PsyQ: Journal Club

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 accelerated clearance for MDD in 2025; SAINT cleared for TRD), coverage gaps (daily caps vs 5x/day), and how to counsel patients on choosing between speed, access, and cost. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 provide a critical guide for clinicians to navigate a healthcare landscape where the pursuit of profit often conflicts with the mission of healing. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 threats emerge, and embrace psychiatry’s dual role as healer and advocate for safer communities. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 where ketamine helped patients who were medically unfit for ECT (e.g., cardiomyopathy, advanced lung disease) and improved within hours to days—illustrating ketamine’s potential role as a bridge or alternative in treatment-resistant catatonia, especially in mood-disorder presentations. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 ensuring care, distinguishing culturally appropriate concordance from prejudice, and leading post-incident team recovery—so trainees can respond clearly, ethically, and confidently. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 treatment-resistant cases. Along the way, we’ll highlight clinical pearls, prescribing considerations, and real-world implications for psychiatry trainees navigating the complexities of antipsychotic treatment. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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, review the conflicting case literature—from successful augmentation to severe relapse—and provide evidence-based, practical guidance on how to navigate this combination. Join us for a deep dive into this double-edged sword of psychopharmacology, equipping you with the knowledge to proceed with caution and confidence. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 influencing key cells like microglia and the integrity of the blood-brain barrier. Finally, we critically examine the clinical implications for disorders like autism and depression, evaluating the current evidence, promises, and pitfalls of therapeutic strategies such as psychobiotics and fecal microbiota transplantation, and look toward the future of this revolutionary field.References:Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13(10), 701–712.Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024). Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduction and Targeted Therapy, 9(1), 37.Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021). The gut microbiota–brain axis in behaviour and brain disorders. Nature Reviews Microbiology, 19(4), 241–255. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 a surprising "game-changer" in treatment, highlighting how ECT, particularly when combined with other medications in a "triple therapy" approach, has shown remarkable success in restoring speech, offering significant hope where conventional treatments have often failed. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 the chilling evidence of how current "therapy bots" fail in moments of crisis by expressing stigma, colluding with delusions, and dangerously mishandling suicidal ideation. We argue that the future is not the autonomous AI therapist, but a human clinician empowered by validated tools, and we provide a playbook for how psychiatrists can become the essential "ethical guardians" and "digital augurs" in this new era. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 StudyMultimodal Interventions Are More Effective in Improving Core Symptoms in Children With ADHDA 14-Month Randomized Clinical Trial of Treatment Strategies for Attention-Deficit/Hyperactivity DisorderYoung adult outcomes in the follow-up of the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder: symptom persistence, source discrepancy and height Suppression This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com

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 Psychiatry2. Hippius (1999). A Historical Perspective of Clozapine. J Clin Psychiatry3. 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 is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit upathak.substack.com