Comparing Antidepressant Effects of Psilocybin-Assisted Psychotherapy in Individuals That Were Unmedicated at Initial Screening Versus Individuals Discontinuing Medications for Study Participation
- Author: mycolabadmin
- 3/25/2025
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Summary
This study compared how well psilocybin therapy works for people with treatment-resistant depression depending on whether they were already off antidepressants or had stopped taking them for the study. The researchers found that both groups improved similarly in depression and anxiety symptoms after receiving psilocybin with therapy support. These results suggest that stopping antidepressants before psilocybin treatment may not reduce its effectiveness, though more research is needed to fully understand the relationship between medication status and treatment outcomes.
Background
Treatment-resistant depression (TRD) affects approximately 30% of depression patients and requires novel therapeutic approaches. Psilocybin-assisted psychotherapy (PAP) has shown preliminary promise for treating depression. However, uncertainty exists regarding whether discontinuing antidepressant medications prior to PAP affects treatment efficacy.
Objective
To compare changes in depression, anxiety, and suicidality symptoms after a single 25 mg oral dose of psilocybin between treatment-resistant depression participants not on antidepressants at screening versus participants who discontinued antidepressant medications to receive PAP.
Results
No significant differences were found between MDC and UAS groups in clinician-rated depression (p=0.759), self-reported depression (p=0.215), anxiety (p=0.178), or suicidality (p=0.882) symptoms over time. Both groups demonstrated clinically significant improvements across all outcomes, with comparable intensity of psychedelic experience (p=0.191).
Conclusion
Comparable improvements in depression and anxiety symptoms were observed between antidepressant-discontinued and unmedicated patients receiving PAP. These findings contrast with some recent literature and contribute to growing evidence on medication tapering effects in psychedelic-assisted therapy. Further clinical research is needed to directly compare efficacy across medication statuses.
- Published in:Canadian Journal of Psychiatry,
- Study Type:Randomized Clinical Trial (exploratory post-hoc analysis),
- Source: PMID: 40129307, DOI: 10.1177/07067437251328316