In this episode of PsyQ, we confront the "zone of danger" in acute suicidality—the critical lag period where standard antidepressants often fail to address immediate "psychache". Anchored by the seminal Yovell et al. (2016) randomized controlled trial, we explore the neurobiological overlap between physical and social pain , testing the hypothesis that ultra-low-dose buprenorphine (starting at 0.1 mg) can modulate the endogenous opioid system to treat separation distress directly. We dissect the study's groundbreaking findings—including a significant reduction in suicidal ideation distinct from depression improvement and robust efficacy in patients with Borderline Personality Disorder —while rigorously outlining the safety parameters, zero-withdrawal protocols, and the critical clinical distinction between treating specific depressive symptoms and soothing the primal agony of the PANIC/GRIEF system.

In this episode of PsyQ, we review a large national inpatient study examining the association between cannabis use disorder (CUD) and suicide attempts/self-harm among hospitalized adolescents in the United States. Using data from more than 800,000 adolescent hospitalizations, the study demonstrates that CUD is independently associated with approximately 40% increased odds of suicide attempts and self-harm, even after controlling for psychiatric and substance use comorbidities. The data further highlight depression as a key moderator, with adolescents experiencing both CUD and depression showing markedly higher suicide risk compared to those with either condition alone. The findings reinforce the importance of routine substance use screening, suicide risk assessment across all inpatient settings (not just psychiatric units), and implementation of dual-diagnosis treatment approaches targeting both cannabis use and co-occurring psychiatric illness. These results are particularly relevant given rising cannabis use among adolescents and shifting risk perceptions related to legalization and accessibility.

In this episode of PsyQ, we review the landmark STEP-BD randomized controlled trial evaluating the effectiveness of adjunctive antidepressant treatment for bipolar depression. We analyze the study's methodology, specifically the use of equipoise-stratified randomization to mirror routine clinical care and the selection of "durable recovery"—defined as eight consecutive weeks of euthymia—as the primary outcome measure. The discussion focuses on the key data points demonstrating that the addition of standard antidepressants (bupropion or paroxetine) to mood stabilizers provided no statistically significant benefit over placebo in achieving durable recovery. Furthermore, we examine the safety findings, which indicated that adjunctive antidepressant use was not associated with an increased risk of treatment-emergent affective switch compared to mood stabilizers alone.

References

Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression. N Engl J Med. 2007;356(17):1711-1722.

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 medications and pivot to interventional psychiatry.

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 elevated suicide risk. Although stimulant treatment remains effective for short-term symptom control, long-term functional normalization is inconsistent, underscoring that medication alone is insufficient. This episode reframes childhood ADHD as a chronic, life-course disorder with major implications for early intervention, comorbidity management, and long-term care planning.

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 extinction. Join us as we explore how decoupling alcohol from its neurobiological reward can bridge the massive treatment gap for binge drinkers who are resistant to total abstinence.

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 those that are not, and explore the paper's most critical clinical implication: its finding that early mood worsening is not associated with discontinuation, providing a data-driven framework for distinguishing withdrawal from true depressive relapse