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CONDUCTING CLINICAL TRIALS USING COMBINED TREATMENT MODALITIES: CHALLENGES, OPPORTUNITIES, AND INSIGHTS FOR FUTURE REGULATORY CONSIDERATION

Samuel Wilkinson — Yale School of Medicine

2026 ASCP Annual Meeting

Advances in interventional psychiatry have created new opportunities to combine therapeutic modalities in clinical trials to improve outcomes for patients with treatment-resistant psychiatric disorders. This panel presents the work of three labs (Pittsburgh, Yale, Calgary) that have developed lines of research of trial evaluating the feasibility and efficacy of combined treatment modalities. Here, we outline methodological principles and insights from these efforts. The principles employed by the approach of these three labs include: (1) interventional techniques capable of rapidly altering dysfunctional neural circuits; (2) psychological or behavioral interventions that capitalize on periods of enhanced neuroplasticity; or (3) pharmacologic or biologic treatments with rapid onset or synergistic mechanisms. Early trials suggest that coordinating treatments within windows of enhanced plasticity may amplify therapeutic effects, though definitive efficacy data require larger controlled trials. The panel will discuss challenges and opportunities of these trial designs, as well as recent feasibility and efficacy data. The discussant (Yaseen from FDA) will converse ways that regulatory authorities consider combined modality treatment trials. The insights from this panel are highly applicable to ongoing discussions about how best to move forward in multimodality treatment design, including in the nascent psychedelic space, which often combines powerful biological therapies with a psychotherapeutic approach.

Learning Objective 1: To understand the challenges and opportunities of designing and conducting trials of combined treatment modalities

Learning Objective 2: To understand the challenges and limitations of the regulatory aspects of these trial designs

References

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