Psilocybin with psychological support for treatment-resistant depression: six-month follow-up.
R. L. Carhart-Harris, Mark Bolstridge, C. M. J. Day, J. Rucker, R. Watts, David Erritzøe, Mendel Kaelen, Bruna Giribaldi, Michael Bloomfield, Steve Pilling, James A Rickard, Ben Forbes, Amanda Feilding, D. Taylor, Hv Curran, D. J. Nutt
Psychopharmacology (Berl) November 8, 2017 DOI: 10.1007/s00213-017-4771-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label trial Randomized Double-blind Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Patients with severe, unipolar, treatment-resistant major depression |
| Intervention | Psilocybin |
| Dose | 10 and 25 mg |
| Duration | 7-day interval between doses; assessments from 1 week to 6 months post-treatment |
| Topics | Depression Psychedelic-assisted therapy Psilocybin |
| Keywords | Psilocybin therapy Psilocybin-assisted treatment Mushroom therapy Hallucinogen treatment Refractory depression Severe depression Chronic depression Persistent mood disorder Intractable depression Mental health treatment Psychiatric intervention Mood disorder therapy Psychological support Mental wellness Novel therapies Alternative treatments Experimental interventions Innovative medicine Breakthrough treatments |
| Citations | 978 |
| Key findings | Two doses of psilocybin produced large, rapid reductions in depressive symptoms that persisted for six months in patients with treatment-resistant depression. |
Abstract
Rationale: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy.
Objectives: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression.
Methods: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure.
Results: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience.
Conclusions: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.
In the evidence
This study is part of the evidence base for 4 syntheses in the library. Here is how each one recorded it.
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Two psilocybin doses produced large reductions in depressive symptoms (Cohen's d = 2.2 at week 1, 1.4 at 6 months) that remained significant at six months.
Synthesized
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Two doses of psilocybin produced large, rapid reductions in depressive symptoms that persisted for six months, with large effect sizes at 5 weeks and 3 and 6 months.
Synthesized
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State of the evidence: Depression Supports
Two doses of psilocybin produced large, rapid reductions in depressive symptoms that persisted for six months in patients with treatment-resistant depression.
Synthesized
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State of the evidence: Psilocybin Supports
Two doses of psilocybin produced large, rapid reductions in depressive symptoms that remained significant at 3 and 6 months, with effects predicted by the quality of the acute psychedelic experience.
Synthesized
Comparable studies
Other non-randomized and open-label trials on psilocybin and psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Patients with major depressive disorder | 2021 | Open-label study | n = 24 |
| HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. Cancer patients with a DSM-5 depressive disorder (major depressive disorder or... | 2023 | Open-label feasibility and safety pilot study | n = 12 |
| Group psychedelic therapy: empirical estimates of cost-savings and improved access Adults with PTSD or major depressive disorder eligible for psychedelic-assisted therapy... | 2023 | Comparative cost analysis using trial data and published estimates | |
| Increased low-frequency brain responses to music after psilocybin therapy for depression. Patients with treatment-resistant depression | 2023 | Open-label trial | n = 19 |
| Group format psychedelic-assisted therapy interventions: Observations and impressions from the HOPE trial Patients with a DSM-5 depressive disorder associated with a cancer diagnosis | 2023 | Open-label feasibility and safety pilot study |