{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:26:15Z","timestamp":1788272775685,"version":"build-2803163510"},"reference-count":52,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Psychother Psychosom"],"abstract":"<jats:p>Introduction: Psilocybin shows promise for treatment-resistant depression (TRD), but long-term data are limited. This study examined the antidepressant effect of one or two doses of psilocybin with adjunct psychotherapy in TRD until 12 months. Methods: This is a naturalistic follow-up of a phase 2b, randomized, active placebo-controlled trial in adults with TRD, where participants were randomized to receive two drug administrations 6 weeks apart, embedded within seven psychotherapeutic sessions: (1) active placebo (100 mg nicotinamide), then 25 mg psilocybin, (2) 5 mg psilocybin, then 25 mg psilocybin, (3a) 25 mg psilocybin, then 5 mg psilocybin, or (3b) 25 mg psilocybin twice. The controlled phase ended at 12 weeks, after which participants could pursue other treatments, with follow-ups at 6 and 12 months. The primary follow-up endpoint was change from baseline on the Hamilton Rating Scale for Depression (HAMD17). Results: Overall, 126\/144 randomized participants (51 females, 40%) completed at least one follow-up visit. Mean baseline HAMD17 scores across groups ranged from 21.6 to 22.2. A generalized additive mixed regression model for change in HAMD17 scores showed a significant time effect across groups for both follow-up time points, with estimated average changes from baseline of \u22127.93 (95% CI: \u22129.17 to \u22126.70, adj. p &lt; 0.0001) at 6 months and \u22127.74 (95% CI: \u22129.04 to \u22126.43, adj. p &lt; 0.0001) at 12 months, without significant group differences. Results were consistent when controlling for antidepressant pharmacotherapy and psychedelic use. Re-initiation of antidepressant pharmacotherapy during follow-up was strongly associated with higher HAMD17 scores (\u03b2 = 3.79, 95% CI: 1.98 to 5.60). Conclusion: This is the largest and most complete systematic follow-up of any clinical psychedelic trial. The findings demonstrate a stable and clinically meaningful long-lasting antidepressant effect of one or two 25 mg doses psilocybin with adjunct psychotherapy up to 12 months in TRD.<\/jats:p>","DOI":"10.1159\/000552272","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T16:00:52Z","timestamp":1779897652000},"page":"1-18","source":"Crossref","is-referenced-by-count":1,"title":["Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression: 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial"],"prefix":"10.1159","author":[{"given":"Lea 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