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Michael Fulks MDNov 16, 2021 10:51:00 AM1 min read

Antidepressants or Magic Mushrooms: Which Works Best for Depression?

Major depression is a common and serious illness, affecting up to 10% of the population at any given time. Unfortunately, current antidepressants do not show mass improvements for depressive episodes.  Studies show that after two months of treatment, about one third of patients improve (similar to the effects seen in the placebo group of those same studies), while one third are left unchanged. Many patients also discontinue treatment either because of perceived futility or side effects.

There have long been advocates of psychedelic agents in the treatment of depression, but limited research is available in part because these drugs are Schedule 1 making such research onerous.  However, we now have two randomized trials of psilocybin (magic mushrooms), as detailed in the studies below. Psilocybin has known serotonergic and glutamatergic actions.

As published in NEJM, a UK trial compared psilocybin (2 doses) to escitalopram (an SSRI given daily), showing more favorable results for psilocybin. However, results were not significantly better for the primary measure because confidence intervals just barely overlapped. Unfortunately, fewer data points than expected were available due to COVID-19 issues leading to wider confidence intervals.  A US trial detailed in JAMA Psychiatry compared an immediate treatment group (2 doses of psilocybin) to a delayed treatment group, finding substantial and significant improvement in the treated group. In both studies, participants were monitored and provided psychological support during both days of psilocybin administration which was very well tolerated.

Psilocybin appears to improve depression, works promptly, and is well tolerated. It may work better than current antidepressants but that is not yet proven, and it will likely require monitoring and support during days of administration. These two studies in prominent journals suggest increasing interest and clear recognition that current therapies are inadequate and that an alternative approach may be available.

About the Author

Michael Fulks, MD, Consulting Medical Director, is board-certified in internal and insurance medicine. After leaving practice, he served as a medical director, creating or editing several underwriting manuals and preferred programs. For the past 8 years, Dr. Fulks has consulted for CRL, participating in its mortality research on individual tests and all laboratory test results, BP and build in combination. He is also involved in the development and implementation of automated screening tools for non-laboratory data.