SMA to treat addictive disorders in a digital age: (1) Shared group identity; (2) Decreased stigma around buprenorphine; (3) Benefits of telehealth; (4) Discomfort with group SMA format; (5) Strategies for managing medication side effects; and (6) Enhanced empathy for providers. Several themes corresponded to therapeutic factors identified in group therapy (i.e., installation of hope, universality, imparting information, altruism) and mechanisms theorized in previous SMA research (e.g., combating isolation, disease self-management, feeling inspired by others). Conclusion: Telehealth SMAs for buprenorphine prescribing may be a unique opportunity for patients to receive both ongoing medication management and psychosocial benefits that promote recovery and reduce stigma. The SMA group had shortcomings for some patients, including privacy concerns, fear of judgment from other patients and limited time to discuss individual concerns with providers.

  View details for DOI 10.1080/10550887.2022.2123669

  View details for PubMedID 36374272

• A telehealth inpatient addiction consult service is both feasible and effective in reducing readmission rates. Journal of addictive diseases Deng, H., Raheemullah, A., Fenno, L. E., Lembke, A. 2022: 1-8

  Abstract

  The COVID-19 pandemic compelled fast adaptation of telehealth to addiction treatment services. This study aims to examine the feasibility and effectiveness of transitioning an in-person hospital addiction consult service (ACS) to telehealth. The Stanford Hospital ACS adapted to the pandemic by transforming an in-person ACS to a telehealth ACS. We compared 30-day readmission rates in patients with and without an addiction medicine consult pre-pandemic (in-person ACS) and during the pandemic (telehealth ACS). The ACS completed 370 and 473 unique patient consults in the year preceding (in-person consults) and during the pandemic (telehealth consults) respectively. Patients seen by telehealth ACS had decreased 30-day readmission rates consistent with those seen before COVID-19. A telehealth ACS is feasible and effective in the in-patient setting. Telehealth ACS holds promise to extend the reach of substance use disorder evaluation and treatment in underserved areas.

  View details for DOI 10.1080/10550887.2022.2090822

  View details for PubMedID 35819268

• Buprenorphine Microdosing Cross Tapers: A Time for Change International Journal of Environmental Research and Public Health Raheemullah, A., Benhamou, O., Kuo, J., Lembke, A. 2022; 19 (24): 16436

  View details for DOI 10.3390/ijerph192416436

• Buprenorphine Induction Without Opioid Withdrawal: A Case Series of 15 Opioid-Dependent Inpatients Induced on Buprenorphine Using Microdoses of Transdermal Buprenorphine AMERICAN JOURNAL OF THERAPEUTICS Raheemullah, A., Lembke, A. 2021; 28 (4): E504-E508

  View details for Web of Science ID 000681356600019

• Gabapentin dependence and withdrawal requiring an 18-month taper in a patient with alcohol use disorder: a case report. Journal of addictive diseases Deng, H., Benhamou, O., Lembke, A. 2021: 1–6

  Abstract

  Gabapentin has been widely used to manage post-herpetic neuralgia, peripheral neuropathy, seizure disorders, alcohol use disorder (AUD), alcohol withdrawal, and insomnia. Although usually well tolerated, gabapentin has been reported to cause severe physiologic dependence and withdrawal. Tapering gabapentin in this context poses a significant clinical challenge, with little published information to date on meeting this challenge. This case highlights the need for patient-centered slow tapers in patients with severe gabapentin dependence and withdrawal. We present a 32-year-old female effectively treated for AUD with 1,200mg daily dose of gabapentin, who developed gabapentin dependence and severe withdrawal. Recognizing her intolerance to gabapentin withdrawal after a brief accidental pause of medication, a taper plan was initiated using the framework of the BRAVO Protocol. On average, she reduced daily gabapentin dose by 100mg per month until she reached 300mg. The taper then slowed to 20-30mg dose decrements per month. For the last 100mg, she tapered down at 5mg decrements every one to two weeks to 60mg, at which point she discontinued gabapentin. The entire taper process took eighteen months. The BRAVO protocol outlines a safe and compassionate strategy. Originally developed for opioids and adapted to benzodiazepines, the use of the Bravo Protocol provides a framework for a gabapentin taper. For patients in whom gabapentin treatment leads to severe dependence and withdrawal, the BRAVO Protocol provides a practical, patient-centered framework for tapering.

  View details for DOI 10.1080/10550887.2021.1907502

  View details for PubMedID 33783336

• A systematic review of stigma interventions for providers who treat patients with substance use disorders. Journal of substance abuse treatment Bielenberg, J., Swisher, G., Lembke, A., Haug, N. A. 2021; 131: 108486

  Abstract

  Stigma surrounding substance use disorders (SUDs) is a frequently cited barrier to treatment engagement. Research consistently demonstrates that healthcare professionals' attitudes towards patients with addiction problems are often negative and may adversely impact service delivery. The current study presents a systematic review of stigma interventions for providers who treat patients with SUDs, in order to evaluate the quality of existing studies and potential for implementation in clinical settings.This systematic literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases included PubMed, APA PsycInfo and the Cochrane Database of Systematic Reviews. Of the 1462 records identified between 2011 and 2019, 15 studies were eligible for inclusion. A narrative synthesis of stigma interventions summarized the change in stigmatizing attitudes held by providers.Studies included heterogeneous and culturally diverse samples of providers (N = 1324), who varied by age, location, discipline, and experience, with the exception of primarily female providers (75%). Results delineated six types of provider stigma interventions with components including online education, in-person education, in-person contact with consumers in recovery, or some combination of these elements. The highest quality studies incorporated motivational interviewing or communication training interventions, and many interventions combined either in-person mentorship or contact with individuals in recovery. Positive effects on provider attitudes occurred at several levels of educational and consumer contact interventions. Interventions with consumer contact demonstrated long-term maintenance of attitudinal shifts. Despite significant methodological limitations and low-quality assessment ratings, several studies utilized real-world providers and patients, as well as practical, innovative, brief, and potentially cost-effective interventions, particularly in locations with limited technological resources.Research on provider stigma interventions increased in recent years, indicating greater worldwide attention to the negative impact of stigma. While educational interventions alone can be helpful in attitudinal change, contact with individuals in recovery from SUDs is a vital component of provider stigma interventions, particularly for lasting effects. This review highlights the importance of including implementation outcomes, such as sustainability and cost-effectiveness, in the study of stigma interventions for providers of addiction treatment.

  View details for DOI 10.1016/j.jsat.2021.108486

  View details for PubMedID 34217033

• Unsafe Supply: Why Making Controlled Prescription Drugs Available for Unsupervised Use Will Not Target the Syndemic of HIV, Hepatitis C, Overdose, and COVID-19-A Commentary on Bonn et al. (2020) JOURNAL OF STUDIES ON ALCOHOL AND DRUGS Lembke, A. 2020; 81 (5): 564–65

  View details for Web of Science ID 000600600000006

• Online mutual-help intervention for reducing heavy alcohol use. Journal of addictive diseases Haug, N. A., Morimoto, E. E., Lembke, A. 2020: 1–9

  Abstract

  Online interventions have potential to reach a wide range of people, including heavy drinkers unable or unwilling to seek formal treatment or support groups. This study examined a self-guided alcohol Internet intervention that provides access to several different online social networks and is based on principles of harm reduction, cognitive-behavioral therapy (CBT), and relapse prevention. Active participants in the online program (N=57) completed a survey that retrospectively assessed prior alcohol use, current alcohol use patterns, drinking goals, involvement in online activities, and use of CBT self-help tools. Findings indicated significant reductions in drinks per week (DPW), drinks per day (DPD), and drinking days per week (DDW) from baseline to post-intervention. Longer time in the online program was associated with greater reduction in DDW, rs(57) = .31, p = .02; while use of CBT self-help tools was positively correlated with reduction in DPW, rs(57) = .37, p = .005. Engagement in multiple online activities (i.e., social networking, e-mail groups, chat room, forum discussion) was associated with greater drinking reductions in DPW, (F[1,55]) = 8.55, p < .005; and DDW, (F[1,55]) = 7.12, p < .01). Results suggest that an online program may assist heavy drinkers in decreasing alcohol use through utilization of a cyber community, social networking, and self-help tools. Conversely, 74% of participants were still engaging in high-risk drinking, raising the possibility that an online mutual-help group with personalized goals intended to reduce harm, may inadvertently normalize heavy alcohol use.

  View details for DOI 10.1080/10550887.2020.1747331

  View details for PubMedID 32314667

• Buprenorphine for Long-Term Chronic Pain Management: Still Looking for the Evidence ANNALS OF INTERNAL MEDICINE Chou, R., Ballantyne, J., Lembke, A. 2020; 172 (4): 294

  View details for Web of Science ID 000516744600036

• Buprenorphine for Long-Term Chronic Pain Management: Still Looking for the Evidence. Annals of internal medicine Chou, R., Ballantyne, J., Lembke, A. 2020; 172 (4): 294

  View details for DOI 10.7326/L19-0684

  View details for PubMedID 32066158

• Tapering Long-Term Opioid Therapy. American family physician Lembke, A. 2020; 101 (1): 49–52

  View details for PubMedID 31894939

• Unsafe Supply: Why Making Controlled Prescription Drugs Available for Unsupervised Use Will Not Target the Syndemic of HIV, Hepatitis C, Overdose, and COVID-19-- A Commentary on Bonn et al. (2020). Journal of studies on alcohol and drugs Lembke, A. n. 2020; 81 (5): 564–65

  View details for PubMedID 33028468

• Tapering Long-Term Opioid Therapy AMERICAN FAMILY PHYSICIAN Lembke, A. 2020; 101 (1): 49–52

  View details for Web of Science ID 000505644100017

• Patterns of Opioid and Benzodiazepine Use in Opioid-Naive Patients with Newly Diagnosed Low Back and Lower Extremity Pain. Journal of general internal medicine Azad, T. D., Zhang, Y., Stienen, M. N., Vail, D., Bentley, J. P., Ho, A. L., Fatemi, P., Herrick, D., Kim, L. H., Feng, A., Varshneya, K., Jin, M., Veeravagu, A., Bhattacharya, J., Desai, M., Lembke, A., Ratliff, J. K. 2019

  Abstract

  BACKGROUND: The morbidity and mortality associated with opioid and benzodiazepine co-prescription is a pressing national concern. Little is known about patterns of opioid and benzodiazepine use in patients with acute low back pain or lower extremity pain.OBJECTIVE: To characterize patterns of opioid and benzodiazepine prescribing among opioid-naive, newly diagnosed low back pain (LBP) or lower extremity pain (LEP) patients and to investigate the relationship between benzodiazepine prescribing and long-term opioid use.DESIGN/SETTING: We performed a retrospective analysis of a commercial database containing claims for more than 75 million enrollees in the USA.PARTICIPANTS: Participants were adult patients newly diagnosed with LBP or LEP between 2008 and 2015 who did not have a red flag diagnosis, had not received an opioid prescription in the 6months prior to diagnosis, and had 12months of continuous enrollment after diagnosis.MAIN OUTCOMES AND MEASURES: Among patients receiving at least one opioid prescription within 12months of diagnosis, we defined discrete patterns of benzodiazepine prescribing-continued use, new use, stopped use, and never use. We tested the association of these prescription patterns with long-term opioid use, defined as six or more fills within 12months.RESULTS: We identified 2,497,653 opioid-naive patients with newly diagnosed LBP or LEP. Between 2008 and 2015, 31.9% and 11.5% of these patients received opioid and benzodiazepine prescriptions, respectively, within 12months of diagnosis. Rates of opioid prescription decreased from 34.8% in 2008 to 27.0% in 2015 (P<0.001); however, prescribing of benzodiazepines only decreased from 11.6% in 2008 to 10.8% in 2015. Patients with continued or new benzodiazepine use consistently used more opioids than patients who never used or stopped using benzodiazepines during the study period (one-way ANOVA, P<0.001). For patients with continued and new benzodiazepine use, the odds ratio of long-term opioid use compared with those never prescribed a benzodiazepine was 2.99 (95% CI, 2.89-3.08) and 2.68 (95% CI, 2.62-2.75), respectively.LIMITATIONS: This study used administrative claims analyses, which rely on accuracy and completeness of diagnostic, procedural, and prescription codes.CONCLUSION: Overall opioid prescribing for low back pain or lower extremity pain decreased substantially during the study period, indicating a shift in management within the medical community. Rates of benzodiazepine prescribing, however, remained at approximately 11%. Concurrent prescriptions of benzodiazepines and opioids after LBP or LEP diagnosis were associated with increased risk of long-term opioid use.

  View details for DOI 10.1007/s11606-019-05549-8

  View details for PubMedID 31720966

• Rethinking Opioid Dose Tapering, Prescription Opioid Dependence, and Indications for Buprenorphine. Annals of internal medicine Chou, R., Ballantyne, J., Lembke, A. 2019

  View details for DOI 10.7326/M19-1488

  View details for PubMedID 31450240

• Patients Maintained on Buprenorphine for Opioid Use Disorder Should Continue Buprenorphine Through the Perioperative Period PAIN MEDICINE Lembke, A., Ottestad, E., Schmiesing, C. 2019; 20 (3): 425–28

  View details for DOI 10.1093/pm/pny019

  View details for Web of Science ID 000467966600001

• Patients Maintained on Buprenorphine for Opioid Use Disorder Should Continue Buprenorphine Through the Perioperative Period. Pain medicine (Malden, Mass.) Lembke, A., Ottestad, E., Schmiesing, C. 2019; 20 (3): 425–28

  View details for PubMedID 29452378

• Initiating Opioid Agonist Treatment for Opioid Use Disorder in the Inpatient Setting: A Teachable Moment. JAMA internal medicine Raheemullah, A., Lembke, A. 2019

  View details for PubMedID 30640372

• Buprenorphine Induction Without Opioid Withdrawal: A Case Series of 15 Opioid-Dependent Inpatients Induced on Buprenorphine Using Microdoses of Transdermal Buprenorphine. American journal of therapeutics Raheemullah, A. n., Lembke, A. n. 2019

  View details for DOI 10.1097/MJT.0000000000001108

  View details for PubMedID 31833872

• Exercise and Addiction LIFESTYLE PSYCHIATRY Lembke, A., Raheemullah, A., Noordsy, D. L. 2019: 127–39

  View details for Web of Science ID 000552225000010

• Substance Use Among Older Adults: Ethical Issues. Focus (American Psychiatric Publishing) Ogbonna, C. I., Lembke, A. n. 2019; 17 (2): 143–47

  View details for DOI 10.1176/appi.focus.20180041

  View details for PubMedID 31975971

  View details for PubMedCentralID PMC6527007

• Qualitative Assessment of Clerkship Students' Perspectives of the Topics of Pain and Addiction in their Preclinical Curriculum. Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry Raber, I., Ball, A., Papac, J., Aggarwal, A., Sussman, R., Basaviah, P., Newmark, J., Lembke, A. 2018; 42 (5): 664-667

  Abstract

  A majority of physicians feel poorly trained in the treatment of chronic pain and addiction. As such, it is critical that medical students receive appropriate education in both pain management and addiction. The purpose of this study was to assess the pre-clinical curriculum in pain medicine and addiction from the perspective of students after they had completed their pre-clinical training and to assess what they perceived as the strengths and weaknesses of their training.The authors conducted focused interviews among clinical medical students who had completed at least 6 months of clerkships. The interviews targeted the students' retrospective opinions about the pre-clinical curriculum and their preparedness for clinical encounters with either pain or addiction-related issues during their rotations. Coders thematically analyzed the de-identified interview transcripts, with consensus reached through discussion and code modification.Themes that emerged through the focused interviews included: fragmented curricular structure (and insufficient time) for pain and addiction medicine, not enough specific treatment strategies for pain or addiction, especially for complex clinical scenarios, and lack of a trained work-force to provide guidance in the management of pain and addiction.This study demonstrated the feasibility of gathering student perspectives to inform changes to improve the pre-clinical curriculum in pain and addiction medicine. Students identified multiple areas for improvement at the pre-clerkship level, which have informed updates to the curriculum. More research is needed to determine if curricular changes based on student feedback lead to improved learning outcomes.

  View details for DOI 10.1007/s40596-018-0927-1

  View details for PubMedID 29704194

• Perioperative Considerations for the Patient with Opioid Use Disorder on Buprenorphine, Methadone, or Naltrexone Maintenance Therapy. Anesthesiology clinics Harrison, T. K., Kornfeld, H., Aggarwal, A. K., Lembke, A. 2018; 36 (3): 345–59

  Abstract

  As part of a national effort to combat the current US opioid epidemic, use of currently Food and Drug Administration-approved drugs for the treatment of opioid use disorder/opioid addiction (buprenorphine, methadone, and naltrexone) is on the rise. To provide optimal pain control and minimize the risk of relapse and overdose, providers need to have an in-depth understanding of how to manage these medications in the perioperative setting. This article reviews key principles and discusses perioperative considerations for patients with opioid use disorder on buprenorphine, methadone, or naltrexone.

  View details for PubMedID 30092933

• The Opioid Epidemic as a Watershed Moment for Physician Training in Addiction Medicine ACADEMIC PSYCHIATRY Lembke, A., Humphreys, K. 2018; 42 (2): 269–72

  View details for PubMedID 29536394

• Our Other Prescription Drug Problem NEW ENGLAND JOURNAL OF MEDICINE Lembke, A., Papac, J., Humphreys, K. 2018; 378 (8): 693–95

  View details for PubMedID 29466163

• Qualitative Assessment of Clerkship Students' Perspectives of the Topics of Pain and Addiction in their Preclinical Curriculum Academic Psychiatry Raber, I., Ball, A., Papac, J., Aggarwal, A., Sussman, R., Basaviah, P., Newmark, J., Lembke, A. 2018: 664–67

  Abstract

  A majority of physicians feel poorly trained in the treatment of chronic pain and addiction. As such, it is critical that medical students receive appropriate education in both pain management and addiction. The purpose of this study was to assess the pre-clinical curriculum in pain medicine and addiction from the perspective of students after they had completed their pre-clinical training and to assess what they perceived as the strengths and weaknesses of their training.The authors conducted focused interviews among clinical medical students who had completed at least 6 months of clerkships. The interviews targeted the students' retrospective opinions about the pre-clinical curriculum and their preparedness for clinical encounters with either pain or addiction-related issues during their rotations. Coders thematically analyzed the de-identified interview transcripts, with consensus reached through discussion and code modification.Themes that emerged through the focused interviews included: fragmented curricular structure (and insufficient time) for pain and addiction medicine, not enough specific treatment strategies for pain or addiction, especially for complex clinical scenarios, and lack of a trained work-force to provide guidance in the management of pain and addiction.This study demonstrated the feasibility of gathering student perspectives to inform changes to improve the pre-clinical curriculum in pain and addiction medicine. Students identified multiple areas for improvement at the pre-clerkship level, which have informed updates to the curriculum. More research is needed to determine if curricular changes based on student feedback lead to improved learning outcomes.

  View details for DOI 10.1007/s40596-018-0927-1

• Tapering Patients Off of Benzodiazepines. American family physician Ogbonna, C. I., Lembke, A. 2017; 96 (9): 606-610

  View details for PubMedID 29094883

• HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition MOLECULAR PSYCHIATRY Keller, J., Gomez, R., Williams, G., Lembke, A., Lazzeroni, L., urphy, G. M., Schatzberg, A. F. 2017; 22 (4): 527-536

  Abstract

  The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology and HPA genetic variation play in cognitive performance. Patients with major depression with psychotic major depression (PMD) and with nonpsychotic major depression (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms and variation in genes, NR3C1 (glucocorticoid receptor; GR) and NR3C2 (mineralocorticoid receptor; MR) that encode for GRs and MRs, predicted cognitive performance. Beyond the effects of cortisol, demographics and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and HR. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory.Molecular Psychiatry advance online publication, 16 August 2016; doi:10.1038/mp.2016.120.

  View details for DOI 10.1038/mp.2016.120

  View details for Web of Science ID 000397099900006

• Extended treatment for cigarette smoking cessation: A randomized control trial. Addiction Laude, J. R., Bailey, S. R., Crew, E., Varady, A., Lembke, A., McFall, D., Jeon, A., Killen, D., Killen, J. D., David, S. P. 2017

  Abstract

  To test the potential benefit of extending cognitive-behavioral therapy (CBT) relative to not extending CBT on long-term abstinence from smoking.Two-group parallel randomised controlled trial. Patients were randomized to receive non-extended CBT (n = 111) or extended CBT (n = 112) following a 26-week open-label treatment.Community clinic in the USA.219 smokers (mean age: 43 years; mean cigarettes/day: 18).All participants received 10 weeks of combined CBT + bupropion sustained release (bupropion SR) + nicotine patch and were continued on CBT and either no medications if abstinent, continued bupropion + nicotine replacement therapy (NRT) if increased craving or depression scores, or varenicline if still smoking at 10 weeks. Half of participants were randomized at 26 weeks to extended CBT (E-CBT) through week 48 and half to non-extended CBT (no additional CBT sessions).The primary outcome was expired CO-confirmed, seven-day point-prevalence (PP) at 52-week and 104-week follow-up. Analyses were based on intention-to-treat.PP-abstinence rates at the 52-week follow-up were comparable across non-extended CBT (40%) and E-CBT (39%) groups [OR 0.99; 95% CI (0.55,1.78)]. A similar pattern was observed across non-extended CBT (39%) and E-CBT (33%) groups at the 104-week follow-up [OR 0.79; 95% CI (0.44,1.40)].Prolonging cognitive-behavioral therapy from 26 to 48 weeks does not appear to improve long-term abstinence from smoking.

  View details for DOI 10.1111/add.13806

  View details for PubMedID 28239942

• Reasons for Benzodiazepine Use Among Persons Seeking Opioid Detoxification. Journal of substance abuse treatment Stein, M. D., Kanabar, M., Anderson, B. J., Lembke, A., Bailey, G. L. 2016; 68: 57-61

  Abstract

  Over the past decade, patients admitted to addiction treatment programs have reported increasing rates of concurrent opioid and benzodiazepine (BZD) use. This drug combination places individuals at high risk for accidental overdose. Little is known about reasons for BZD use among individuals seeking treatment for opioid use disorders.We surveyed consecutive persons initiating inpatient opioid detoxification and identified 176 out of 438 who reported BZD use in the past 30 days and/or had a positive toxicology.Forty percent of persons surveyed used a BZD in the month prior to admission, and 25% of these met criteria for BZD dependence (DSM IV). BZD users averaged 32.0 years of age, 63.6% were male, 85.2% used heroin, and reported, on average, 13.3 (±11.2) days of BZD use during the past month. Alprazolam (Xanax) was the most commonly used BZD (52%), and buying it on the street the most common source (48%). The most commonly reported reason for BZD use was 'to manage anxiety' (42.6%), followed by 'to get or enhance a high' (27.7%), 'to help with sleep' (11.4%), and 'to decrease opioid withdrawal' (10.2%). The most common reason for BZD use was significantly associated (p<.001) with most likely source of BZDs, with persons who got their BZDs from a prescriber (23%) more likely to report BZD anxiety as their primary reason for use, while persons who bought BZDs on "the street" (48%) had the highest likelihood of reporting using BZD to get or enhance a high. Participants using BZDs most commonly for anxiety did not endorse lower anxiety than those using BZDs for other reasons.Two in five persons seeking detoxification for an opioid use disorder used a BZD in the prior month. Anxiety was the most common reason patients reported using a benzodiazepine, but they also reported using BZDs to enhance a 'high' and manage opioid withdrawal. Evidence-based discussions about the risks of combining BZDs and opioids, and alternatives to BZDs should be a high priority in detoxification settings.

  View details for DOI 10.1016/j.jsat.2016.06.008

  View details for PubMedID 27431047

  View details for PubMedCentralID PMC4955948

• Use of Opioid Agonist Therapy for Medicare Patients in 2013. JAMA psychiatry Lembke, A., Chen, J. H. 2016; 73 (9): 990-992

  View details for DOI 10.1001/jamapsychiatry.2016.1390

  View details for PubMedID 27438334

• HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition. Molecular psychiatry Keller, J., Gomez, R., Williams, G., Lembke, A., Lazzeroni, L., Murphy, G. M., Schatzberg, A. F. 2016

  Abstract

  The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology and HPA genetic variation play in cognitive performance. Patients with major depression with psychotic major depression (PMD) and with nonpsychotic major depression (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms and variation in genes, NR3C1 (glucocorticoid receptor; GR) and NR3C2 (mineralocorticoid receptor; MR) that encode for GRs and MRs, predicted cognitive performance. Beyond the effects of cortisol, demographics and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and HR. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory.Molecular Psychiatry advance online publication, 16 August 2016; doi:10.1038/mp.2016.120.

  View details for DOI 10.1038/mp.2016.120

  View details for PubMedID 27528460

• Weighing the Risks and Benefits of Chronic Opioid Therapy AMERICAN FAMILY PHYSICIAN Lembke, A., Humphreys, K., Newmark, J. 2016; 93 (12): 982-990

  Abstract

  Evidence supports the use of opioids for treating acute pain. However, the evidence is limited for the use of chronic opioid therapy for chronic pain. Furthermore, the risks of chronic therapy are significant and may outweigh any potential benefits. When considering chronic opioid therapy, physicians should weigh the risks against any possible benefits throughout the therapy, including assessing for the risks of opioid misuse, opioid use disorder, and overdose. When initiating opioid therapy, physicians should consider buprenorphine for patients at risk of opioid misuse, opioid use disorder, and overdose. If and when opioid misuse is detected, opioids do not necessarily need to be discontinued, but misuse should be noted on the problem list and interventions should be performed to change the patient's behavior. If aberrant behavior continues, opioid use disorder should be diagnosed and treated accordingly. When patients are discontinuing opioid therapy, the dosage should be decreased slowly, especially in those who have intolerable withdrawal. It is not unreasonable for discontinuation of chronic opioid therapy to take many months. Benzodiazepines should not be coprescribed during chronic opioid therapy or when tapering, because some patients may develop cross-dependence. For patients at risk of overdose, naloxone should be offered to the patient and to others who may be in a position to witness and reverse opioid overdose.

  View details for Web of Science ID 000377633800003

  View details for PubMedID 27304767

• A call to include people with mental illness and substance use disorders alongside 'regular' smokers in smoking cessation research. Tobacco control Lembke, A., Humphreys, K. 2016; 25 (3): 261-2

  Abstract

  This commentary points out that smoking is increasingly concentrated among people with psychiatric problems and other substance use disorders (eg, alcohol use disorder), and argues that for clinical, ethical and efficiency reasons, such individuals should be routinely enrolled in smoking cessation research.

  View details for DOI 10.1136/tobaccocontrol-2014-052215

  View details for PubMedID 25882685

• Distribution of Opioids by Different Types of Medicare Prescribers. JAMA internal medicine Chen, J. H., Humphreys, K., Shah, N. H., Lembke, A. 2016; 176 (2): 259-61

  View details for DOI 10.1001/jamainternmed.2015.6662

  View details for PubMedID 26658497

  View details for PubMedCentralID PMC5374118

• Assessment of provider attitudes toward #naloxone on Twitter. Substance abuse Haug, N. A., Bielenberg, J., Linder, S. H., Lembke, A. 2016; 37 (1): 35-41

  Abstract

  As opioid overdose rates continue to pose a major public health crisis, the need for naloxone treatment by emergency first responders is critical. Little is known about the views of those who administer naloxone. The current study examines attitudes of health professionals on the social media platform Twitter to better understand their perceptions of opioid users, the role of naloxone, and potential training needs.Public comments on Twitter regarding naloxone were collected for a period of 3 consecutive months. The occupations of individuals who posted tweets were identified through Twitter profiles or hashtags. Categories of emergency service first responders and medical personnel were created. Qualitative analysis using a grounded theory approach was used to produce thematic content. The relationships between occupation and each theme were analyzed using Pearson chi-square statistics and post hoc analyses.A total of 368 individuals posted 467 naloxone-related tweets. Occupations consisted of professional first responders such as emergency medical technicians (EMTs), firefighters, and paramedics (n = 122); law enforcement officers (n = 70); nurses (n = 62); physicians (n = 48); other health professionals including pharmacists, pharmacy technicians, counselors, and social workers (n = 31); naloxone-trained individuals (n = 12); and students (n = 23). Primary themes included burnout, education and training, information seeking, news updates, optimism, policy and economics, stigma, and treatment. The highest levels of burnout, fatigue, and stigma regarding naloxone and opioid overdose were among nurses, EMTs, other health care providers, and physicians. In contrast, individuals who self-identified as "naloxone-trained" had the highest optimism and the lowest amount of burnout and stigma.Provider training and refinement of naloxone administration procedures are needed to improve treatment outcomes and reduce provider stigma. Social networking sites such as Twitter may have potential for offering psychoeducation to health care providers.

  View details for DOI 10.1080/08897077.2015.1129390

  View details for PubMedID 26860229

• Retrospective analysis of changing characteristics of treatment-seeking smokers: implications for further reducing smoking prevalence. BMJ open Leyro, T. M., Crew, E. E., Bryson, S. W., Lembke, A., Bailey, S. R., Prochaska, J. J., Henriksen, L., Fortmann, S. P., Killen, J. D., Killen, D. T., Hall, S. M., David, S. P. 2016; 6 (6)

  Abstract

  The goal of the current study was to empirically compare successive cohorts of treatment-seeking smokers who enrolled in randomised clinical trials in a region of the USA characterised by strong tobacco control policies and low smoking prevalence, over the past three decades.Retrospective treatment cohort comparison.Data were collected from 9 randomised clinical trials conducted at Stanford University and the University of California, San Francisco, between 1990 and 2013.Data from a total of 2083 participants were included (Stanford, n=1356; University of California San Francisco, n=727).One-way analysis of variance and covariance, χ(2) and logistic regression analyses were used to examine relations between nicotine dependence, cigarettes per day, depressive symptoms and demographic characteristics among study cohorts.Similar trends were observed at both settings. When compared to earlier trials, participants in more recent trials smoked fewer cigarettes, were less nicotine-dependent, reported more depressive symptoms, were more likely to be male and more likely to be from a minority ethnic/racial group, than those enrolled in initial trials (all p's<0.05). Analysis of covariances revealed that cigarettes per day, nicotine dependence and current depressive symptom scores were each significantly related to trial (all p's<0.001).Our findings suggest that more recent smoking cessation treatment-seeking cohorts in a low prevalence region were characterised by less smoking severity, more severe symptoms of depression and were more likely to be male and from a minority racial/ethnic group.

  View details for DOI 10.1136/bmjopen-2015-010960

  View details for PubMedID 27357195

• A qualitative study of treatment-seeking heroin users in contemporary China. Addiction science & clinical practice Lembke, A., Zhang, N. 2015; 10: 23-?

  Abstract

  Heroin has emerged as the primary drug of concern in China, with as many as three million contemporary users. Once a Chinese citizen has been identified by Chinese law enforcement as a 'drug addict', that individual is 'registered' in an official government tracking system for the rest of his or her life, independent of verified rehabilitation and recovery. Most of what is known about heroin users in China is based on studies of registered heroin users participating, often involuntarily, in government-sponsored treatment.Using Grounded Theory Methodology, we collected and analyzed in-depth interviews of heroin users voluntarily seeking treatment at a new, non-government-sponsored, for-profit, addiction treatment hospital in Beijing, China.We identified three major themes among our participants: (1) intense social stigma towards individuals with drug addiction; (2) a desire for anonymous, confidential treatment to avoid social stigma and the loss of personal freedom that accompanies participation in government-sponsored treatment; and (3) a deep mistrust of government-sponsored treatment and a search for more effective alternatives.Despite a desire for treatment, our subjects were reluctant to access government-sponsored treatment facilities because of fear of a stigmatized identity, fear of loss of personal freedom, and lack of faith in the efficacy and safety of government-sponsored treatments. Their willingness to pay cash at a new, non-government-sponsored, addiction treatment facility illustrates the lengths to which they will go to remain 'unregistered' and to discover better alternatives. That the Chinese government allows such facilities to operate outside of government surveillance suggests a new openness to alternative options to combat China's rising drug epidemic. The efficacy of these alternative options, however, remains in question.

  View details for DOI 10.1186/s13722-015-0044-3

  View details for PubMedID 26538288

  View details for PubMedCentralID PMC4672521

• Plasma oxytocin concentrations are lower in depressed vs. healthy control women and are independent of cortisol. Journal of psychiatric research Yuen, K. W., Garner, J. P., Carson, D. S., Keller, J., Lembke, A., Hyde, S. A., Kenna, H. A., Tennakoon, L., Schatzberg, A. F., Parker, K. J. 2014; 51: 30-36

  Abstract

  The neuropeptide oxytocin (OT) promotes social behavior and attenuates stress responsivity in mammals. Recent clinical evidence suggests OT concentrations may be dysregulated in major depression. This study extends previous research by testing whether: 1) OT concentrations vary systematically in depressive disorders with and without hypercortisolemia, 2) gender differences in OT concentrations are observed in depressed vs. healthy control participants, and 3) OT concentrations are predictive of clinical phenotypes. Plasma OT concentrations of psychotic major depressive (PMD; n = 14: 10 female, 4 male), non-psychotic major depressive (NPMD; n = 17: 12 female, 5 male), and non-depressed, healthy control (n = 19: 11 female, 8 male) participants were assayed at 2000, 2400, 0400, and 0800 h. Plasma cortisol concentrations were quantified at 2300 h, and clinical phenotypes were determined. As expected, PMD participants, compared to NPMD and healthy control participants, showed higher plasma cortisol concentrations. Although both depressed groups showed similar OT concentrations, a significant interaction effect between group and gender was observed. Specifically, depressed females exhibited lower mean OT concentrations than depressed males. Further, depressed vs. healthy control female participants exhibited lower mean OT concentrations, whereas depressed vs. healthy control male participants showed a trend in the opposite direction. OT concentrations were also predictive of desirability, drug dependence, and compulsivity scores as measured by the Million Clinical Multiaxial Inventory-III. All findings were independent of cortisol. These data suggest that OT signaling may provide a mechanism by which to better understand female-biased risk to develop depressive disorders and that plasma OT concentrations may be a useful biomarker of certain clinical phenotypes.

  View details for DOI 10.1016/j.jpsychires.2013.12.012

  View details for PubMedID 24405552

• HPA axis genetic variation, cortisol and psychosis in major depression. Molecular psychiatry Schatzberg, A. F., Keller, J., Tennakoon, L., Lembke, A., Williams, G., Kraemer, F. B., Sarginson, J. E., Lazzeroni, L. C., Murphy, G. M. 2014; 19 (2): 220-227

  Abstract

  Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depression (PMD); 26 patients with non-psychotic major depression (NPMD); and 29 HCs. Collection of genetic material was added one third of the way into a larger study on cortisol, cognition and psychosis in major depression. Subjects were assessed using the Brief Psychiatric Rating Scale, the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Blood was collected hourly for determination of cortisol from 1800 to 0900 h and for the assessment of alleles for six genes involved in HPA axis regulation. Two of the six genes contributed significantly to cortisol levels, psychosis measures or depression severity. After accounting for age, depression and psychosis, and medication status, only allelic variation for the glucocorticoid receptor (GR) gene accounted for a significant variance for mean cortisol levels from 1800 to 0100 h (r(2)=0.288) and from 0100 to 0900 h (r(2)=0.171). In addition, GR and corticotropin-releasing hormone receptor 1 (CRHR1) genotypes contributed significantly to psychosis measures and CRHR1 contributed significantly to depression severity rating.Molecular Psychiatry advance online publication, 29 October 2013; doi:10.1038/mp.2013.129.

  View details for DOI 10.1038/mp.2013.129

  View details for PubMedID 24166410

• Recovery-oriented policy and care systems in the UK and USA. Drug and alcohol review Humphreys, K., Lembke, A. 2014; 33 (1): 13-18

  Abstract

  The concept of recovery has been an influence on addicted individuals for many decades. But only in the past 15 years has the concept had a purchase in the world of public policy. In the USA, federal and state officials have promulgated policies intended to foster 'recovery-oriented systems of care' and have ratified recovery-supportive laws and regulations. Though of more recent vintage and therefore less developed, recovery policy initiatives are also being implemented in the UK. The present paper describes recovery-oriented policy in both countries and highlights key evaluations of the recovery-oriented interventions.

  View details for DOI 10.1111/dar.12092

  View details for PubMedID 24267515

• Clinical management of alcohol use disorders in the neurology clinic. Handbook of clinical neurology Lembke, A., Stanford, M. 2014; 125: 659-670

  Abstract

  Alcohol misuse adversely affects health outcomes, but alcohol misuse and alcohol use disorders (AUDs) are often ignored by healthcare providers in primary and specialty ambulatory care clinics. Data show that early identification and brief intervention for alcohol misuse in these settings can effectively reduce alcohol consumption and its medical sequelae. The aim of this chapter is to review the epidemiology of problematic alcohol use in ambulatory care settings, the diagnostic criteria for AUDs, the approach called SBIRT (screening, brief intervention and referral to treatment) as a model program to target alcohol misuse in everyday clinical practice, when and how to refer patients to resources beyond the clinic for their alcohol use problems, and the medical illnesses associated with AUDs.

  View details for DOI 10.1016/B978-0-444-62619-6.00039-2

  View details for PubMedID 25307603

• Pharmacotherapy for Alcohol Dependence: Perceived Treatment Barriers and Action Strategies Among Veterans Health Administration Service Providers PSYCHOLOGICAL SERVICES Harris, A. H., Ellerbe, L., Reeder, R. N., Bowe, T., Gordon, A. J., Hagedorn, H., Oliva, E., Lembke, A., Kivlahan, D., Trafton, J. A. 2013; 10 (4): 410-419

  Abstract

  Although access to and consideration of pharmacological treatments for alcohol dependence are consensus standards of care, receipt of these medications by patients is generally rare and highly variable across treatment settings. The goal of the present project was to survey and interview the clinicians, managers, and pharmacists affiliated with addiction treatment programs within Veterans Health Administration (VHA) facilities to learn about their perceptions of barriers and facilitators regarding greater and more reliable consideration of pharmacological treatments for alcohol dependence. Fifty-nine participants from 19 high-adopting and 11 low-adopting facilities completed the survey (facility-level response rate = 50%) and 23 participated in a structured interview. The top 4 barriers to increased consideration and use of pharmacotherapy for alcohol dependence were consistent across high- and low-adopting facilities and included perceived low patient demand, pharmacy procedures or formulary restrictions, lack of provider skills or knowledge regarding pharmacotherapy for alcohol dependence, and lack of confidence in treatment effectiveness. Low patient demand was rated as the most important barrier for oral naltrexone and disulfiram, whereas pharmacy or formulary restrictions were rated as the most important barrier for acamprosate and extended-release naltrexone. The 4 strategies rated across low- and high-adopting facilities as most likely to facilitate consideration and use of pharmacotherapy for alcohol dependence were more education to patients about existing medications, more education to health care providers about medications, increased involvement of physicians in treatment for alcohol dependence, and more compelling research on existing medications. This knowledge provides a foundation for designing, deploying, and evaluating targeted implementation efforts.

  View details for DOI 10.1037/a0030949

  View details for Web of Science ID 000327182400007

  View details for PubMedID 23356858

• From self-medication to intoxication: time for a paradigm shift. Addiction Lembke, A. 2013; 108 (4): 670-671

  View details for DOI 10.1111/add.12028

  View details for PubMedID 23496064

• Why doctors prescribe opioids to known opioid abusers. How cultural attitudes and financial disincentives affect the prescribing habits of physicians. Minnesota medicine Lembke, A. 2013; 96 (3): 36-37

  View details for PubMedID 23930467

• Altered brain function underlying verbal memory encoding and retrieval in psychotic major depression. Psychiatry research Kelley, R., Garrett, A., Cohen, J., Gomez, R., Lembke, A., Keller, J., Reiss, A. L., Schatzberg, A. 2013; 211 (2): 119-126

  Abstract

  Psychotic major depression (PMD) is associated with deficits in verbal memory as well as other cognitive impairments. This study investigated brain function in individuals with PMD during a verbal declarative memory task. Participants included 16 subjects with PMD, 15 subjects with non-psychotic major depression (NPMD) and 16 healthy controls (HC). Functional magnetic resonance imaging (fMRI) data were acquired while subjects performed verbal memory encoding and retrieval tasks. During the explicit encoding task, subjects semantically categorized words as either "man-made" or "not man-made." For the retrieval task, subjects identified whether words had been presented during the encoding task. Functional MRI data were processed using SPM5 and a group by condition ANOVA. Clusters of activation showing either a significant main effect of group or an interaction of group by condition were further examined using t-tests to identify group differences. During the encoding task, the PMD group showed lower hippocampus, insula, and prefrontal activation compared to HC. During the retrieval task, the PMD group showed lower recognition accuracy and higher prefrontal and parietal cortex activation compared to both HC and NPMD groups. Verbal retrieval deficits in PMD may be associated with deficient hippocampus function during encoding. Increased brain activation during retrieval may reflect an attempt to compensate for encoding deficits.

  View details for DOI 10.1016/j.pscychresns.2012.06.008

  View details for PubMedID 23149036

  View details for PubMedCentralID PMC3645926

• Altered brain function underlying verbal memory encoding and retrieval in psychotic major depression PSYCHIATRY RESEARCH-NEUROIMAGING Kelley, R., Garrett, A., Cohen, J., Gomez, R., Lembke, A., Keller, J., Reiss, A. L., Schatzberg, A. 2013; 211 (2): 119-126

  Abstract

  Psychotic major depression (PMD) is associated with deficits in verbal memory as well as other cognitive impairments. This study investigated brain function in individuals with PMD during a verbal declarative memory task. Participants included 16 subjects with PMD, 15 subjects with non-psychotic major depression (NPMD) and 16 healthy controls (HC). Functional magnetic resonance imaging (fMRI) data were acquired while subjects performed verbal memory encoding and retrieval tasks. During the explicit encoding task, subjects semantically categorized words as either "man-made" or "not man-made." For the retrieval task, subjects identified whether words had been presented during the encoding task. Functional MRI data were processed using SPM5 and a group by condition ANOVA. Clusters of activation showing either a significant main effect of group or an interaction of group by condition were further examined using t-tests to identify group differences. During the encoding task, the PMD group showed lower hippocampus, insula, and prefrontal activation compared to HC. During the retrieval task, the PMD group showed lower recognition accuracy and higher prefrontal and parietal cortex activation compared to both HC and NPMD groups. Verbal retrieval deficits in PMD may be associated with deficient hippocampus function during encoding. Increased brain activation during retrieval may reflect an attempt to compensate for encoding deficits.

  View details for DOI 10.1016/j.pscychresns.2012.06.008

  View details for Web of Science ID 000316828400004

  View details for PubMedID 23149036

  View details for PubMedCentralID PMC3645926

• The mineralocorticoid receptor agonist, fludrocortisone, differentially inhibits pituitary-adrenal activity in humans with psychotic major depression PSYCHONEUROENDOCRINOLOGY Lembke, A., Gomez, R., Tenakoon, L., Keller, J., Cohen, G., Williams, G. H., Kraemer, F. B., Schatzberg, A. F. 2013; 38 (1): 115-121

  Abstract

  Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been linked with major depression, particularly psychotic major depression (PMD), with mineralocorticoid receptors (MRs) playing a role in HPA-axis regulation and the pathophysiology of depression. Herein we hypothesize that the MR agonist fludrocortisone differentially inhibits the HPA axis of psychotic major depression subjects (PMDs), non-psychotic major depression subjects (NPMDs), and healthy control subjects (HCs).Fourteen PMDs, 16 NPMDs, and 19 HCs were admitted to the Stanford University Hospital General Clinical Research Center. Serum cortisol levels were sampled at baseline and every hour from 18:00 to 23:00h, when greatest MR activity is expected, on two consecutive nights. On the second afternoon at 16:00h all subjects were given 0.5mg fludrocortisone. Mean cortisol levels pre- and post-fludrocortisone and percent change in cortisol levels were computed.There were no significant group differences for cortisol at baseline: F(2,47)=.19, p=.83. There were significant group differences for post-fludrocortisone cortisol: F(2,47)=5.13, p=.01, which were significantly higher in PMDs compared to HCs (p=.007), but not compared to NPMDs (p=.18). There were no differences between NPMD's and HC's (p=.61). Also, PMDs had a lower percent change from baseline in cortisol levels at 2200h than NPMDs (p=.01) or HCs (p=.009).Individuals with psychotic major depression compared to healthy control subjects have diminished feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in response to the mineralocorticoid receptor agonist fludrocortisone. To our knowledge, this is the first study to examine HPA axis response to MR stimulation in major depression (with and without psychosis), and only the third study to demonstrate that exogenously administered fludrocortisone can down-regulate the HPA axis in humans.

  View details for DOI 10.1016/j.psyneuen.2012.05.006

  View details for Web of Science ID 000313761000011

  View details for PubMedID 22727477

  View details for PubMedCentralID PMC3633490

• Time to Abandon the Self-Medication Hypothesis in Patients with Psychiatric Disorders AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE Lembke, A. 2012; 38 (6): 524-529

  Abstract

  The Self-Medication Hypothesis (SMH) of addictive disorders as articulated by Edward Khantzian in his seminal 1985 paper postulates that individuals with psychiatric disorders use substances to relieve psychiatric symptoms and that this pattern of usage predisposes them to addiction. Khantzian's SMH also postulates that the preferred substance is not random, but is based on the unique pharmacological properties of the substance. For example, an individual with attention deficit disorder would prefer amphetamines to alcohol, due to its stimulating properties, whereas an individual with anxiety would prefer alcohol to amphetamines, due to its anxiolytic properties. Finally, Khantzian's SMH implies that treating the underlying psychiatric disorder will improve or resolve the problems of addiction. AIMS AND RESULTS: A review of the scientific literature demonstrates a striking lack of robust evidence in support of the SMH as put forth by Khantzian.Nonetheless, the SMH has had a profound influence on medical and lay culture, as well as clinical care. Although originally formulated as a compassionate explanation for addiction in those with psychiatric disorders, the SMH does not provide, as originally intended, a "useful rationale" for guiding treatment and instead has led to under-recognition and under-treatment of substance use disorders.

  View details for DOI 10.3109/00952990.2012.694532

  View details for Web of Science ID 000309667200002

  View details for PubMedID 22924576

• Why Doctors Prescribe Opioids to Known Opioid Abusers NEW ENGLAND JOURNAL OF MEDICINE Lembke, A. 2012; 367 (17): 1580-1581

  View details for DOI 10.1056/NEJMp1208498

  View details for Web of Science ID 000310131700002

  View details for PubMedID 23094719

• The relationships of positive and negative symptoms with neuropsychological functioning and their ability to predict verbal memory in psychotic major depression PSYCHIATRY RESEARCH Che, A. M., Gomez, R. G., Keller, J., Lembke, A., Tennakoon, L., Cohen, G. H., Schatzberg, A. F. 2012; 198 (1): 34-38

  Abstract

  Neuropsychological functioning, in relation to positive and negative symptoms in psychotic major depression (PMD), has not been as thoroughly studied as it has been in schizophrenia. Thus, the current study investigated the associations between positive and negative symptoms with cognitive functioning, with an emphasis on verbal memory in PMD. Attention, working memory, and the executive functioning domains were analyzed among 49 PMD participants. Positive symptoms did not correlate significantly with any measures of verbal memory but did correlate with one measure of attention, working memory, and executive functioning. Negative symptoms correlated significantly with two California Verbal Learning Test-II (CVLT-II) measures of verbal memory and three measures of executive function. Hierarchical regressions were conducted to determine if negative symptoms could predict verbal memory performance after controlling for depression. Of the two verbal memory measures, negative symptoms significantly explained additional variance for CVLT Recognition, but not for CVLT Trials 1-5 total score. Our results provide some evidence that, consistent with the schizophrenia literature, negative symptoms contributed more to verbal memory deficits in PMD than positive symptoms, regardless of depression severity.

  View details for DOI 10.1016/j.psychres.2011.12.001

  View details for Web of Science ID 000313848200007

  View details for PubMedID 22410589

• Alcohol Screening Scores and the Risk of New-Onset Gastrointestinal Illness or Related Hospitalization JOURNAL OF GENERAL INTERNAL MEDICINE Lembke, A., Bradley, K. A., Henderson, P., Moos, R., Harris, A. H. 2011; 26 (7): 777-782

  Abstract

  Excessive alcohol use is associated with a variety of negative health outcomes, including liver disease, upper gastrointestinal bleeding, and pancreatitis.To determine the 2-year risk of gastrointestinal-related hospitalization and new-onset gastrointestinal illness based on alcohol screening scores.Retrospective cohort study.Male (N = 215, 924) and female (N = 9,168) outpatients who returned mailed questionnaires and were followed for 24 months.Alcohol Use Disorder Identification Test-Consumption Questionnaire (AUDIT-C), a validated three-item alcohol screening questionnaire (0-12 points).Two-year risk of hospitalization with a gastrointestinal disorder was increased in men with AUDIT-C scores of 5-8 and 9-12 (OR 1.54, 95% CI = 1.27-1.86; and OR 3.27; 95% CI = 2.62-4.09 respectively), and women with AUDIT-C scores of 9-12 (OR 6.84, 95% CI = 1.85 - 25.37). Men with AUDIT-C scores of 5-8 and 9-12 had increased risk of new-onset liver disease (OR 1.49, 95% CI = 1.30-1.71; and OR 2.82, 95% CI = 2.38-3.34 respectively), and new-onset of upper gastrointestinal bleeding (OR 1.28, 95% CI = 1.05-1.57; and OR 2.14, 95% CI = 1.54-2.97 respectively). Two-year risk of new-onset pancreatitis in men with AUDIT -C scores 9-12 was also increased (OR 2.14; 95% CI = 1.54-2.97).Excessive alcohol use as determined by AUDIT-C is associated with 2-year increased risk of gastrointestinal-related hospitalization in men and women and new-onset liver disease, upper gastrointestinal bleeding, and pancreatitis in men. These results provide risk information that clinicians can use in evidence-based conversations with patients about their alcohol consumption.

  View details for DOI 10.1007/s11606-011-1688-7

  View details for Web of Science ID 000291701200019

  View details for PubMedID 21455813

  View details for PubMedCentralID PMC3138581

• Depression and smoking cessation: does the evidence support psychiatric practice? Neuropsychiatric disease and treatment Lembke, A., Johnson, K., DeBattista, C. 2007; 3 (4): 487-493

  Abstract

  Depression and smoking are highly comorbid. The vast majority of psychiatrists treating depressed patients do not target or treat nicotine dependence, and many inpatient psychiatric facilities implicitly condone smoking by providing 'smoke breaks'. The reasons for failure to treat are unclear, but are probably linked to the notion that depressed smokers are neither willing nor able to quit, and will become more depressed if they try. We review the clinical evidence on depression and smoking cessation, and find little support for current psychiatric practice. Although quitting smoking does appear to pose a risk for the development of depression, this risk is not clearly higher in those with a past history of depression than those without. Depressed smokers are as capable as nondepressed smokers of quitting smoking, and at least one-quarter of depressed smokers is willing to try. Sustained abstinence may even lead to improvement in depressive disorders. More research is needed to understand the relationship between depression and quitting smoking, but current clinical evidence suggests more resiliency among depressed smokers than common clinical wisdom would dictate.

  View details for PubMedID 19300577

• Psychotherapy, symptom outcomes, and role functioning over one year among patients with bipolar disorder PSYCHIATRIC SERVICES Miklowitz, D. J., Otto, M. W., Wisniewski, S. R., Araga, M., Frank, E., Reilly-Harrington, N. A., Lembke, A., Sachs, G. S. 2006; 57 (7): 959-965

  Abstract

  Randomized trials indicate that psychosocial interventions effective adjuncts to pharmacotherapy in bipolar disorder (1,2). A one-year naturalistic-prospective design was used to examine the association between psychotherapy use and the symptomatic and functional outcomes of patients with bipolar disorder.Patients with bipolar disorder in a depressed phase (N=248) were drawn from the first 1,000 enrollees (November 1999 to April 2002) in the Systematic Treatment Enhancement Program (STEP-BD), a study of patients with bipolar disorder receiving best-practice pharmacotherapy. Patients were seen clinics and interviewed every three months over one year regarding of psychotherapy services, symptoms, and role functioning. Mixed-effects regression models were used to examine whether the amount of psychotherapy the patients received during each three-month interval was associated with symptomatic or psychosocial functioning during the same or a subsequent three-month interval.During the study year, percent of the patients had at least one psychotherapy session. Among patients who began an interval with severe depressive symptoms or low functioning, having more frequent sessions of psychotherapy was associated with less severe mood symptoms and better functioning in the same or a subsequent study interval. In contrast, among patients who began interval with less severe depressive symptoms or higher functioning, fewer psychotherapy sessions were associated with less severe depressive symptoms and greater functioning in the same or a subsequent interval.Intensive psychotherapy may be most applicable to severely ill patients with bipolar disorder, whereas briefer treatments may be adequate for less severely ill patients.

  View details for Web of Science ID 000238706800007

  View details for PubMedID 16816280

• Update on augmentation of antidepressant response in resistant depression. Current psychiatry reports DeBattista, C., Lembke, A. 2005; 7 (6): 435-440

  Abstract

  Most patients in acute depression trials fail to achieve remission with antidepressant monotherapy. Many patients seem to require more than one medication to achieve remission or adequate response. Augmentation strategies are commonly used in clinical practice, but most have been poorly studied. In addition, better-studied strategies, such as the use of lithium and thyroid augmentation, have not been well investigated in combination with newer antidepressants. Various novel strategies are being investigated as augmenting agents, including selective dopamine agonists, sex steroids, norepinephrine reuptake inhibitors, glucocorticoid-specific agents, and newer anticonvulsants. We review the status of augmentation strategies in the treatment of depression.

  View details for PubMedID 16318821

• Psychosocial service utilization by patients with bipolar disorders: data from the first 500 participants in the Systematic Treatment Enhancement Program. Journal of psychiatric practice Lembke, A., Miklowitz, D. J., Otto, M. W., Zhang, H., Wisniewski, S. R., Sachs, G. S., Thase, M. E., Ketter, T. A. 2004; 10 (2): 81-87

  Abstract

  Although patients with bipolar disorder have been shown to benefit from psychosocial interventions, the proportion that utilizes these interventions is unknown. We set out to clarify the determinants of psychosocial service utilization in adults with bipolar disorder.We investigated psychosocial service utilization among the first 500 patients admitted to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).In the 3 months prior to enrollment in STEP-BD, a majority of the patients (54%) were engaged in at least one psychosocial service modality in addition to pharmacotherapy. In order of decreasing frequency, these were therapy with a psychologist, self-help group, therapy with a social worker, and therapy with another type of provider. Bipolar patients with personality disorders (80% vs 20%, p = 0.0002), alcohol/drug abuse disorders (76% vs 24%, p = 0.0022), and anxiety disorders (60% vs 40%, p = 0.0043) received more psychosocial services than those without. Poorer global functioning also increased the likelihood of receiving services, whereas being married decreased service utilization.Psychosocial service utilization by outpatients with bipolar disorder is strongly linked to greater severity/complexity of illness. Potential moderators, such as insurance status and availability of care, should be examined in future studies.

  View details for PubMedID 15330403

• A prospective trial of modafinil as an adjunctive treatment of major depression JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY DeBattista, C., Lembke, A., Solvason, H. B., Ghebremichael, R., Poirier, J. 2004; 24 (1): 87-90

  Abstract

  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

• Current status of the utilization of antiepileptic treatments in mood, anxiety and aggression: Drugs and devices CLINICAL EEG AND NEUROSCIENCE Barry, J. J., Lembke, A., Bullock, K. D. 2004; 35 (1): 4-13

  Abstract

  Interventions that have been utilized to control seizures in people with epilepsy have been employed by the psychiatric community to treat a variety of disorders. The purpose of this review will be to give an overview of the most prominent uses of antiepileptic drugs (AEDs) and devices like the Vagus Nerve Stimulator (VNS) and Transcranial Magnetic Stimulation (TMS) in the treatment of psychiatric disease states. By far, the most prevalent use of these interventions is in the treatment of mood disorders. AEDs have become a mainstay in the effective treatment of Bipolar Affective Disorder (BAD). The U.S. Food and Drug Administration has approved the use of valproic acid for acute mania, and lamotrigine for BAD maintenance therapy. AEDs are also effectively employed in the treatment of anxiety and aggressive disorders. Finally, VNS and TMS are emerging as possibly useful tools in the treatment of more refractory depressive illness.

  View details for Web of Science ID 000223764000002

  View details for PubMedID 15112459

• Why is this special issue on women's professional development in psychiatry necessary? ACADEMIC PSYCHIATRY Lembke, A. 2004; 28 (4): 275-277

  View details for Web of Science ID 000226175400004

  View details for PubMedID 15673821

• A Friday in the life of an academic psychiatrist ACADEMIC PSYCHIATRY Lembke, A. 2003; 27 (3): 214-215

  View details for Web of Science ID 000185437700028

  View details for PubMedID 12969859

• A Day in the Life of an Academic Psychiatrist. Academic psychiatry Riba, M. B., Veith, R. C., Brodkey, A. C., Dimsdale, J. E., Zima, B. T., Stotland, N. L., Arambula, M. R., Polan, H. J., Moffic, H. S., Metzner, J. L., Lieff, S., Levy, B. R., Lu, F. G., Yager, J., Bonner, L. T., Muskin, P. R., Lembke, A., Borus, J. F., Jeste, D. V., Battaglia, J., Gabbard, G. O., Stewart, D. E., Arboleda-Flórez, J. 2003; 27 (3): 187-224

  View details for DOI 10.1176/appi.ap.27.3.187

  View details for PubMedID 28261751

• Safety of antidepressants in the elderly. Expert opinion on drug safety Sommer, B. R., Fenn, H., Pompei, P., DeBattista, C., Lembke, A., Wang, P., Flores, B. 2003; 2 (4): 367-383

  Abstract

  Until the 1980s, the two major classes of antidepressants, the tricyclics and the monoamine oxidase inhibitors (MAOIs), were effective but had severe side effects, requiring monitoring by psychiatrists. The past several years have brought new classes of antidepressants that are safer for the patient to take and far easier for the non-psychiatrist to prescribe. Whilst this is of enormous value, it leaves the physician with the dilemma of which one to prescribe. These new antidepressants cannot safely be used interchangeably. This paper will discuss each of the antidepressants presently available, with particular emphasis on safety in the elderly. Drug interactions, side effects and particular challenges to the older patient will be described. The authors will then advise a general strategy for prescribing antidepressants.

  View details for PubMedID 12904093

• Neural correlates of timbre change in harmonic sounds NEUROIMAGE Menon, V., Levitin, D. J., Smith, B. K., Lembke, A., Krasnow, B. D., Glazer, D., Glover, G. H., McAdams, S. 2002; 17 (4): 1742-1754

  Abstract

  Timbre is a major structuring force in music and one of the most important and ecologically relevant features of auditory events. We used sound stimuli selected on the basis of previous psychophysiological studies to investigate the neural correlates of timbre perception. Our results indicate that both the left and right hemispheres are involved in timbre processing, challenging the conventional notion that the elementary attributes of musical perception are predominantly lateralized to the right hemisphere. Significant timbre-related brain activation was found in well-defined regions of posterior Heschl's gyrus and superior temporal sulcus, extending into the circular insular sulcus. Although the extent of activation was not significantly different between left and right hemispheres, temporal lobe activations were significantly posterior in the left, compared to the right, hemisphere, suggesting a functional asymmetry in their respective contributions to timbre processing. The implications of our findings for music processing in particular and auditory processing in general are discussed.

  View details for DOI 10.1006/nimg.2002.1295

  View details for Web of Science ID 000179969800008

  View details for PubMedID 12498748

• The status of evidence-based guidelines and algorithms in the treatment of depression PSYCHIATRIC ANNALS Debattista, C., Trivedi, M. H., Kern, J. K., Lembke, A. 2002; 32 (11): 658-663

  View details for Web of Science ID 000179153800003

• Olanzapine in diverse syndromal and subsyndromal exacerbations of bipolar disorders BIPOLAR DISORDERS Janenawasin, S., Wang, P. W., Lembke, A., Schumacher, M., Das, B., Santosa, C. M., Mongkolcheep, J., Ketter, T. A. 2002; 4 (5): 328-334

  Abstract

  To evaluate effects of olanzapine in diverse exacerbations of bipolar disorders.Twenty-five evaluable bipolar disorder [14 bipolar I (BPI), 10 bipolar II (BPII) and one bipolar disorder not otherwise specified (BP NOS)] outpatients received open olanzapine (15 adjunctive, 10 monotherapy). Thirteen had elevated (11 syndromal, two subsyndromal) and 12 depressed (four syndromal, eight subsyndromal) mood symptoms of at least mild severity, with Clinical Global Impression-Severity (CGI-S) scores of at least 3. Only one had psychotic symptoms.With open olanzapine (15 adjunctive, 10 monotherapy), overall symptom severity (CGI-S) as well as mood elevation (Young Mania Rating Scale), depression (Hamilton and Montgomery-Asberg Depression Rating Scales), and anxiety (Hamilton Anxiety Rating Scale), rapidly decreased (significantly by days 2-3). Patients with the greatest baseline severity (CGI-S) had the greatest improvement. Fifteen of 25 (60%) patients responded. Time to consistent response was bimodal, with five early (by 0.5 +/- 0.3 weeks) and 10 late (by 7.0 +/- 1.9 weeks) responders. Early compared with late responders had 51% lower final olanzapine doses. Olanzapine was generally well tolerated, with sedation and weight gain the most common adverse effects.Olanzapine was effective in diverse exacerbations of bipolar disorders. The bimodal distribution of time to response and different final doses are consistent with differential mechanisms mediating early compared with late responses. Controlled studies are warranted to further explore these preliminary observations.

  View details for Web of Science ID 000178520500009

  View details for PubMedID 12479666

• Impaired recognition of facial emotion in mania AMERICAN JOURNAL OF PSYCHIATRY Lembke, A., Ketter, T. A. 2002; 159 (2): 302-304

  Abstract

  Recognition of facial emotion was examined in manic subjects to explore whether aberrant interpersonal interactions are related to impaired perception of social cues.Manic subjects with bipolar I disorder (N=8), euthymic subjects with bipolar I (N=8) or bipolar II (N=8) disorder, and healthy comparison subjects (N=10) matched pictures of faces to the words "fear," "disgust," "anger," "sadness," "surprise," and "happiness."The manic subjects showed worse overall recognition of facial emotion than all other groups. They showed worse recognition of fear and disgust than the healthy subjects. The euthymic bipolar II disorder subjects showed greater fear recognition than the manic and euthymic bipolar I disorder subjects.Impaired perception of facial emotion may contribute to behaviors in mania. Impaired recognition of fear and disgust, with relatively preserved recognition of other basic emotions, contrasts with findings for depression and is consistent with a mood-congruent positive bias.

  View details for Web of Science ID 000173727500020

  View details for PubMedID 11823275

• Depression in Individuals with Epilepsy. Current treatment options in neurology Barry, J. J., Huynh, N., Lembke, A. 2000; 2 (6): 571-585

  Abstract

  Depression in epilepsy patients is not only extremely common, but is often poorly recognized and inadequately treated. Depression can have significant consequences including increased medical utilization, poor quality of life, social disability, and mortality. Etiology of depression is multifaceted with prominent psychosocial determinants. Salient medical issues include iatrogenic causes, especially side effects of antiepileptic drugs (AEDs). In addition, seizures with increased frequency and with "forced normalization" can be associated with mood disturbance. After a thorough search for correctable causes, treatment should not be delayed, and should include both psychotherapy and pharmacologic therapies. Antidepressants remain the mainstay of pharmacologic intervention with the selective serotonin reuptake inhibitors (SSRIs) considered first-line treatment. Venlafaxine, nefazadone, and tricyclic antidepressants (TCAs) can also be used, but with some important caveats. Decreasing the seizure threshold is a common side effect of all antidepressants, but the risk can be minimized and should not prevent vigorous treatment of the depressive state. Other side effects present with varying frequency from the common (eg, sexual dysfunction as seen with SSRIs) to uncommon withdrawal reactions and rare complications of serotonin syndrome. Depression must also be considered a recurring disease, and when a successful regimen is ascertained, adequate continuation of treatment is a necessity. Care must be taken to treat the patient until complete resolution is achieved. Many patients with a major depressive disorder (MDD) will improve with inadequate treatment, but remain encumbered by a smoldering, low-level dysthymia that, in itself, can severely restrict the patient's quality of life.

  View details for PubMedID 11096781

• Isolated meningeal vasculopathy associated with Clostridium septicum infection NEUROLOGY Crowley, R. S., Lembke, A., Horoupian, D. S. 1997; 48 (1): 265-267

  Abstract

  A 28-year-old patient with acute lymphoblastic leukemia and neutropenia developed necrotizing enterocolitis and Clostridium septicum bacteremia, followed by rhabdomyolysis, skin rash, and acute neurologic changes. Numerous cortical leptomeningeal enhancements were present on head MRI. Meningeal and brain biopsy showed segmental, full-thickness lysis of smooth muscle cells of medium-sized meningeal vessels with overall preservation of the structure of the vessel wall.

  View details for Web of Science ID A1997WC67600049

  View details for PubMedID 9008531