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Psilocybin Improves Treatment-Resistant Depression Regardless of Antidepressant Status

Jolynn Tumolo

Discontinuing antidepressants did not hamper the effect of synthetic psilocybin for treatment-resistant depression. Researchers reported the findings at the 2023 American Psychiatric Association Annual Meeting in San Francisco, California.

“We have not seen any evidence to suggest patients benefit from continuing on their antidepressants compared to those who withdraw before taking COMP360 psilocybin therapy,” presenter Guy Goodwin, MD, chief medical officer of COMPASS Pathway in London, said in the MedPage Today report. “While interesting, this finding will need replication and further evaluation in controlled trials.”

The findings stem from a phase 2b randomized controlled trial that found superior improvement in total Montgomery-Åsberg Depression Rating Scale (MADRS) score over 3 weeks with a 25-mg dose of the investigational psilocybin treatment COMP360 compared with a 1-mg dose. The analysis presented at this year’s conference was prompted by some previous studies that suggested selective serotonin reuptake inhibitor (SSRI) treatment may inhibit the effect of COMP360, a 5HT2A receptor agonist.

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The analysis included 233 participants who received a single dose of synthetic psilocybin amid a treatment-resistant major depressive episode. Participants had an average baseline MADRS score of 32.5.

Improvement in depression was similar among patients who withdrew from their antidepressant or antipsychotic treatment before psilocybin and those who continued, according to the coverage. MADRS scores decreased an average 12.2 for withdrawers and 11.8 for continuers with the 25-mg dose; 8.5 for withdrawers and 9.6 for continuers with the 10-mg dose; and 6.4 for withdrawers and 7.4 for continuers with the 1-mg dose.

Additionally, the analysis suggested that withdrawing from antidepressants before initiating treatment with psilocybin is safe. Among the two-thirds of participants who withdrew from antidepressant treatment 3 to 6 weeks prior to randomization, depression did not worsen.

 

Reference

Monaco K. Psilocybin Works just as well for depression with or without antidepressant. MedPage Today. May 25, 2023. Accessed June 5, 2023.

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