The Journal of Clinical Psychopharmacology Podcast

Tachyphylaxis is a phenomenon described as the loss of response to a medication that was previously effective at an established dose. In a case report letter to the editors, Stefanie Cavalcanti, MD, Olga A. Lopez, MD, Simon Kung, MD, Jennifer L. Vande Voort, MD, Kristin Somers, MD, Mark A. Frye, MD, and Balwinder Singh, MD, MS, from the department of psychiatry and psychology at the Mayo Clinic, in Rochester, Minnesota, discuss “A Case of Tachyphylaxis After Long-Term Intravenous Racemic Ketamine for Treatment-Resistant Depression” in the May/June 2024 issue of the Journal of Clinical Psychopharmacology. In this podcast about the case report, two co-authors, Dr. Singh and Dr. Cavalcanti, discuss the compelling history of one 56-year-old woman with treatment-resistant recurrent major depressive disorder. Her depression, ongoing for 10 years, featured prominent symptoms of depressed mood, social isolation, low energy, decreased appetite, and anhedonia. Past medication trials included selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, mood stabilizers, antipsychotics, benzodiazepines, and bitemporal electroconvulsive therapy with limited benefit. Ketamine, which is used increasingly for treatment-resistant depression (TRD), and other psychiatric disorders, was tried next. Sustained clinical response was observed for the first 2 years of intravenous ketamine treatment despite ongoing life stressors. In the following years, a gradual reduction of response to subsequent ketamine infusions was observed in the patient, who required more frequent infusions to obtain the same response. The authors emphasize that “the extension of ketamine’s antidepressant effect with an increased dosage remains uncertain. … Ketamine has an addiction potential; thus, it is important to be mindful that increasing the ketamine dosage to address ketamine tachyphylaxis may enhance the potential for undesired consequences. Urgent studies investigating strategies to prolong ketamine’s efficacy in adults with TRD are required.”

The glucagon-like peptide 1 (GLP-1)–based diabetes and obesity drug semaglutide, with trade names Ozempic and Wegovy, will become the second best-selling drug in 2024, with estimated worldwide Ozempic sales of US ~$16 billion. Finally, the pharmacological treatment of obesity seems to have a breakthrough after decades of setbacks, with previous weight-loss medications withdrawn from the market because of serious side effects. In this podcast, the co-author of a guest editorial, “Glucagon-Like Peptide 1 Receptor Agonists in Psychiatry,” Hubertus Himmerich, MD, reviews the implications of GLP-1 drugs for psychiatry and healthcare globally. The article is published in the May/June 2024 issue of the Journal of Clinical Psychopharmacology. Dr. Himmerich, who is from the department of psychological medicine, Institute of Psychiatry, Psychology & Neuroscience at King's College in London, authored the editorial with Dr. Susan L. McElroy, of the Lindner Center of HOPE, Mason, OH, and the Department of Psychiatry and Behavioral Neuroscience at the University of Cincinnati College of Medicine.

Among most prescribers, bupropion is considered a substance of low misuse potential, with some studies showing lesser misuse potential than caffeine. However, several case reports exist of recreational bupropion misuse and diversion. This podcast, a discussion by authors of their bupropion systematic review, reports that snorting and intravenous injection of bupropion occur almost exclusively in patients with a substance use disorder history, with a preponderance of patients with stimulant use disorder or multiple substance use disorders. Users who divert bupropion from prescribed use describe a brief cocaine-like high of approximately 30 seconds to 5 minutes. The systematic review highlights the bupropion misuse potential in certain patient populations and serves to increase awareness among clinicians of unhealthy results of abuse. Additional patient screening, monitoring and follow-up, surveillance, and further research are needed to investigate and prevent bupropion misuse in at-risk patient populations. Sahil Munjal, MD, moderates a discussion conducted with his systematic review co-authors Greg Noe, BS, Kaushal Shah, MD, MPH, and Samantha Ongchuan, MD, on bupropion misuse. The article appears in the May/June 2024 issue of the Journal of Clinical Psychopharmacology. The authors are from Wake Forest University School of Medicine, the Department of Psychiatry at Atrium Wake Forest Baptist Health, and the Department of Psychiatry at Wake Forest University in Winston-Salem, NC.

In a guest editorial in the Journal of Clinical Psychopharmacology, authors Eric G. Smith and Kushani M. Patel discuss how case series and case reports can contribute to psychiatric treatment decisions. Their article in the March-Apil 2024 issue is titled “The Role of Case Series and Case Reports in Evidence-Based Medicine.” Dr. Smith is from the VA Bedford Healthcare System and the UMass Chan Medical School. Dr. Patel is from the Boston University Chobanian & Avedisian School of Medicine. Case reports and case series are justifiably far down in the hierarchy of evidence-based medicine, but there are specific clinical situations in which referring to case reports or case series can be of value. In this podcast, Dr. Smith discusses some of these circumstances, such as when there is no FDA-approved treatment for a disorder or when treating patients who have declined treatment with medications supported by higher levels of evidence such as randomized controlled trials. Additionally, case reports can assist in evaluating questions of safety.

“Rapid cycling” in bipolar disorder is defined by the occurrence of at least 4 episodes of mania, hypomania, depression, or mixed states during the preceding 12 months. Episodes are demarcated by partial or full remission for at least 2 months or a switch to an episode of opposite polarity. In this podcast, Dr. Ross J. Baldessarini of McLean Hospital and Harvard Medical School discusses the prevalence of rapid cycling and the challenges in its treatment. Rapid cycling is more common in women and is associated with an elevated risk of suicide. Dr. Baldessarini's comments are informed by recent efforts he and his colleagues undertook to synthesize reviews and meta-analyses on prevalence rates and response rates to treatment, as well as on their recently research on a cohort of 1261 bipolar disorder patients with or without rapid cycling who were followed up for at least 1 year. The March-April 2024 issue of the Journal of Clinical Psychopharmacology includes a commentary from Dr. Baldessarini, Dr. Alessandro Miola, Dr. Mark A. Frye, and Dr. Leonardo Tondo titled “Current Status and Treatment of Rapid Cycling Bipolar Disorder.”

Two articles in the March-April 2024 issue of the Journal of Clinical Psychopharmacology present research on glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a class of medications that has drawn considerable media attention in recent months for their ability to promote significant weight loss. The articles in JCP consider their use in specific populations of patients: individuals with bipolar disorder or eating disorders (in this case, atypical anorexia nervosa). This podcast features a discussion of the articles by authors Susan L. McElroy, MD; Anna Ward, ARPN; and Dr. Anna Guerdjikova, PhD, LISW, from the Lindner Center of HOPE in Mason, OH, and the University of Cincinnati. The first article, Liraglutide in Obese or Overweight Individuals With Stable Bipolar Disorder, reports on a placebo-controlled double-blind trial, which showed that compared with placebo, liraglutide was associated with greater reductions in percent change in body weight, and reductions in weight, body mass index, binge eating and hunger. Obesity is common among individuals with bipolar disorder, possibly contributing to their well-documented higher risk of cardiovascular-related mortality. The second article is titled Semaglutide Misuse in Atypical Anorexia Nervosa – A Case Report. The report presents the case of a patient with a history of an eating disorder who intentionally misused the GLP-1 semaglutide and lost more than 40 pounds in 9 months. The case report is designed to alert clinicians of the importance of reviewing patients’ medical and psychiatric histories, being attuned to patient histories of weight fluctuations, and screening for eating dysregulation when prescribing weight-loss approved medications.

In 1954, Dr Heinz Lehmann published the first clinical article on the use of chlorpromazine. Chlorpromazine was the first synthetic drug used to control states of mania and psychomotor excitement, marking the birth of modern psychopharmacology. Seventy years later, the Journal of Clinical Psychopharmacology is highlighting the anniversary of Dr Lehmann’s publication. The January-February 2024 issue of the journal includes a guest editorial that offers a brief history lesson on Dr Lehmann’s contributions. The authors of the editorial are Drs. Pablo Dutra, Richard Balon, and Antonio E. Nardi. In this podcast, the authors of the editorial are joined by a distinguished group of JCP Editorial Board members to discuss Dr. Lehmann’s research and the many profound ways the research environment has changed in the past 70 years. Along with the authors, the podcast participants are Drs. Carl Salzman, Alan Schatzberg, Leslie Citrome, Matthew Byerly, John Davis, and Anthony Rothschild. Dr Julia Koretski, Digital Editor for JCP, leads the discussion. The guest editorial is published in the January-February 2024 issue of the Journal of Clinical Psychopharmacology, in an article titled "Celebrating 70 Years of the First Publication on Antipsychotic Treatment in North America by Heinz E. Lehmann and Gorman E. Hanrahan: Would Their Methodology Still Be Conceivable?"

We have all seen the television commercials imploring viewers to “ask your doctor” about Drug X, Y, or Z. The authors of a study in the Journal of Clinical Psychopharmacology were interested in finding out how such advertising might affect the prescribing of psychotropic medicines. In this podcast, the authors discuss their research with Dr. Julia A. Koretski, Digital Editor for JCP. The authors of the study are Drs. Bennett Wechsler, Richard Balon, Richard Shader; and Anthony Rothschild. Dr. Balon is an Associate Editor of JCP and Dr. Rothschild is Editor-in-Chief. Dr. Shader is the Founding Editor-in-Chief Emeritus. The researchers surveyed psychiatrists to ask how challenging it was for them to convince patients that a medication was not needed, despite what the advertising might suggest. The results of their survey showed that psychiatrists who were newer to their profession (less than 10 years since they completed training) had a more challenging time than those who were more experienced in changing patients’ minds. In this podcast, the authors discuss how their study came about and the thorny issues raised by the commercial promotion of psychiatric medications. The article titled “Direct-to-Consumer Advertising Survey of Psychiatrists in Massachusetts and Michigan” is published in the January-February 2024 issue of the Journal of Clinical Psychopharmacology.

Replacement therapy is a key tool in the treatment of individuals who abuse opioids. The idea is to replace heroin or morphine with less euphoric and longer-acting substances, such as methadone, under a medication management protocol. The goals of medical-assisted replacement treatment include reducing an individual's craving for abused opioids, preventing medical complications, decreasing criminal behavior and its consequences, and utimately, hopefully, helping the individual become opioid-free. In this podcast, Dr. Richard Balon discusses the potential for replacement therapy for abuse of other types of substances, including cocaine and methamphetamines. In the podcast and in an editorial in the Journal of Clinical Psychopharmacology (JCP), he notes promising but preliminary studies of lisdexamfetamine as a possible replacement agent. Dr. Balon is an Associate Editor of JCP and Professor of Psychiatry at Wayne State University School of Medicine in Detroit, Michigan. In this podcast, he is interviewed by Dr. Julia Koretski, Digital Editor for JCP and a psychiatrist at Mass General Brigham Newton Wellesley Hospital in Newton, Massachusetts. Dr. Balon’s editorial is published in the November–December 2023 issue of the Journal of Clinical Psychopharmacology, in an article titled “The Need for Examining the Role of Psychostimulants in Treatment of Methamphetamine Use/Dependence.”

Clozapine is an important drug in the treatment of schizophrenia, and adherence is generally thought to be as good as, if not better than, other antipsychotics. Nonadherence, however, is difficult to detect and potentially dangerous. Tolerance to the cardiovascular effects of the drug is easily lost; restarting at a “normal” dose can prove fatal after a period of abstinence. Nonadherence also increases the risk of self-harm. In this podcast, Dr. Robert Flanagan, a now-retired clinical scientist at Kings College Hospital in London, discusses his study of nonadherence, as measured by plasma levels of clozapine, in samples submitted to a clozapine therapeutic drug monitoring service from 1993–2017. In thousands of submitted samples, nonadherence was 1.1% for men and 1% for women. Dr. Flanagan discusses both the implications of his research as well its limits. The research is published in the September–October 2023 issue of the Journal of Clinical Psychopharmacology, in an article titled “Assessing Adherence to Clozapine: Practical Considerations.” Dr. Flanagan’s coauthors are Samora Hunter and Stephen J. Obee, also of Kings College Hospital.

Much has been written in recent months regarding the growing use of artificial intelligence (AI) in medicine and the potential benefits and risks of its use. In this podcast, Anthony J. Rothschild, MD, Editor-in-Chief of the Journal of Clinical Psychopharmacology, highlights a paper in the journal by Drs. Jose de Leon and Carlos De Las Cuevas that reports their experiment to see how ChatGPT3 would respond to various questions about clozapine metabolism. The generated text proved to be profoundly unreliable. Dr. Rothschild also discusses his editorial about the journal’s policies regarding use of generative AI by authors and reviewers. Authors must disclose any such use; peer reviewers are prohibited from using AI in conducting their reviews. Dr. Rothschild’s editorial and the commentary by Drs. De Leon and de Las Cuevas both appear in the September–October 2023 issue of the Journal of Clinical Psychopharmacology.

The COVID-19 pandemic and associated public health measures shifted the way people access health care. In this podcast, Dr. Christine Leong, Associate Professor at the University of Manitoba College of Pharmacy, discusses the research she and her colleagues conducted to study the effects of the pandemic on psychotropic medication adherence. The data were drawn from a claims repository that contains information on health service and medication use for almost all Manitoba residents. The study showed improved adherence to most psychotropic medications in the 9 months after public health restrictions were enacted. Patients who were already adherent to their psychotropic medications were less likely to discontinue them during the pandemic. Findings in this study highlight that, although there were concerns about public health measures restricting access to in-person care, access to medications in Manitoba did not seem to be restricted. The article “Adherence to Psychotropic Medication Before and During COVID-19: A Population-Wide Retrospective Observational Study” is published in the July-August 2023 issue of the Journal of Clinical Psychopharmacology.

The July-August 2023 issue of the Journal of Clinical Psychopharmacology features a helpful tutorial written by Drs. Eric G. Smith and Hannah L. Grigorian. Their article is titled “A System for Rapidly Yet Rigorously Evaluating the Quality of Randomized Controlled Trials.” The article should be of particular interest to busy clinicians, researchers, and trainees, who must grapple with the never-ending task of keeping up with the medical literature. In this podcast accompanying the article, Dr. Smith provides an overview of criteria that can be used to assess various aspects of trials, including blinding of participants and study personnel, sample size, follow-up, analysis plans, and effect sizes. Dr. Smith is a psychiatrist and clinical and health services researcher at the VA Bedford Healthcare System, Bedford, Massachusetts, and Assistant Professor of Psychiatry and Population and Quantitative Health Sciences at the University of Massachusetts Chan Medical School. Dr. Grigorian is a psychology research fellow at the VA Bedford Healthcare System.

Hyperammonemia is an adverse effect that poses clinical uncertainty regarding the prescription of valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. In this podcast, clinical pharmacists Michelle Gnrya and Yiu-Ching Jennifer Wong of St. Paul’s Hospital in Vancouver discuss their systematic review that summarizes evidence available regarding VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management. Their review is published in the May-June 2023 issue of the Journal of Clinical Psychopharmacology. The review found various risk factors for this common adverse effect, including concomitant medications, liver injury, and defects in carnitine metabolism. With VPA discontinued, most symptomatic patients returned to baseline mental status with normalized ammonia level. Further studies are required to determine the benefit of routine ammonia level monitoring and to guide the management of VPA-associated hyperammonemia.

Among individuals with schizophrenia, an estimated 50% to 80% have a partial or even total lack of insight into the presence of their mental disorder. This condition, known as anosognosia, has also been observed in people with other diagnoses, such as bipolar disorder, major depression with psychotic features, obsessive-compulsive disorder, and eating disorders. The May-June 2023 issue of the Journal of Clinical Psychopharmacology features two articles on this topic, a commentary by Rachel Streiff, titled “Institutional Neglect of Anosognosia Is a Critical Barrier in the Treatment of Psychosis Related Disorders” and an editorial by Editor-in-Chief Anthony Rothschild, MD, titled “Can Psychopharmacology Do More for Our Patients With Anosognosia?” In this podcast, Ms. Streiff, who as cared for a family member with anosognosia, and Dr. Rothschild discuss their articles with Dr. Julia Koretski, Digital Editor of the journal. The articles and podcast are designed to heighten awareness of the scant research on medication treatments for people with serious mental illness who also experience anosognosia.

For individuals with treatment-resistant depression, ketamine can be an effective fast-acting alternative to conventional antidepressants. It has been hypothesized that it partly exerts its antidepressant effects by modulating the opioid system. In this podcast, Dr. Brandi Quintanilla discusses her study that explored baseline plasma levels of κ-opioid and dynorphin peptides and changes after ketamine infusion. Participants in this randomized trial included individuals with major depressive disorder and healthy volunteers. The results suggest that κ-opioid and dynorphin levels in plasma may not be a major underlying mechanisms of ketamine's therapeutic effects or its dissociative adverse effects. The study, however, may have been underpowered to detect effects, and additional research is needed. Dr. Quintanilla is a psychiatry resident at the University of Texas Health Science Center at Houston and a special research volunteer in the Experimental Therapeutics and Pathophysiology Branch of the National Institute of mental health. The article by Dr. Quintanilla and colleagues is published in the March-April 2023 issue of the Journal of Clinical Psychopharmacology.

Clozapine is a unique antipsychotic with superior efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, approximately 40% to 70% of patients on clozapine continue to experience psychotic symptoms. Nevertheless, there is a concern about how high of a dose to prescribe because adverse effects are related to plasma levels of the drug. In this podcast, Dr. Jan Bogers discusses his research involving stepwise increases in clozapine doses in severely ill, long-stay patients with TRS. The study, conducted at Rivierduinen Mental Health Organization in the Netherlands, concludes that most patients older than 60 years could not tolerate high clozapine levels and so this should not be attempted in older or otherwise physically vulnerable patients. Increasing clozapine levels to approximately 750 ng/mL in middle-aged patients with longstanding TRS may modestly reduce the severity of positive symptoms and improve the response rate. The article appears in the March-April 2023 issue of the Journal of Clinical Psychopharmacology.

Lithium is considered a standard treatment for bipolar disorder, but it remains underprescribed, in part because of its association with kidney dysfunction. In this podcast, Dr. Balwinder Singh discusses an article he and his colleagues published in the January-February 2023 issue of the Journal of Clinical Psychopharmacology on “real-world” clinical practice involving patients with bipolar disorder (BD) and chronic kidney disease (CKD). In their study, patients with BD and CKD who discontinued lithium use after CKD diagnosis had a higher risk for a relapse of their mood disorder as well as a shorter time to the first mood episode, suggesting a need for more thorough discussion before discontinuing lithium after a diagnosis of CKD.

In a commentary published in the Journal of Clinical Psychopharmacology, Dr. Rishab Gupta (Brigham and Women's Hospital/Harvard Medical School) and Dr. Swarndeep Singh (Government Medical College and Hospital, Chandigarh, India) cast a critical eye on India’s regulatory approval for the use of endoxifen for the treatment of manic episodes in patients with bipolar disorder type 1. In their article and in this podcast, they suggest that there are important deficiencies in the research that was used to support the regulatory approval. No other country has approved endoxifen for treating bipolar disorder. They caution that endoxifen should be considered as an option to treat acute mania only after a careful consideration of risks/benefits with the patient and their family and after providing them with a list of alternative medications.

Psychedelics as a potential treatment for depression is an irresistible topic in the mainstream press, but what is the evidence base for their use? In this podcast, psychiatrist and journal Digital Editor Dr. Julia Ann Koretski (of Mass General Brigham Newton-Wellesley Hospital) leads Dr. Ishrat Husain and Dr. Richard Balon through an illuminating discussion of where we stand in clinical trials research and the important limitations of current findings. Dr. Husain is the senior author of “A Critical Appraisal of Evidence on the Efficacy and Safety of Serotonergic Psychedelic Drugs as Emerging Antidepressants: Mind the Evidence Gap” in the November-December 2022 issue of the journal (Volume 42, Issue 6). He is a psychiatrist and researcher at the Center for Addiction and Mental Health in Toronto. Dr. Balon, Associate Editor of the journal and psychiatrist at Wayne State University in Detroit, is author of the accompanying editorial, “Are Magic Mushrooms Really Magic? Psilocybin in the Treatment of Depression.”