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Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression in Bipolar II Disorder

Shakila Meshkat, Erica Kaczmarek, Zoe Doyle, Ryan M Brudner, Fabiano A Gomes, Marc G Blainey, Geneva Weiglein, Roger S McIntyre, Rodrigo B Mansur, Joshua D Rosenblat

Psychedelic Medicine November 18, 2024 DOI: 10.1089/psymed.2024.0032 via OpenAlex

Summary

AI-generated from the abstract

In a small subgroup analysis of four adults with treatment-resistant depression associated with bipolar II disorder, two 25 mg doses of psilocybin combined with psychotherapy were associated with reductions in depressive symptoms. The average depression score on the Montgomery–Åsberg Depression Rating Scale dropped from 32.5 at baseline to 20.3 two weeks after the first dose, and to 19 two weeks after the second dose; at six months the average score was 21.3. Mania ratings remained stable, and no mania, hypomania, or psychosis occurred. The authors suggest psilocybin may improve depressive symptoms in bipolar II disorder but call for larger studies to confirm the findings.

Study at a glance

Characteristics Subgroup analysis of an open-label trial Peer reviewed
Sample size 4
Population Adults with treatment-resistant depression associated with bipolar II disorder, excluding those with psychosis
Intervention Psilocybin
Dose 25 mg
Duration 6-month study
Topics Depression Psilocybin
Keywords Bipolar ii disorder Efficacy Psychedelics Psilocybin therapy
Citations 8
Key finding Psilocybin administration was associated with reduced depressive symptoms and no treatment-emergent mania, hypomania, or psychosis in four participants with bipolar II disorder.

Abstract

Background: Bipolar II disorder (BD-II) is often associated with chronic and treatment resistant major depressive episodes. Psilocybin has shown promise for its rapid-acting antidepressant effects, though its impact on bipolar depression remains unexplored. In the present subgroup analysis of an already published trial on treatment-resistant depression (TRD), we aimed to preliminarily evaluate the safety and efficacy of psilocybin in patients with BD-II. Methods: Adults with TRD associated with BD-II, excluding those with psychosis were included. Participants underwent one or two psilocybin sessions, each with a dose of 25 mg, along with preparatory and integrative psychotherapy sessions. Results: A total of four participants with a mean age of 37.5 ± 4.15 years were included. At baseline, the mean Montgomery–Åsberg Depression Rating Scale (MADRS) score was 32.5 (95% CI: 26.3–38.7, SD = 3.87). By week 2 post-dose, mean MADRS decreased to 20.3, and 2 weeks after dose 2, it further dropped to 19. At the end of the 6-month study, the mean MADRS score was 21.3. Young Mania Rating Scale scores remained stable at a mean of one throughout the study with no evidence of treatment emergent mania, hypomania or psychosis observed in any participants. Conclusions: These findings suggest potential improvement in depressive symptoms with psilocybin administration in BD-II. Future studies with larger sample size are required to replicate our results and further evaluate antidepressant effects of psilocybin in bipolar depression.

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