The Journal of Clinical Psychopharmacology Podcast The Journal of Clinical Psychopharmacology

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.