Worsening suicidal ideation and prolonged adverse event following psilocybin administration in a clinical setting: case report and thematic analysis of one participant's experience

A participant in a phase 2b clinical trial of psilocybin for treatment-resistant depression experienced increased suicidal ideation and a prolonged period of severely restricted eating after administration, leading to destabilization and need for support. Despite limited improvement on depression rating scales, the participant found the experience helpful and made beneficial life changes. The case suggests psilocybin can temporarily worsen suicidal ideation and cause prolonged adverse events beyond acute effects, while paradoxically improving functional outcomes not captured by standard scales. Qualitative exploration of serious adverse events and participant accounts is needed to better understand psilocybin's varied outcomes.

Study at a glance

Abstract

Background Psilocybin is being investigated as a treatment for a myriad of disorders, including treatment-resistant depression. The main focus has been on positive effects, with little attention paid to negative outcomes, especially in clinical settings. Quantitative methodology limits further exploration of such events and can also miss improvements not captured on rating scales. Aims To highlight potential adverse events of psilocybin and underline limits of quantitative methodology, calling for process evaluations alongside clinical trials. Case presentation This is a case of a participant in a phase 2b clinical trial of psilocybin for treatment-resistant depression who presented with increased suicidal ideation and a prolonged period of severely restricted eating following administration, leading to a period of destabilisation and a need for support. Despite the difficulties encountered and the participant's limited improvement on rating scales, she found the experience to have been helpful and led her to make changes to her life which she found beneficial. She described her experience in a written account to the authors. Method The case was summarised and the written account was thematically analysed and synthesised into a logic model. Conclusions Psilocybin could lead to temporary worsening of suicidal ideation and instigate prolonged adverse events that outlast its acute effects. Paradoxically, it could simultaneously lead to an improvement in functional outcomes which is not clear on depression rating scales. This calls for a qualitative exploration of serious adverse events and participant accounts to deepen our understanding of the psilocybin experience and its different outcomes.