The impact of antidepressant discontinuation prior to treatment with psilocybin for treatment-resistant depression.
Lindsey Marwood, Megan Croal, Sunil Mistry, Hollie Simmons, Joyce Tsai, Matthew B Young, Guy M. Goodwin
Journal of Psychiatric Research December 1, 2024 DOI: 10.1016/j.jpsychires.2024.10.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc analysis of a phase II randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 233 |
| Population | Participants with treatment-resistant depression |
| Intervention | COMP360 psilocybin |
| Dose | 25 mg, 10 mg, or 1 mg |
| Duration | 3-week primary endpoint |
| Topics | Depression Psilocybin |
| Keywords | Psychedelic medicine Mental health trials Psychedelic treatment Antidepressant discontinuation Psychedelics Randomized clinical trial Medication tapering |
| Citations | 9 |
| Key findings | Antidepressant drug discontinuation did not compromise psilocybin treatment efficacy or the subjective psychedelic experience in participants with treatment-resistant depression. |
Abstract
It has been suggested that the recent use and discontinuation of antidepressant drugs compromises the action of psilocybin. As evidence is only available from small or uncontrolled samples, this post hoc analysis investigated this using data from the largest, phase II, randomized controlled trial of psilocybin treatment to date. Data from 233 participants with treatment-resistant depression (TRD) who received 25 mg, 10 mg, or 1 mg of investigational drug COMP360 psilocybin (a proprietary, pharmaceutical-grade synthetic psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.), administered with psychological support, were compared for groups of participants who either discontinued one or more antidepressant drugs during screening or entered the trial antidepressant drug free. Measures of depression symptom severity change during the antidepressant drug discontinuation period, baseline suicidality, acute subjective psychedelic effects, and the study's primary endpoint (change in depression symptom severity between Baseline and Week 3) are described for both groups. Antidepressant drug discontinuation was not related to worsening of depression severity before Baseline. Suicidality was comparable between groups at Baseline. Psilocybin treatment efficacy and the subjective psychedelic experience did not appear to be compromised by antidepressant drug discontinuation. Thus, it does not limit the feasibility of psilocybin treatment for the future. These findings also support the overall homogeneity of our findings with psilocybin treatment as a monotherapy for TRD. The prior contradictory reports may come to appear misleading.
Comparable studies
Other randomized controlled trials on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
| Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. Adults with treatment-resistant depression | 2022 | Phase 2 double-blind randomized controlled trial | n = 233 |