The Journal of Clinical Psychopharmacology Podcast

It has been more than 35 years since clozapine was approved by the FDA for use in the United States. Since then, there have been major advances in pharmacokinetics as well as a substantial accumulation of real-world evidence about its use. In two articles in the May-June 2025 issue of the Journal of Clinical Psychopharmacology, Dr. Jose de Leon and dozens of colleagues call on the FDA to make important changes to the drug's product label to reflect current knowledge about the drug's pharmacology, safety profile, and proper titration. The stakes are high: The medication can be used effectively for treatment-resistant schizophrenia, but there has been concern that it has been underused, resulting in poorer outcomes for patients, including a high rate of suicides. Updating the package insert would help to educate clinicians on its proper use and monitoring for adverse effects. In this podcast, Dr. Julia Ann Koretski, JCP's digital editor, leads a panel discussion on the articles by Dr. de Leon and colleagues. In addition to Dr. de Leon, the other panelists include Dr. Larry Alphs, author of an editorial about the topic, Dr. Richard Balon, a coauthor and JCP Associate Editor, and Dr. Anthony Rothschild, a coauthor and Editor-in-Chief of the journal.   Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part I   Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts.  Part II   Incorporating Real -World Treatment Data Into Clozapine's Product Label

Dr. Jose de Leon speaks with Dr. Julia Ann Koretski, the Journal of Clinical Psychopharmacology's Digital Editor, about practical strategies for clinicians prescribing clozapine. This discussion builds on another podcast episode in which Dr. de Leon and a panel of authors and editors discuss recommendations to the FDA to make important changes to the drug's product label to reflect current knowledge about the drug's pharmacology, safety profile, and proper titration. Dr. de Leon, Professor of Psychiatry at the University of Kentucky College of Medicine, is the lead author of two articles on the topic in the May-June 2025 issue of JCP. In this podcast, Dr. de Leon elaborates on some of the complexities involved in managing clozapine use, given individual differences in clozapine metabolism as well as genetic and ethnic variabilities among groups. He stresses, however, that clozapine is a life-saving tool that can reduce the risk of suicide in people with schizophrenia.       Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part I   Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts.  Part II

Valproic acid is one of the most frequently prescribed mood-stabilizing agents for bipolar disorder, and in some regions of the world, it now competes with lithium as the preferred treatment of choice for bipolar maintenance. There may soon be restrictions on the use of valproic acid, however, because of the risk in neural tube defects and major congenital malformations in children born to mothers and fathers who take it. In this podcast, Dr. Samuel Dotson, from the Northeast Georgia Health System in Gainesville, Georgia, and Emory University in Atlanta, and Dr. Andrew Nierenberg, from the Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General Hospital and Harvard Medical School, discuss the current state of research regarding the benefits and risks of valproic acid in comparison to lithium use. They also discuss the importance of informing patients about their options, noting that lithium use has sometimes been perceived as riskier than it is. Dr. Dotson and Dr. Nierenberg are the authors of a Guest Editorial titled “Growing Concerns Over Valproate Teratogenicity Present an Opportunity for Lithium” in the March-April 2025 issue of The Journal of Clinical Psychopharmacology.

"Designer benzodiazepines" are lab-created chemical derivatives of prescription benzodiazepines. They have not been approved for medical use and there is limited information on their safety and toxicity. More potent than their prescription counterparts, this subset of novel psychoactive substances have been growing in popularity in recent years and pose the potential for dangerous levels of intoxication. In this podcast, Dr. Sahil Munjal, program director of the Atrium Health Wake Forest Baptist psychiatry residency program, leads a discussion of the article “Clinical Management of Designer Benzodiazepine Intoxication: A Systematic Review," with his coauthors Dr. Gregory Noe, Katelyn Li, and Nicholas McDuffee. They provide an overview of designer benzodiazepines in comparison to prescription benzodiazepines and describe the findings from their review of 35 case reports. They discuss clinical presentations of designer benzodiazepine intoxication, common approaches to clinical management, and key takeaways from their review of the literature. Their article appears in the March-April 2025 issue of The Journal of Clinical Psychopharmacology.

Dr. Donald C. Goff, Marvin Stern professor of psychiatry at NYU Grossman School of Medicine, gives an overview of a new combination drug recently approved by the U.S. Food and Drug Administration for the treatment of schizophrenia. It will be marketed as Cobenfy, and its component active ingredients are xanomeline and trospium chloride, representing the first non-dopaminergic antipsychotic approved by the FDA. Dr. Goff briefly explores the decades of pharmaceutical treatment of schizophrenia and lays out the steps toward developing the new combination drug. He offers details on next steps, treatment, more extensive trials of the new drug, related approaches, and refers listeners to his editorial for prescribing information. His guest editorial, “At Last, a Nondopaminergic Agent for the Treatment of Schizophrenia: The Combination of Xanomeline and Trospium (Cobenfy),” is published in the March-April 2025 issue of The Journal of Clinical Psychopharmacology.

Dr. Julia Ann Koretski, a psychiatrist and Digital Editor of the Journal of Clinical Psychopharmacology (JCP), leads a conversation about the guest editorial “Ethics in Psychedelic Science: Promises and Responsibilities” with its author, Dominic Sisti, PhD, a medical ethicist from the Perelman School of Medicine at the University of Pennsylvania, and a JCP podcast panel of Editor-in-Chief Dr. Anthony Rothschild and Associate Editor Dr. Richard Balon. Dr. Sisti provides an overview of recent regulatory actions in this area and summarizes the history of “utopian hype” in the field. The editorial and the podcast discussion detail what elements are required to build a solid ethics infrastructure for psychedelics research and clinical delivery that is free of hype and bias. Sisti advises moving ahead with caution, while noting that “the range of potentially treatable conditions is wide—including PTSD, major depression, anxiety disorder, obsessive compulsive disorder, anorexia nervosa, and substance use disorders.” The guest editorial is published in the January-February 2025 issue of JCP.

About 20% of women experience depression while they are pregnant, and untreated depression has been associated with increased rates of adverse birth outcomes and complications. In this podcast, Julia J. Rucklidge, PhD, of the University of Canterbury in Christchurch, New Zealand, discusses nutrition, pregnancy, and mental health in detail with psychiatrist and Journal of Clinical Psychopharmacology (JCP) Digital Editor Dr. Julia Ann Koretski. Dr. Rucklidge is the senior author of the article “Broad-Spectrum Micronutrients or Antidepressants for Antenatal Depression: Effect on Maternal and Infant Birth Outcomes in an Observational Secondary Analysis of NUTRIMUM,” which is published in the January-February 2025 issue of JCP. The article reports the outcomes of a randomized clinical trial in which women with depressive symptoms were randomized to receive daily micronutrients or a placebo for 12 weeks during their pregnancy. As reported by Dr. Rucklidge and her colleagues, the micronutrients used to alleviate depression in pregnancy may mitigate negative effects of depression on birth outcomes and have more favorable birth outcomes compared with antidepressants.

About 20% of women experience depression while they are pregnant, and untreated depression has been associated with increased rates of adverse birth outcomes and complications. In this podcast, Julia J. Rucklidge, PhD, of the University of Canterbury in Christchurch, New Zealand, discusses nutrition, pregnancy, and mental health in detail with psychiatrist and Journal of Clinical Psychopharmacology (JCP) Digital Editor Dr. Julia Ann Koretski. Dr. Rucklidge is the senior author of the article “Broad-Spectrum Micronutrients or Antidepressants for Antenatal Depression: Effect on Maternal and Infant Birth Outcomes in an Observational Secondary Analysis of NUTRIMUM,” which is published in the January-February 2025 issue of JCP. The article reports the outcomes of a randomized clinical trial in which women with depressive symptoms were randomized to receive daily micronutrients or a placebo for 12 weeks during their pregnancy. As reported by Dr. Rucklidge and her colleagues, the micronutrients used to alleviate depression in pregnancy may mitigate negative effects of depression on birth outcomes and have more favorable birth outcomes compared with antidepressants.

Dr. Julia Ann Koretski, a psychiatrist and Digital Editor of the Journal of Clinical Psychopharmacology (JCP), leads a conversation about the guest editorial “Ethics in Psychedelic Science: Promises and Responsibilities” with its author, Dominic Sisti, PhD, a medical ethicist from the Perelman School of Medicine at the University of Pennsylvania, and a JCP podcast panel of Editor-in-Chief Dr. Anthony Rothschild and Associate Editor Dr. Richard Balon. Dr. Sisti provides an overview of recent regulatory actions in this area and summarizes the history of “utopian hype” in the field. The editorial and the podcast discussion detail what elements are required to build a solid ethics infrastructure for psychedelics research and clinical delivery that is free of hype and bias. Sisti advises moving ahead with caution, while noting that “the range of potentially treatable conditions is wide—including PTSD, major depression, anxiety disorder, obsessive compulsive disorder, anorexia nervosa, and substance use disorders.” The guest editorial is published in the January-February 2025 issue of JCP.

Dr. Julia Ann Koretski, a psychiatrist and Digital Editor of Journal of Clinical Psychopharmacology (JCP), discusses the editorial “Psychopharmacologic Laziness” with its author, Dr. Anthony Rothschild, who is Editor-in-Chief of JCP. He contends that psychotropic medications with well-established efficacy for the treatment of various psychiatric conditions are underprescribed due in part to what he provocatively refers to as prescriber "laziness." Under discussion are lithium, clozapine, and long-acting injectable second-generation antipsychotics. Dr. Rothschild notes that there seems to be a reluctance to treat patients with medications that entail taking blood levels or dosage monitoring, extra patient education, attentiveness to interactions and side effects, or a step outside a comfort zone.   The podcast concludes with suggestions of medication-specific fixes and a rethinking of a psychiatric resident's training to include proficiency in treating with remedies that have a strong evidence base but are viewed as extra work. The editorial is published in the November-December 2024 issue of the Journal of Clinical Psychopharmacology.

According to the US Centers for Disease Control and Prevention, products containing psychoactive compounds such as cannabis or mushroom extracts are increasing in availability though they may have undisclosed ingredients, contaminants, and adulterants. Elisa Nguyen, and Drs. Abraham Qavi and Minh-Ha Tran, authors of the letter to the editor “Health Alert: Microdose Products Leading to Acute Illness and Hospitalizations Across the United States” offer general information on personal use availability of Schedule 1 controlled substances such as psilocybin, cannabis, and lysergic acid diethylamide. The letter details recent occurrences of illness, hospitalization, and deaths. Outside of the confines of carefully conducted clinical trials, consumers place themselves at risk of adverse effects through consumption of unregulated products available in nearly half of the United States. The letter to the editor is published in the November-December 2024 issue of the Journal of Clinical Psychopharmacology.

This podcast features Dr. Chadi Calarge, a child psychiatrist at Baylor College of Medicine and, for over 20 years, a researcher focused on long-term psychiatric medication safety with regard to height growth and metabolic abnormalities. He gives an overview of past and forward-looking research questions related to growth, growth hormones, and such drugs as selective serotonin reuptake inhibitors and stimulants. He discusses the journal article, “Fluoxetine and Sertraline Inhibit Height Growth and Growth Hormone Signaling During Puberty,” which was written with 10 co-authors and is published in the November-December 2024 issue of the Journal of Clinical Psychopharmacology.

Ketamine and esketamine represent significant advancements for patients with treatment-resistant depression. Their rapid action provides much needed relief for patients who do not respond to traditional antidepressants. Their use, however, introduces challenges that necessitate ongoing research and careful consideration to maximize their potential, which Dr. Balwinder Singh, MD, MS, details in this podcast. Important challenges include unregulated or poorly monitored use of these potentially addictive products and risks related to the creation of compounded ketamine options. Dr. Singh is an assistant professor of psychiatry at the Mayo Clinic in Rochester, Minnesota, and the medical director of the mood program at the Mayo Clinic Depression Center. His guest editorial, titled “Ketamine and Esketamine for Depression in Daily Practice: Opportunities and Challenges,” is published in the September-October 2024 issue of the Journal of Clinical Psychopharmacology.

The symptoms of irritability associated with autism spectrum disorder (ASD) include aggression, tantrums, self-injury, and disruption. Propranolol, a beta-blocker, has accumulated much anecdotal evidence as a promising option for symptoms of these disorders, but well-designed studies are rare. Dr. Eric London is the lead author of the article “High-dose propranolol for severe and chronic aggression in autism spectrum disorder: A pilot, double-blind, placebo-controlled, randomized crossover study,” which is published in the September-October 2024 issue of the Journal of Clinical Psychopharmacology. The article describes its effectiveness in decreasing aggression in individuals with ASD. As this was a small study, a larger clinical trial is needed. Dr. London is director of Autism Treatment Research at the New York State Institute for Basic Research. In this podcast, he offers extensive background on treatment challenges and the difficult core symptoms of ASD.

It has been hypothesized that alterations in the gut microbiota may play a part in the pathophysiology of schizophrenia, including immune system dysfunction. Preliminary evidence suggests that people with schizophrenia have decreased relative abundance of butyrate-producing bacteria in the gut microbiota. Butyrate plays a critical role in maintaining the integrity of the gut-blood barrier and has anti-inflammatory effects. A proof-of-concept study published in the Journal of Clinical Psychopharmacology was designed to assess whether treatment with an oligofructose-enriched inulin prebiotic could increase the production of butyrate. The study demonstrated that the treatment selectively increased the level of plasma butyrate in people with schizophrenia. The article, titled “Prebiotic Treatment in People with Schizophrenia,” appears in the September-October 2024 issue of the journal. The podcast provides a “somewhat more detailed background rationale for the study” than in the article, according to Dr. Robert W. Buchanan, professor of psychiatry at the Maryland Psychiatric Research Center in Baltimore, first author of the paper, who discusses the results of this study and ongoing research in a larger cohort.

Psychotic bipolar depression (PBD) is a prevalent yet understudied psychiatric illness with no specific guidelines or Food and Drug Administration-approved medications for its treatment. Recent studies suggest that some antipsychotics and mood stabilizers may be effective in managing bipolar depression; however, their effectiveness for PBD remains unclear. With an urgent need for more focused research for managing PBD, several authors conducted a literature review to piece together existing literature on the topic.   In this podcast, Dr. Julia Ann Koretski, Digital Editor of the Journal of Clinical Psychopharmacology (JCP), discusses the review with two of its authors, Dr. Maité Cintrón Pastrana and Dr. Anthony Rothschild, who is Editor-in-Chief of the Journal of Clinical Psychopharmacology. Both authors are from the University of Massachusetts Chan Medical School. A third author, Jessica C. Irizarry Flores, is from the Ponce Health Science University Medical School in Puerto Rico.   The article appears in the July/August 2024 issue of the journal.

There are two distinct and unrelated definitions of the word “floxing.” In this podcast, the author of an editorial in the July-August 2024 issue of the Journal of Clinical Psychopharmacology discusses both, while providing an interesting lesson about potential drug-drug interactions that psychiatrists should be mindful of.   The author is Dr. Richard Shader, who is Founding Editor-in-Chief Emeritus of the Journal of Clinical Psychopharmacology. Dr. Shader describes the two definitions in a conversation with Dr. Julia Ann Koretski, a psychiatrist at Mass General Brigham Newton-Wellesley Hospital and Digital Editor of Journal of Clinical Psychopharmacology,   In recent decades in genetics and biology, floxing has meant to insert or sandwich a specific DNA sequence in a targeted gene. The current lay or street language term is, however, the topic of the podcast. Here, floxing refers to serious side effects attributed to the use of fluoroquinolone antibiotics. The Food and Drug Administration (FDA) refers to these effects as fluoroquinolone-associated disability or FQAD. The podcast focuses on those disabilities and the need for prescribers to guard against drug-drug interactions of the widely used antibiotic ciprofloxacin with widely prescribed psychotropic medications including clozapine, duloxetine, and fluvoxamine. Dr. Shader calls for case studies to demonstrate toxicity and to ferret out causality. Clinicians should direct instances of interaction to FDA's reporting portal www.fda.gov/medwatch.

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.”

In this podcast, Dr. Jonathan Leung discusses the article, “The Modernization of Clozapine: A Recapitulation of the Past in the United States and the View Forward,” published with several colleagues in the November-December 2022 issue of the Journal of Clinical Psychopharmacology (Volume 42, Issue 6). Dr. Leung, lead author of the review article, is a psychiatric pharmacist at the Mayo Clinic in Rochester, MN, and faculty member at the Mayo Clinic College of Medicine. Clozapine is a unique life-saving drug for treatment-resistant schizophrenia and reduction in risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder, but it is underused in the United States despite its established efficacy. Clozapine's benefits for reduction of suicidality may extend to other uses as well, although more rigorous studies are needed. The article and podcast discuss the history of FDA approval for clozapine, hematologic monitoring requirements that have been viewed as cumbersome, as well as other barriers related to clozapine use.

In small-scale studies, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder has shown some promise, but exploratory analyses have suggested that recent use of selective serotonin reuptake inhibitors (SSRIs) can dampen the efficacy of this novel therapy. In this podcast, Dr. Collin M. Price, a psychiatric resident at UCLA, and Dr. Allison Feduccia, a neuropharmacologist and CEO of a company that curates CME courses on psychedelics, discuss their new article in the Journal of Clinical Psychopharmacology that provides a selective review of the literature in the basic and clinical neurosciences relevant to the interaction of SSRIs and MDMA. They suggest that there is an urgent need for future work dedicated to addressing this important clinical topic. Their article is published in the September-October 2022 issue of the journal.

In this podcast, Dr. Melvin McInnis discusses lithium toxicity in individuals with bipolar disorder who were infected by the SARS-CoV-2 virus. Lithium is an effective long-term management strategy for treating bipolar disorder, but because acute kidney damage can be a complication of COVID-19, the body's ability to process lithium may be affected. Based on his case report study, coauthored by Dr. Anastasia Yocum and published in the September-October 2022 issue of the Journal of Clinical Psychopharmacology, Dr. McInnis urges proactive monitoring for signs of diminished kidney functions to avoid levels of toxicity, especially during the pandemic.

Panic disorder is a common psychiatric disorder, with generally effective pharmacologic treatments for most patients. However, a subset of patients do not respond,  and roughly 25% of patients have adverse effects. In this podcast, based on his guest editorial published in the September-October 2022 issue of the Journal of Clinical Psychopharmacology, Dr. Antonio Nardi makes the case that the next era of treatments may be inhibitor specific. Because of the amygdala's essential role in the control of anxiety responses, Dr. Nardi suggests that it may be the key to developing such therapies. While acknowledging that his editorial focuses on selective molecules for α2/3-GABAAR, Nardi expresses hope that the two classes of GABAkines in clinical development, studied in conjunction with models of carbon dioxide inhalation in healthy volunteers, might represent the beginning of a new era in treatment for panic disorder.

A recently published book provides sharp criticism of the modern era of clinical psychopharmacology, questioning the validity of psychiatric diagnoses and the effectiveness of psychopharmacologic treatments. In this podcast, Dr. Anthony J. Rothschild, Editor-in-Chief of the Journal of Clinical Psychopharmacology, offers his perspective on the book, The Rise and Fall of the Age of Psychopharmacology. The book “ignores the fact that many people with serious psychiatric disorders have had their lives dramatically improved by psychotropic medications,” Dr. Rothschild says, noting that he vehemently disagrees with how the book's author characterizes the profession. The podcast accompanies Dr. Rothschild's editorial in the July-August 2022 issue of the journal.

  Clozapine is often prescribed for patients with treatment-resistant schizophrenia, but its use is sometimes discontinued if it is suspected of inducing neutropenia. In this podcast, author Laurent Béchard discusses a consecutive case series published in the July-August 2022 issue of the Journal of Clinical Psychopharmacology assessing the continuation or reintroduction of this drug despite a neutropenia episode. In addition to suggesting further research to better define severe vs. moderate cases, Dr. Béchard proposes the use of pharmacovigilance tools to assess possible causes of neutropenia so clinicians can better determine if this highly effective antipsychotic should remain part of a patient's treatment plan.

In this podcast, Editor-in-Chief Anthony Rothschild discusses his editorial in the May-June 2022 issue about the use of antipsychotic medications for treatment of nonpsychotic patients. With four drugs approved by the FDA for use as augmentation for the treatment of nonpsychotic depression, and possibly a fifth soon, he advocates for more longitudinal studies to better understand the potential risks vs. benefits to this practice. While citing previous similar treatment approaches in the history of psychopharmacology, Dr. Rothschild advocates that until potentially serious adverse effects can be ruled out, the prescription of antipsychotic medications to nonpsychotic patients should be limited to those who are resistant to all other treatments.

The use of the combination of stimulants and antipsychotic medications is increasing in pediatric patients who suffer from Attention Hyperactivity Disorder (ADHD). In this podcast, Dr. Mohamed Mohamoud discusses how this combination may result in acute hyperkinetic movement disorder in children. Using the FDA Adverse Event Reporting System database, Dr. Mohamoud and his colleagues conducted a case series analysis and identified 36 instances where a pharmacodynamic drug-drug interaction may have resulted in the disorder. Their report is published in the May/June 2022 issue of the Journal of Clinical Psychopharmacology. Prescribing information has recently been updated and this podcast discusses the data upon which that information was changed. Dr. Mohamoud is being interviewed by FDA press officer Charlie Kohler.

Drs. Steve Dubovsky and Dori Marshall discuss their article reviewing the potential of calcium channel blockers for the treatment of mood disorders, an area of research that the authors assert has received too little attention. Their article, titled Calcium Channel Antagonists for Mood Disorders, appears in the March-April 2022 issue of the Journal of Clinical Psychopharmacology.

“Polypharmacy,” the simultaneous use of multiple medications, has been linked to an increased risk of treatment complications. An article in the March-April 2022 issue of the Journal of Clinical Psychopharmacology takes a systematic look at research studies that have tested interventions to optimize polypharmacy in psychiatric treatment and nursing homes. Improvement of drug-related outcomes can be achieved by interventions such as individualized medication review and educational approaches. Changes in clinical outcomes, however, are often not substantial. Drs. Philip Stötzner and Eva Brandl, two of the authors of the systematic review, discuss their findings and avenues for future research.

How can we improve psychopharmacology practice? This podcast features a lively discussion among the authors of two articles in the January-February 2022 issue of the Journal of Clinical Psychopharmacology in which they address that important topic. The participants discuss some weaknesses in current models of psychopharmacology training as well as the challenges clinicians face in keeping up with medication advances.

A large observational study from researchers at Washington University in St. Louis found an elevated risk of breast cancer in women who take some types of antipsychotic drugs – specifically, drugs that raise levels of the hormone prolactin. In this podcast, Dr. Tahir Rahman, lead author of the study, discusses the findings and their implications for patient care.

In the effort to prevent relapse in patients who have experienced depressive episodes, it has been common practice to have them continue long-term on antidepressant medications, including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). In this author podcast, Giovanni A. Fava discusses his guest editorial that challenges that custom and suggests alternative approaches for preventing relapse. Dr. Fava's Guest Editorial is published in the November-December 2021 issue of the Journal of Clinical Psychopharmacology.

The link between substance abuse, impulsivity, and violence in psychotic patients remains unclear. In this author podcast, Gabriella Gobbi, MD, PhD, and Stefano Comai, PhD, discuss their study, which was designed to assess whether cannabis use disorder is associated with violent and/or psychotic behavior in patients who are hospitalized in a high-security hospital. The findings show that cannabis and alcohol are often abused (by themselves or together) by psychotic patients with a propensity for violence, but only alcohol is associated with impulsive and violent behavior. The article is published in the November-December 2021 issue of the Journal of Clinical Psychopharmacology.