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.

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.