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.