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. 2025 Feb 27;3(1):53-58.
doi: 10.1089/psymed.2024.0032. eCollection 2025 Mar.

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

Shakila Meshkat  1   2 , Erica Kaczmarek  1   2   3 , Zoe Doyle  1   2 , Ryan M Brudner  1   2 , Fabiano A Gomes  4 , Marc G Blainey  1 , Geneva Weiglein  1 , Roger S McIntyre  1   2   3   5   6 , Rodrigo B Mansur  1   5 , Joshua D Rosenblat  1   2   3   5
Affiliations

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

Shakila Meshkat et al. Psychedelic Med (New Rochelle). .

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.

Keywords: bipolar II disorder; efficacy; psilocybin; psychedelics; treatment-resistant depression.

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