The Journal of Clinical Psychopharmacology Podcast

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."