JAMA Network Open

Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic

Trial paperopen

Back, A., Baker, K. K., Freeman-Young, T. K., Gooley, T. A., Harvey, K., Kaelen, M., Kelmendi, B., Kollefrath, A., McGregor, B., Morgan, L., Myers, S., Sethi, T., Sorta, D., Tai, M., Thomas, B. J.

This double-blind randomised trial (n=30) finds that psilocybin therapy significantly reduces symptoms of depression in clinicians after frontline work during the COVID-19 pandemic. Psilocybin (25mg) showed greater reductions in depression (MADRS scores) and PTSD symptoms compared to the niacin control, though PTSD findings were not statistically significant.

Abstract

Objective To investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in US clinicians who developed these symptoms from frontline clinical work during the pandemic.Design, Setting, and Participants This double-blind randomized clinical trial enrolled participants from February to December 2022. Participants included physicians, APPs, and nurses who provided frontline care for more than 1 month during the pandemic and had no pre-pandemic mental health diagnoses but had moderate to severe symptoms of depression at enrollment. Participants were randomly assigned to either the psilocybin or niacin arm. Data analysis was conducted between December 2023 and May 2024 and was based on the intention-to-treat principle.Intervention One intervention episode consisted of 2 preparation visits, 1 medication session, and 2 integration visits. At the medication session, participants received psilocybin, 25 mg, or niacin, 100 mg, orally.Main Outcome and Measures The primary outcome was a change from baseline (preparation session 1) to day 28 (after medication administration) in symptoms of depression as measured by the clinician-administered Montgomery-Asberg Depression Rating Scale (MADRS) used by blinded raters. Secondary outcomes were changes in symptoms of burnout (measured with the Stanford Professional Fulfillment Index [SPFI]) and symptoms of PTSD (measured with the Posttraumatic Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]).Results A total of 30 clinicians (15 females [50%]; mean [range] age, 38 [29-60] years) were randomly assigned to receive psilocybin and 15 to receive niacin. The mean decrease in depression (MADRS scores) from preparation 1 session to day 28 was −9.33 (7.32) in the niacin arm, with a mean difference of −12.00 (95% CI, −17.67 to −6.33; P < .001), a decrease in MADRS scores significantly favoring psilocybin. The mean change in SPFI scores from preparation 1 session to day 28 was 1.00 (2.18) in the psilocybin arm vs −0.18 (1.98) in the niacin arm (mean difference, 1.18; P = .05) but was not statistically significant. While SPFI score change did not reach statistical significance, the PCL-5 score change was evaluated descriptively. The mean change in PCL-5 scores showed a numerically larger decrease in symptoms of PTSD from preparation 1 session to day 28 in the psilocybin vs the niacin arm (−16.67 [15.04] vs −6.73 [10.69]), but this difference was not statistically tested.