Advancing Real-World Effectiveness Evidence for Rapid-Acting Psychotropic Interventional Drugs

Presenters

Adam Haim, Ph.D.
Division of Services and Interventions Research

Jonathan Sabbagh, Ph.D.
Division of Translational Research

Goal

The overarching goal of this concept is to encourage research that aims to better understand the real-world effectiveness of rapid-acting psychotropic interventional drugs (RAPIDs) in heterogenous patient populations and generate the actionable evidence needed by healthcare systems to guide broad clinical implementation.

Rationale

RAPIDs, including ketamine/esketamine, serotonergic compounds such as psilocybin and 3,4-methylenedioxymethamphetamine (MDMA), and other emerging compounds, are being studied and, in some cases, used in clinical settings for serious mental illnesses and related mental health conditions, including treatment-resistant or treatment-refractory conditions, suicidal ideation, and behaviors for which existing FDA-approved treatments may not produce adequate or durable clinical benefit. RAPIDs can produce clinically meaningful symptom reduction on a timescale of hours to days in individuals with mental illnesses and are distinguished from other daily take at home pharmacotherapies by the need for structured clinical delivery, in-clinic monitoring, or specialized follow-up. The near-term implementation and research challenge is no longer limited to whether RAPIDs can work under tightly controlled conditions; the urgent question is how they should be delivered safely, effectively and sustainably in real-world care to optimize the full benefit for individuals living with mental illnesses.

Highly controlled, efficacy-focused clinical trials remain essential for establishing safety and acute symptom relief for regulatory approval. However, many practical questions require complementary approaches, including pragmatic clinical trials, hybrid effectiveness-implementation studies, and analyses of real-world clinical outcome data. A coordinated, systematic approach is necessary to address broad questions about generalizability, care settings, safety monitoring, retreatment, adjunctive support, and long-term clinical outcomes. In particular, strategies are needed to advance the coordinated collection of rigorous evidence that can guide care standards for clinical practice, implementation, and sustainable health system adoption for RAPIDs.