AMCP Market Insights: Optimizing managed care approaches to treatment-resistant depression

Treatment-resistant depression (TRD) is a subset of major depressive disorder (MDD) most commonly defined as failure to respond to 2 or more antidepressant regimens despite adequate dose, duration, and adherence to treatment. The burden of TRD impacts individuals, families, and society, with outcomes such as decreased health-related quality of life and increased health care utilization and costs. To address the unmet need in many mental health conditions, psychedelic-assisted treatment such as psilocybin for TRD is emerging as a potential option. To discuss optimizing managed care approaches to TRD including the use of psilocybin, AMCP Market Insights virtually convened an expert panel of managed care stakeholders in March 2026. This article provides a qualitative summary of the panel discussion along with key insights and suggested payer practices meant to support informed coverage decisions and guide future work such as collaboration, research, and advocacy. Key insights underscore that there is a high unmet need in TRD and that mitigating barriers to care is a priority for payers. Perspectives on the current evidence for psilocybin in TRD are mixed; payers want additional data to compare treatments, elucidate the appropriate treatment population, and assess cost-effectiveness. Additionally, a primary challenge with psilocybin treatment will be an adequate network of mental health professionals to oversee administration and observation and to provide post-treatment care. Examples of suggested payer practices include education, collaboration, prioritizing behavioral health network readiness and quality, and mitigating barriers to care.