Psilocybin therapy reduces depression in clinicians after pandemic frontline work

A randomized trial shows significant improvements in depression symptoms among healthcare workers using psilocybin, highlighting a potential breakthrough in mental health care.

Study: Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic. Image Credit: EliteExposure/Shutterstock.com

The COVID-19 pandemic severely impacted healthcare workers, causing widespread trauma and depression. A JAMA Network Open study explores psilocybin’s potential to relieve these symptoms in physicians and nurses.

Trauma and psilocybin

Healthcare workers faced significant trauma during the COVID-19 pandemic from multiple sources:

1. Personal Risk: Exposure to infection, illness, and death.
2. Family Concerns: Fear of infecting loved ones, leading to prolonged quarantine and isolation.
3. Increased Workloads: Coping with overwhelming demands without sufficient training or resources.
4. Emotional Toll: Witnessing severe suffering and multiple deaths, often in the absence of patients’ family members.

These challenges contributed to widespread post-traumatic stress disorder (PTSD), depression, and burnout among healthcare providers.

Psilocybin, when combined with psychotherapy, has shown promise in treating major depressive disorder and resistant depression. It has also reduced anxiety and stress in cancer patients facing end-of-life distress.

This randomized controlled trial (RCT) explores psilocybin’s potential to alleviate depression, burnout, and PTSD in healthcare workers who provided frontline care during the pandemic.

About the study

The investigators conducted a randomized controlled trial (RCT) from February to December 2022. It included 30 physicians, advanced practice practitioners (APPs), and nurses who had been on the frontline during the pandemic for one month or more. All but one were employed full-time at the study baseline.

Males and females were equally included, with the mean age being 38 years. All had been present or responded to a COVID-19 death, cared for a patient dying without family members present because of COVID-19-related health restrictions, had increased duty hours because of increased pandemic-related patient needs, or cared for a COVID-19 patient with critical illness.

All had sound mental health before the pandemic’s onset. At the study baseline, they suffered from moderate or severe depressive symptoms as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Interestingly, all had received counseling, and half had taken antidepressants.

Of the women, none were pregnant, and all had to use contraception during the trial. All had to reduce and eventually stop using antidepressants before the trial began. None had a family history of mental illness, and none used substances or had unstable medical conditions.

They were randomized to either a psilocybin 25 mg or niacin 100 mg group. The psilocybin arm was first given two preparation sessions to debrief from the pandemic and self-assess, as well as express the reasons for the medication session.

This was followed by the medication session with appropriate music. The integration sessions involved describing the medication experience and lessons learned, as well as practicing the lessons in future life.

Change in depressive symptoms

The researchers assessed changes in MADRS scores to track symptoms of depression. They also looked at possible changes in burnout and PTSD symptoms using the Stanford Professional Fulfillment Index [SPFI]) and Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]), respectively.

The MADRS scores indicated a mean change of -21.33 in depression scores from day 1 to day 28 in the psilocybin arm. In contrast, the drop was -9.33 in the niacin arm. The mean difference between the two arms was -12.

The improvement in depression symptoms within 28 days was maintained for at least six months. At this point, the average decrease was -24. This indicates a marked reduction in depressive symptoms, given the minimum relevant change of 1.6 to 1.9.

The SPFI scores did not show a significant improvement despite a numerically greater mean decrease in scores in the psilocybin arm. Due to this, the PCL-5 score was also assessed descriptively without examining its statistical significance.

This, too, showed a numerically greater decrease in PTSD symptoms in the psilocybin arm over the study period.

Serious toxicity or adverse events were absent. In the psilocybin group, about 27% had mild nausea or headache, while most had hypertension, either mild (40%), moderate (53%) or severe (7%). None required medical treatment.

Cognitive or perceptual distortions did not occur following the day of the medication session.

12 of the niacin group participants elected to take psilocybin therapy after the conclusion of the 28-day intervention period. They also showed a significant improvement in MADRS score over 28 days, at a mean change of -12.83.

Almost all participants changed jobs or institutions after the trial, with only 27% remaining in the same position and none leaving the field. This indicates the life-changing nature of the experiences during this trial.

The authors comment that the psilocybin-assisted therapy allowed participants “to feel all of their feelings, find some perspective on their recent past, and come to terms with what they were unable to do.”

This allowed them to return to finding meaning in their work while resolving unnecessary guilt and focusing on self, as well as other care.

Conclusion

“This randomized clinical trial found that psilocybin therapy resulted in a significant, sustained reduction in symptoms of depression experienced by clinicians after frontline work during the COVID-19 pandemic.”

Though both arms received the same counseling, psilocybin produced a much larger improvement. In contrast to earlier treatments, the psilocybin recipients registered a “rapid and sustained response.”

This new treatment paradigm for COVID-19-related depression deserves further validation studies to benefit clinicians with similar needs and challenges.