40319349; PMCID: PMC12143125. HOW DURABLE ARE ACUTE EFFECTS OF PSILOCYBIN ON TREATMENT-RESISTANT DEPRESSION?

Treatment resistant depression (TRD) affects a significant number of patients who experience major depression episodes. When patients experience TRD, even if responsive to treatment, the likelihood of relapse is greater. The use of psilocybin, often referred to as a classic psychedelic because of its action on serotonin receptors, has been studied for the treatment of depression and TRD in a number of pilot studies and more recently in Phase 2 studies with Phase 3 studies ongoing. While early results are promising, few studies have reported observations beyond the acute response to usually single-dose psilocybin treatment. Clinical trials of psilocybin for acute depression in smaller trials both controlled and open report striking acute response rates of 50% or greater response rates at primary outcome. The larger Phase 2 studies are less optimistic but still reporting significant positive impact for acute effects. 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). Early findings support that those who response initially to psilocybin with diminished depression symptoms often show improvement in other domains such as anxiety and quality of life, however the persistence of response and remission does not necessarily extend over many months. During the workshop we will review studies on the long-term durability of depression response to psilocybin. We will focus on outcomes in mood as well as other domains such as quality of life.

References

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