Balancing Efficacy and Metabolic Risk: Olanzapine/Samidorphan (OLZ/SAM) in Clinical Practice - PsyQ Episode 16

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