Predictors of therapeutic response to psychedelic-assisted therapy: A systematic review

Psychedelic-assisted therapy (PAT) has demonstrated substantial efficacy across a range of mental disorders. However, heterogeneity between patients confers differential responsiveness. This systematic review aims to explore factors which may predict therapeutic responses to PAT.

A systematic search was performed from inception through to March 2024 and studies that assessed predictors of response related to the use of classic psychedelics for mental disorders were included.

A total of 54 studies investigating potential predictors of treatment response to psychedelic-assisted therapy were included in the review. These studies encompassed adult populations diagnosed with substance-use disorders, major depressive disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder and existential distress related to life-threatening illness as well as naturalistic samples reporting psychopathological symptoms without a formally confirmed diagnosis. The most frequently reported predictor of therapeutic response was the intensity of the acute psychedelic experience, particularly mystical-type experiences (MTEs), though this was not consistent across all disorders or time points. Factors related to set, setting and dose were frequently associated with the likelihood and intensity of MTEs.

The acute psychedelic experience, especially MTEs, was the most frequently reported predictor of therapeutic response. Future trials should explore a broader range of predictors, include longer-term follow-up and improve methodological consistency to strengthen the evidence base for reliable predictors of therapeutic response.