Evaluating the Risk of Psilocybin for the Treatment of Bipolar Depression: A Systematic Review of Published Case Studies

This systematic review of published case studies evaluates the potential risks of treating bipolar depression with psilocybin.

ABSTRACT

Objective: Given the treatment limitations of depression in bipolar disorder, we evaluated the known risks of using psilocybin (and similar substances). This includes a systematic assessment of published case histories, to assess the risk of psilocybin as a treatment of depression in bipolar disorder.
Data Sources: A comprehensive search of case studies published through December 31, 2020 was conducted using the following electronic databases: PubMed, Web of Science, and PsychInfo, focusing on classic psychedelics and case studies or case histories.
Study Selection: Our search terms resulted in 541 hits, of which 43 were non-duplicates of case studies with individuals having an adverse reaction to a psychedelic substance. Of those, 15 case studies indicated some form of adverse event involving mania or manic like behavior that persisted beyond the acute intoxication of the substance.
Data Extraction: Two independent evaluators assessed all possible cases, focusing on manic behavior based on DSM criteria. Two separate evaluators convened to evaluate cases where the case information was unclear.
Results: Of the 15 cases, four involved psilocybin, two cases involved individuals with a likely pre-existing diagnosis of bipolar disorder, and three involved individuals without a history of polysubstance abuse or concurrent polysubstance use.
Conclusions: We conclude that there is some evidence of risk of activating mania with these substances, but that the risk does not appear to be strong or overwhelming. Instead a careful prospective study, such as an open-label treatment protocol with careful controls, appears warranted in this population.

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