Which Psychotherapy Model Should be Used in Psilocybin Treatment for Depression?

OBJECTIVE: Unipolar and bipolar depression severely impact millions of individuals worldwide, with a significant subset of cases remaining unresponsive to conventional treatments. Psilocybin-assisted psychotherapy (PAP) has demonstrated therapeutic efficacy; however, the optimal psychotherapeutic approach remains undefined, ranging from unstructured models rooted in historical practices to modern frameworks that are structurally tailored for depression. This narrative review proposes a conceptualization of psychotherapeutic models employed in existing interventional trials of PAP for depression and provides a preliminary comparison of their main characteristics and evidence for efficacy. METHODS: The online databases PubMed, PsycINFO, and Google Scholar were searched for interventional trials evaluating PAP for individuals with unipolar or bipolar depression. RESULTS: A total of 38 publications were reviewed, contributing to the conceptualization of two main types of psychotherapy models: 1) 'Specific' approaches (most commonly Acceptance and Commitment Therapy and Perceptual-Control Therapy) and 2) 'Non-specific' models of psychological support. Both models emphasize the critical role of the therapeutic alliance, yet differ in mechanistic focus, with specific models being developed to enhance psychological flexibility and non-specific models emphasizing the concept of the 'inner-healer.' Importantly, critical gaps in the literature were identified, including methodological limitations of current evidence and the need for standardized reporting guidelines. CONCLUSION: Although each PAP model differs, both may have clinical relevance in depression treatment. Future work should explore the standardized reporting of psychological interventions in PAP and comparative study designs to better evaluate non-specific and specific models and inform treatment guidelines.