PsyQ: Journal Club

In this episode of PsyQ, we perform a forensic analysis of the landmark OPTIMUM trial, a study that fundamentally reshapes the treatment algorithm for resistant depression in older adults. We dissect the head-to-head battle between switching antidepressants versus augmentation, revealing why aripiprazole claims the crown for efficacy while exposing a counterintuitive and critical safety signal regarding bupropion-induced falls. Beyond the clinical pearls, we guide you through the statistical machinery under the hood—specifically how the Benjamini-Hochberg procedure saved the study's primary finding—and introduce the "Rule of Three," a data-driven threshold that suggests exactly when clinicians should stop cycling medi...

In this episode, we break down a major longitudinal synthesis of seven North American cohort studies following children with ADHD into adulthood over 10–30 years. The data are striking: while full diagnostic persistence varies, the majority of individuals continue to experience clinically meaningful symptoms and impairment well into adult life. Persistent ADHD is associated with lower educational attainment, unemployment, financial instability, higher rates of mood and substance use disorders, antisocial behavior, driving risk, emergency medical utilization, and even reduced life expectancy. Comorbid disruptive behavior disorders emerge as the strongest predictors of adverse adult outcomes, while internalizing symptoms in females drive el...

In this episode, we dissect a landmark 2022 randomized controlled trial published in the American Journal of Psychiatrythat challenges the traditional "daily dose" paradigm for treating Alcohol Use Disorder (AUD). We review the efficacy of targeted, event-driven oral naltrexone—taken only in anticipation of heavy drinking or cravings—specifically for sexual and gender minority (SGM) men with mild-to-moderate AUD.

We analyze how this "chemical shield" approach yielded a Number Needed to Treat (NNT) of just 2 to prevent a binge-drinking day , significantly reduced overall consumption volume , and demonstrated sustained therapeutic effects six months post-treatment through likely pharmacological exti...

In this episode, we unpack the psychiatric relevance of the ketogenic diet through the lens of a recent and compelling systematic review and meta-analysis from JAMA Psychiatry. Join us as we explore how ketogenic diets may modulate mood, inflammation, neurotransmission, and energy metabolism—domains increasingly central to the practice of modern psychiatry. We’ll break down what the evidence says (and doesn’t say) about its utility in depression and anxiety, clinical pearls for implementation, safety considerations, and which patients may benefit most. Perfect for psychiatry residents, faculty, and anyone curious about nutritional psychiatry with a rigorous, translational focus.

Antidepressant discontinuation is one of the most contentious topics in psychiatry, fueling both patient fear and clinical uncertainty. But what does the highest quality, placebo-controlled evidence actually say? In this episode, we dive deep into the 2025 JAMA Psychiatry systematic review and meta-analysis by Kalfas et al. that re-examines the incidence and nature of discontinuation symptoms. We break down the study's striking headline finding—that stopping an antidepressant, on average, results in just one additional symptom compared to stopping placebo, a number below the threshold for clinically significant discontinuation syndrome. We discuss which symptoms, like dizziness , are pharmacologically real versus th...

In this episode of PsyQ, our psych journal club dives deep into the Bush–Francis Catatonia Rating Scale (BFCRS), guided by the 2022 BFCRS Training Manual and its original 1996 validation study. We walk through each of the 23 items in the scale, clarifying their definitions, how to observe and score them, and the key differentiations between overlapping signs such as mutism, withdrawal, and negativism. From subtle signs like mitgehen and ambitendency to high-risk indicators of malignant catatonia, this conversation aims to strengthen clinical fluency and improve bedside assessment. Whether you’re a trainee learning to recognize catatonia or a seasoned clinician refi...

In this week’s episode of PsyQ, we break down the American Journal of Psychiatry review “Ketamine for Depression, but at What Cost?” by Li and colleagues. Here we explore the balance between ketamine’s rapid antidepressant benefits and its potential neurotoxic risks. We’ll discuss what animal and human studies reveal about dose, frequency, and safety, why FDA-regulated esketamine appears cognitively safe while off-label ketamine use raises concern, and how clinicians can responsibly navigate this evolving treatment landscape.

Reference: Li SW, Kumpf KT, Urrutia J, Krystal JH, Sanacora G, Wilkinson ST. Ketamine for Depression, but at Wha...

In this episode, we take a clinical look at psychedelic-assisted therapy — what it is, how it works, and where it’s headed. We cover MDMA for PTSD and psilocybin for depression, break down the science behind how these drugs work with therapy, and review key trial data, safety concerns, and how psychiatrists may soon integrate these treatments into practice. This episode delivers clear takeaways, clinical pearls, and a balanced view on this rapidly evolving field.

In this episode of PsyQ, we take a critical look at the evolution of major depression treatment over the past two decades. We start with the foundational Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, a study that has shaped clinical practice for years with its widely cited ~70% cumulative remission rate. However, we then dive deep into a startling 2023 re-analysis that challenges this cornerstone of psychopharmacology, revealing a cumulative remission rate closer to 35% when the original study's protocol is strictly followed. This critical re-evaluation serves as a springboard to explore the future, as we discuss a 2024 review on...

In this episode, we break down BrainsWay’s 6-day accelerated Deep TMS for major depression—how its iTBS, 5-sessions-per-day schedule compresses a month of treatment into 6 days with non-inferior outcomes to standard daily TMS—then stack it up against conventional 4–6 week TMS and Stanford’s SAINT (the 5-day, 50-session, MRI-guided protocol boasting rapid, high remission rates). We’ll walk through patient flow (session length, spacing, acute + maintenance phases), efficacy (response/remission and time-to-relief), safety (mostly transient scalp discomfort/headache; no new safety signals), practicalities (staffing and workflow for multi-session days), and the real-world stuff clinicians care about—FDA status (BrainsWay’s ac...

In this episode, we dissect the alarming 75.6% rise in private equity (PE) ownership of US psychiatric hospitals and unpack the central paradox from a landmark 2025 JAMA Psychiatry study: how do these facilities operate with significantly fewer nurses and social workers, yet report better outcomes on official quality metrics like restraint use and readmissions? We deconstruct this quality illusion, revealing how self-reported data, administrative gaming, and the strategic "cream-skimming" of less-ill patients can mask the erosion of care. Drawing stark warnings from the devastating impact of PE in other sectors—where the model is linked to increased patient mortality—we prov...

In this week’s episode of PsyQ, we explore psychiatry’s role in decreasing violence in America. While mental illness is often blamed for violent acts, research shows it accounts for only a small fraction of overall violence. Instead, substance use, social stressors, and access to firearms are far more influential. We discuss how psychiatrists can assess and mitigate risk, the limits of violence prediction, and how tools like red flag laws, crisis intervention teams, and public policy reforms can save lives. The episode highlights practical pearls for clinicians and trainees: focus on modifiable risks, document and act decisively when...

In this episode we’ll orient listeners to catatonia’s core features and standard pathways (lorazepam → ECT), then pivot to emerging third-line options when Ativan is ineffective and ECT isn’t feasible. Using a recent systematic review and a bipolar-catatonia case report as anchors, we’ll cover why NMDA antagonism makes mechanistic sense, dosing patterns (most reports used 0.5 mg/kg IV over ~40 min, often as a short series), and what the aggregate signals show: ~80% response and ~44% remission across published cases, with no reported worsening of catatonia or psychosis and only one discontinuation for dissociation. We’ll also highlight real-world scenarios wh...

How should psychiatrists respond when patients use racist language or refuse care based on a clinician’s identity? In this episode, we translate the NEJM five-factor framework into psychiatry’s day-to-day reality—balancing EMTALA obligations and patient autonomy with Title VII protections and clinician well-being—and turn it into practical playbooks for the ED, inpatient units, and clinic. We cover rapid triage in emergencies, capacity and intent assessment (illness-driven vs. bigotry), boundary-setting scripts, when (and when not) to accommodate, safe transfer options, documentation, debriefing, and institution-level policies (codes of conduct, bystander support, reporting pathways). Pearls focus on protecting staff while en...

In this episode, we explore the role of olanzapine/samidorphan (OLZ/SAM) in the treatment of schizophrenia and bipolar I disorder. While olanzapine is one of the most effective second-generation antipsychotics, its use has long been limited by substantial weight gain and metabolic side effects. The addition of samidorphan, an opioid receptor antagonist, represents an innovative approach to mitigate these concerns. We’ll dive into the pathophysiology of schizophrenia and bipolar I disorder, review current treatment strategies, and then unpack the evidence behind OLZ/SAM—including its mechanism of action, clinical trial results, metabolic profile, and potential role in trea...

Combining aripiprazole and haloperidol presents a clinical and pharmacological puzzle. On one hand, you have haloperidol, a potent D₂ antagonist that fully blocks dopamine; on the other, aripiprazole, a partial agonist with high affinity that displaces the antagonist only to provide a weaker signal. This interplay can be dangerous, potentially triggering a "dopamine supersensitivity psychosis" in a brain already adapted to chronic blockade, leading to a sudden worsening of symptoms. Yet, this same mechanism can be harnessed to treat stubborn side effects like hyperprolactinemia, making it a tempting strategy. In this episode of PsyQ, we dissect the competing pharmacology, re...

In this episode of PsyQ, we journey from the historical notion of "gut feelings" to the cutting edge of psychiatric research: the microbiota-gut-brain axis. This episode unravels the paradigm shift that recast the gut's microbial inhabitants as a dynamic metabolic organ, actively shaping our mental health. We dissect the core communication network, exploring how neural (vagus nerve), endocrine (HPA stress axis), and immune (cytokine) pathways form a three-way dialogue between our microbes and our mind. Delving into the 'chemical language' of the gut, we discuss how microbial metabolites like short-chain fatty acids and bile acids modulate brain function by...

This episode of PsyQ delves into the rare and puzzling condition of non-catatonic mutism in individuals with schizophrenia, a profound silence that is not attributable to the physical inability to speak or the classic signs of catatonia. We explore the case of "Mr. X," a man who was mute for three years, to understand the complexities of diagnosis and the surprising cultural patterns that see this condition reported more frequently in specific regions like the Indian subcontinent. The discussion covers the crucial distinctions from catatonic mutism, potential neurological underpinnings, and the profound psychological impact on patients. Furthermore, we reveal...

The field of psychiatry is at a technological crossroads, with Artificial Intelligence promising to revolutionize care delivery amidst a global mental health crisis. But does this new frontier offer a solution or a source of new, profound harm? This episode of PsyQ: Journal Club takes a critical, evidence-based look at the role of Large Language Models (LLMs) in mental health, moving beyond the hype to provide clinicians with a guide to responsible innovation. We explore a comprehensive framework for safely augmenting clinical practice, examine a case study in using digital phenotyping to forecast mental states in schizophrenia, and confront...

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...

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...

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:<...

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...

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...

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...

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 an...

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...

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.<...

Timestamps

(0:00) Context & Rationale

(11:25) Methods & Findings

(27:06) Critical Appraisal

(43:26) Impact & Clinical Takeaway

This is a journal club discussion on the CATIE trial. We cover the study's background and methodology to its critical appraisal and clinical impact. Keep in mind this merely a summary of a journal article and with the use of AI we are susceptible to some hallucination. Please refer to the source material linked below for the most accurate information about the CATIE Trial.

https://www.nejm.org/doi/full/10.1056/NEJMoa051688