LONG TERM OUTCOMES FROM PSILOCYBIN AND RESPONSE TO RE-DOSING FOR DIFFICULT TO TREAT DEPRESSION

The questions of how durable are responses to psilocybin, a classic psychedelic, and are there ways to optimize responses in difficult to treat depression (TRD). While the relative percent of patients treated for depression that will have limited response is known and substantial (up to 30%), it is also know when patients experience TRD the likelihood of relapse is greater even after a response to treatment. While early acute results in Phase 2 and both open and controlled pilot studies is promising, there have been few observations beyond acute effects for the impact longer term of psilocybin treatment for TRD. Clinical trials of psilocybin for acute depression in smaller trials both controlled and open report striking acute response rates of 50% or greater at primary outcome. The larger Phase 2 studies are less optimistic but still reporting significant positive impact for acute effects. Phase 3 studies are currently ongoing for TRD. By contrast few studies to date have followed up patients longer term with only two reporting six-month outcomes (Carhart-Harris et al., 2018; Erritzoe et al., 2024) and two reporting 12-month outcomes (Ellis et al., 2025; Goodwin et al., 2025). Results from longer term follow up studies will be presented and discussed. Of particular interest there have been almost no reports of redosing following a period after the first doses. We will focus on a recent case series completed more than one year after acute dosing. Of note, this case series demonstrated greater variability of response compared to the first dosing with some participants making greater improvements, some recapturing a previous response but lacking durability, and some with limited response. During the workshop we will review studies on the long-term durability of depression response to psilocybin, and the results from a recent case series examining redosing after more than a year from first dosing.

References

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