In a systematic review and meta-analysis of 12 controlled clinical trials involving 733 adults with depressive symptoms, psychedelic-assisted therapy (PAT) with psilocybin or LSD produced a large overall reduction in depressive symptoms compared to control conditions. More hours of preparation therapy before the psychedelic session were significantly linked to greater symptom reduction. However, the number of post-dosing integration therapy hours, total therapy sessions, and longer follow-up periods were not associated with better outcomes. Most studies had high risk of bias due to ineffective blinding. The findings suggest that preparation therapy may be a key component in optimizing PAT outcomes, but further research is needed.
For patients with difficult-to-treat depression who do not respond to at least two antidepressant trials, remission rates are significantly lower than the 67% seen with initial or secondary pharmacological treatment. Brain stimulation procedures and novel substances offer innovative and effective options to complement standard therapies. This overview covers repetitive transcranial magnetic stimulation, electroconvulsive therapy, ketamine/esketamine, transcranial direct current stimulation, deep brain stimulation, and psychedelic-assisted psychotherapy, with an outlook on individualized, procedure-specific indications.