As interest grows in the therapeutic potential of ketogenic diets for bipolar disorder, careful attention must be given to drug-diet interactions. Overlapping mechanisms between therapeutic ketosis and mood-stabilizing agents may offer opportunities for synergistic effects, but may also introduce risks related to altered pharmacokinetics, pharmacodynamics, and additive toxicities. In this podcast, Dina N. Ali, MD, and Jonathan Leung, PharmD, discuss the complex picture of trying to optimize treatment outcomes while many research questions are yet to be answered. Ali and Leung are authors of the commentary, "Diet Drug Interactions: Achieving and Maintaining Ketosis As Adjunct to Psychotropic Polypharmacotherapy," which is published in the November-December 2025 issue of the Journal of Clinical Psychopharmacology.

The other contributing authors are Mark A. Frye, MD; Iain H. Campbell, PhD; Matej Markota, MD; Mikaela M. Hofer, PharmD, and Heather Standorf, PharmD. doi: 10.1097/JCP.0000000000002074

In this podcast, Nicolas Badre, MD, and Eric Geier, MD, PhD, discuss their article, "Anticholinergic Equivalence in Psychotropic Medications: A Guide for Psychiatrists," which is published in the November-December 2025 issue of the Journal of Clinical Psychopharmacology.

Anticholinergic side effects from psychotropic medications are common and can lead to significant adverse events, including cognitive impairment and falls, particularly in vulnerable populations like the elderly. The cumulative anticholinergic burden from multiple medications is a critical concern associated with poorer clinical outcomes. Quantifying this burden is essential for safer prescribing. For their article, they developed a table to provide a practical tool for psychiatrists to quantify and compare the anticholinergic potential of psychotropic medications.

doi: 10.1097/JCP.0000000000002073

A presidential executive order early this year directed federal departments and agencies to address the issue of chronic disease in the United States, including "the prevalence of and threat posed by the prescription of selective serotonin reuptake inhibitors (SSRIs)," with a particular focus on youth.

In this podcast, Dr. Jeffrey R. Strawn discusses his editorial, "Fact Versus Fear: Antidepressants in Children and Adolescents," which is published in the September-October 2025 issue of the Journal of Clinical Psychopharmacology.

In the editorial, Dr. Strawn and his coauthor, Dr. John T. Walkup, write that the framing of the issue in the executive order risks reinforcing stigma and diminishing trust in evidence-based pediatric mental health care. The editorial summarizes the evidence supporting the efficacy, safety, and tolerability of SSRIs in youth and contextualizes these findings within a discussion of the risk of withholding potentially effective treatments due to stigma and misinformation. The editorial is published in the September-October 2025 issue of the Journal of Clinical Psychopharmacology.

doi: 10.1097/JCP.0000000000002054

Many patients view the return of "positive mental health" (PMH) to be their most important goal of treatment for major depressive disorder (MDD). However, few studies have systematically measured PMH or prospectively examined the added value of considering PMH as a treatment predictor of outcomes.

In this podcast, Dr. Somaia Mohamed discusses her article, "How Does Positive Mental Health Affect Next-Step Treatment Outcomes in Treatment-Resistant Depression? A VAST-D Report." Dr. Mohamed and her coauthors found that high PMH scores at baseline were associated with a greater chance of remission.

The article is published in the September-October 2025 issue of the Journal of Clinical Psychopharmacology. In addition to Dr. Mohamed, the other authors are Sidney Zisook, Gary R. Johnson, and Beata Planeta.

doi: 10.1097/JCP.0000000000002051

Antidepressants are in widespread use, but there is considerable variability in how patients respond, with some seeing substantial improvement while others respond only partially or not at all.

In this podcast, Dr. Antonio E. Nardi discusses the many factors that underlie response rates, including psychological factors, personality traits, and medication adherence. There are also some mood conditions such as demoralization that may seem to resemble depression but do not meet all the clinical criteria. Recognizing these different emotional states is crucial for both individuals and clinicians in the treatment of low mood disorders.

Dr. Nardi, along with Drs. Richard I. Shader, Richard Balon, Anthony J. Rothschild, and Larissa Junkes, are the authors of an editorial titled, " 'I am depressed': The many meanings that may underlie variability in response to antidepressants." The editorial is published in the September-October 2025 issue of the Journal of Clinical Psychopharmacology.

doi: 10.1097/JCP.0000000000002053

Examining a patient's family history of medication response is a commonly used method to guide physicians in treatment selection. Though it is widely recommended, there are no published reviews that assess the validity of this approach when treating patients with affective disorders. In this podcast, authors Jeffrey J. Rakofsky, Michael J. Lucido, and Boadie W. Dunlop of the Department of Psychiatry and Behavioral Sciences at Emory University discuss their article, "A Systematic Review to Determine if Family History of Response to Medication Predicts Outcome in Mood Disorders," which is published in the July-August 2025 issue of the Journal of Clinical Psychopharmacology. In their analysis, the evidence supporting using family history is weak and should be considered as just one piece of the puzzle that should not override other considerations. doi: 10.1097/JCP.0000000000002011

There is considerable evidence that marketing affects physician prescribing practices, even though physicians themselves may not feel that they are influenced. In a thought-provoking editorial, Dr. Jeffrey A. Mattes explores how e-prescribing systems may be one pathway through which pharmaceutical messaging may shape prescribing behavior. In this podcast, Dr. Mattes discusses his editorial, "How Does Drug Company Marketing Affect Physician Prescribing?" which is published in the July-August 2025 issue of the Journal of Clinical Psychopharmacology. doi: 10.1097/JCP.0000000000002030

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

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.