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Global lifetime prevalence of 15-20%. WHO ranks depression as the leading cause of disability worldwide. 280 million people affected globally. In Switzerland, 12-month prevalence is approximately 7%.
SSRIs/SNRIs as first-line, psychotherapy (CBT, IPT), combination therapy. 30-40% of patients do not respond adequately to first-line treatment. Full remission is achieved in only 30-40% of cases with initial treatment.
Psilocybin shows the strongest evidence in MDD. Just 2 sessions produced rapid, sustained antidepressant effects. Ketamine/esketamine for acute stabilization. Ayahuasca showed rapid effects in a single-session RCT. All three substances target different neurobiological pathways than traditional antidepressants.
Psilocybin: effect size d=2.5 vs. waitlist (Davis et al., 2021). Comparable to or exceeding esketamine in head-to-head comparison (Goodwin et al., 2022 NEJM). Ayahuasca: significant improvement at 7 days in RCT (Palhano-Fontes et al., 2019).