PsyQ: Journal Club

Public perception often creates a direct and frightening link between mental illness and violence, but what does the evidence actually show? In this episode of PsyQ, we challenge common assumptions by exploring the complex reality of violence risk assessment. Using a case study of a patient making homicidal threats, we break down the crucial difference between static risk factors (like history and personality) and dynamic risk factors (like substance use and situational stressors) that clinicians can actually influence. We'll walk through the structured, evidence-based frameworks, including the "Five D's" of management, that guide professionals in high-stakes situations where the threat of violence may not stem from a treatable acute psychiatric illness. This is a deep dive into moving beyond intuition to a defensible, nuanced approach for every clinician facing this profound challenge.

Source:

Saxton, A., Resnick, P., & Noffsinger, S. (2018). Chief complaint: Homicidal. Assessing violence risk. Current Psychiatry, 17(5), 26–28, 30–32, 34, 55.

In this episode, we tackle one of psychiatry's most complex challenges: Obsessive-Compulsive Disorder. We begin with a deep dive into the landmark 2005 Foa et al. trial, a methodologically rigorous study that definitively established the superior efficacy of intensive Exposure and Ritual Prevention (ERP) over potent pharmacotherapy with clomipramine. Using this foundational evidence, we build a practical, stepped-care algorithm for managing treatment-resistant OCD (TR-OCD). The discussion navigates the nuances of maximizing first-line SRIs, evidence-based augmentation with antipsychotics and glutamatergic agents, and the role of advanced neuromodulation techniques like TMS and Deep Brain Stimulation. We'll synthesize these disparate treatments through the unifying neurobiological lens of the Cortico-Striato-Thalamo-Cortical (CSTC) circuit, providing trainees with a cohesive framework for treating their most challenging OCD patients.

Article:Foa, E. B., Liebowitz, M. R., Kozak, M. J., Davies, S., Campeas, R., Franklin, M. E., ... & Tu, X. (2005). Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder. American Journal of Psychiatry, 162(1), 151-161.

We dive into two landmark studies that have dramatically expanded the genetic map of bipolar disorder, identifying nearly 300 risk loci from over 150,000 patients. We explore the game-changing discovery of the AKAP11 gene, which provides a direct molecular link to lithium's mechanism, and unpack the complex genetic architecture that both unites and separates bipolar disorder from schizophrenia and its own subtypes. Finally, we translate these complex findings into clinical practice, discussing the current role of pharmacogenetic testing, how to counsel families about genetic risk, and what the future of precision psychiatry for bipolar disorder might look like.

Sources:

Mullins, N. et al. (2021). Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics, 53, 817-829.

O'Connell, K.S. et al. (2025). Genomics yields biological and phenotypic insights into bipolar disorder. Nature, 639, 968-975.

Treating adolescent depression is one of the most significant challenges in mental health, a landscape complicated by the FDA's black box warning about antidepressant-associated suicide risk. This episode dives deep into the landmark Treatment for Adolescents With Depression Study (TADS), the large-scale, NIMH-funded trial designed to bring clarity to this complex issue. We explore the study's crucial findings, from the "horse race" between fluoxetine, CBT, and their combination, to the critical data on safety and suicidality. Join us as we unpack why combination therapy emerged as a superior strategy, how CBT acts as a protective shield, and what these results mean for clinicians, families, and teens making real-world treatment decisions today.

Reference: The TADS Team. (2007). The Treatment for Adolescents With Depression Study (TADS): Long-term Effectiveness and Safety Outcomes. Archives of General Psychiatry, 64(10), 1132–1144.

In this episode we explore the landmark MTA study, unraveling its insights into ADHD treatment from childhood to adulthood. We'll cover the initial trial's findings on medication and combined therapy, then trace how these effects evolved, highlighting the surprising persistence of impairment compared to peers and the nuanced impact of long-term stimulant use on height versus symptoms. This episode offers essential clinical pearls, emphasizing individualized, quality care, the chronic nature of ADHD, and the importance of addressing comorbidities.

Studies Referenced in this Episode:

The MTA at 8 Years: Prospective Follow-Up of Children Treated for Combined Type ADHD in a Multisite Study

Multimodal Interventions Are More Effective in Improving Core Symptoms in Children With ADHD

A 14-Month Randomized Clinical Trial of Treatment Strategies for Attention-Deficit/Hyperactivity Disorder

Young adult outcomes in the follow-up of the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder: symptom persistence, source discrepancy and height Suppression

This episode, we delve into the rapidly evolving landscape of GLP-1 receptor agonists in psychiatry. We'll critically appraise Hendershot et al.'s (2025) JAMA Psychiatry study on once-weekly semaglutide for Alcohol Use Disorder, examining its efficacy in reducing alcohol consumption and craving in a randomized clinical trial. We then broaden our scope with Pierret et al.'s (2025) systematic review and meta-analysis in JAMA Psychiatry, which assesses the psychiatric safety profile and quality of life outcomes associated with GLP-1 RA treatment. Finally, we integrate insights from the Carlat Psychiatry Report (Aiken & Liebers, 2025) on "New Weight Loss Drugs in Psychiatry," exploring mechanisms, potential applications for antipsychotic-induced weight gain, binge eating disorder, mood, and cognition, alongside crucial risk considerations. Join us as we synthesize these findings and discuss their clinical implications for psychiatric practice.

Sources:

Hendershot CS, et al. (2025). Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry.

Pierret ACS, et al. (2025). Glucagon-Like Peptide 1 Receptor Agonists and Mental Health: A Systematic Review and Meta-Analysis. JAMA Psychiatry.

Aiken C & Liebers D. (2025). New Weight Loss Drugs in Psychiatry. The Carlat Psychiatry Report.

This two-part episode takes a comprehensive look at clozapine, one of psychiatry's most impactful and complex medications. The two parts are (1) context, and (2) clinical pearls. We explore its challenging history, landmark clinical trials, unique pharmacology, practical prescribing guidelines, and the recent evolution of its regulatory oversight. Essential listening for psychiatry trainees and practicing clinicians.

Sources used:

1. Kane (1988). Clozapine for the Treatment-Resistant Schizophrenic: A Double-blind Comparison With Chlorpromazine. Arch Gen Psychiatry

2. Hippius (1999). A Historical Perspective of Clozapine. J Clin Psychiatry

3. Clozapine—serious adverse effects and clinical management. Chapter 12 in Antidotes to Toxins and Drugs.

4. FDA. Feb 2025 Information on Clozapine. FDA.gov.

5. Schneider-Thoma (2025). Efficacy of clozapine versus second-generation antipsychotics in people with treatment-resistant schizophrenia: a systematic review and individual patient data meta-analysis. Lancet Psychiatry

This week on PsyQ, we dive into the controversial practice of co-administering parenteral olanzapine and benzodiazepines for agitation. We revisit the 2005 FDA warning prompted by post-marketing reports (Marder et al., 2010) and critically examine the causality behind the reported fatalities. Contrasting this, we explore subsequent research, including observational studies (Williams, 2018; Wilson et al., 2012), an RCT using IV formulations (Chan et al., 2013), and a large recent retrospective study (Cole et al., 2024), which suggest the combination may be safer than the initial warning implied, finding no significant increase in severe cardiorespiratory events like intubation compared to olanzapine alone, even within 60 minutes and in patients with alcohol intoxication. We discuss the differing regulatory stances (FDA vs. EMA), practical implications, patient selection (caution with respiratory compromise/alcohol), and how this evolving evidence landscape might impact clinical decision-making in managing acute agitation.

Key Studies Discussed:

Marder SR et al. (2010): Original post-marketing case reports leading to the warning. J Clin Psychiatry.

Williams AM (2018): MUE finding no SAEs with IM olanzapine + lorazepam. Ment Health Clin.

Wilson MP et al. (2012): Compared olanzapine+benzo vs haloperidol+benzo; highlighted alcohol risk. J Emerg Med.

Chan EW et al. (2013): RCT showing safety of IV olanzapine + midazolam. Ann Emerg Med.

Cole JB et al. (2024): Large retrospective study finding no difference in intubation/hypoxia/hypotension rates between olanzapine+benzo vs olanzapine x2. Ann Emerg Med.

Carlat Psychiatry Report Summary: Overview and clinical take on the evidence.

This podcast is AI generated with human input and review, however there may be errors, so for the most accurate and up to date information, please consult the primary sources.

This is an AI generated podcast with human review. This episode provides guidance on the prophylactic management of bipolar disorder during pregnancy and postpartum, referencing the Uguz et al. (2023) review. We cover the high relapse risks (particularly postpartum), the core dilemma of balancing maternal health with infant safety, and evidence-based medication choices. Key takeaways include the importance of individualized planning, avoiding high-risk drugs like valproate, adjusting doses dynamically, and integrating medication with crucial psychosocial supports and sleep strategies.

Notes: pronunciation issues with medication names and "Bipolar 1" is said as "Bipolar i", content has been reviewed for accuracy.

Article: https://pubmed.ncbi.nlm.nih.gov/37683233/