Evidence map›Paper›PMID 42201843›Full record

ArticlePsychotherapy and psychosomatics2026

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.

Lea J Mertens, Felix Betzler, Manuela Brand, Ricarda Evens, Andrea Jungaberle, Henrik Jungaberle, Laura Kärtner, Tomislav Majić, Christian N Schmitz, Andreas Ströhle and 17 more

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Article in Psychotherapy and psychosomatics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Lea J MertensDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, lea.mertens@zi-mannheim.de.
Felix BetzlerCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Manuela BrandDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Ricarda EvensCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Andrea JungaberleCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Henrik JungaberleMIND Foundation, Berlin, Germany.
Laura KärtnerDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Tomislav MajićCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Christian N SchmitzDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Andreas StröhleCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Dennis ScharfDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Moritz SpangemacherDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Max WolffDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Zahra AssadiCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Scharif BahriCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Lilith BecherCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Luca V FärberDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Henry HarderDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Niklas KirchenDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Eugenia KulakovaCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Linda C KunzDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Andy MeijerCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Barbara RohrmoserDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Stefan WellekGerman Center for Mental Health (DZPG), partner site Mannheim - Heidelberg - Ulm, Mannheim, Germany.
Moritz M BergerCore Facility of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Michael KoslowskiCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany.
Gerhard GründerDepartment of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, gerhard.gruender@zi-mannheim.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionPsilocybin 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.

methodsThis 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).

resultsOverall, 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 -7.93 (95% CI: -9.17 to -6.70, adj. p < 0.0001) at 6 months and -7.74 (95% CI: -9.04 to -6.43, adj. p < 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 (β = 3.79, 95% CI: 1.98 to 5.60).

conclusionThis 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.

Indexed as

Clinical trialLong-term follow-upPsilocybinTreatment-resistant depression

Identifiers

PMID42201843
PMCPMC13412222

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.