rich 1.0 Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Henry Nasrallah, MD, to discuss off-label prescribing and polypharmacy. Nasrallah bases the discussion off his landmark analysis that demonstrated 88% of DSM psychiatric diagnoses have no US Food and Drug Administration (FDA)-approved pharmacotherapy, leaving clinicians with no choice but to prescribe off-label for many of the patients they encounter. He argues that the FDA's diagnosis-centric approval framework, rather than a symptom- or circuit-based model, is a primary driver of this gap, noting that a shift toward symptom-level indications could render irrelevant much of current off-label practice. Both clinicians emphasize that off-label prescribing, when rationale-based and neuroscientifically informed, constitutes responsible clinical care rather than reckless deviation. Nasrallah describes examples like using valproate for impulsive aggression in traumatic brain injury, clozapine augmentation for treatment-resistant suicidality, and high-dose modafinil for refractory depression—each grounded in mechanistic reasoning. Goldberg observes that "off-label practices are legitimate…good for patients and save a lot of lives," while cautioning that prescribers must understand what a drug does in the brain, not merely follow or ignore labeling. The conversation also addresses the transdiagnostic model, polypharmacy, insurance barriers to off-label coverage, and the underutilization of clozapine. Nasrallah concludes by characterizing off-label discovery as "a creative process, the cutting edge of scientific advances," urging clinicians to publish case reports and share serendipitous findings to catalyze future trials. Brain Trust: Conversations in Psychopharmacology https://audioboom.com/channels/5169832-brain-trust-conversations-in-psychopharmacology Audioboom https://audioboom.com 480 95 https://audioboom.com/i/43675319/600x600/c 600 600 <iframe width="100%" height="95" src="https://embeds.audioboom.com/posts/8911034/embed?v=202301" style="background-color: transparent; display: block; padding: 0; width: 100%" frameborder="0" allowtransparency="allowtransparency" scrolling="no" title="Audioboom player" allow="autoplay" sandbox="allow-downloads allow-forms allow-popups allow-same-origin allow-scripts allow-storage-access-by-user-activation allow-top-navigation-by-user-activation"></iframe>