Since their introduction in the late 1980s, selective-serotonin reuptake inhibitors (SSRIs) have become the go-to treatment for major depression. SSRIs, however, have a number of limitations: they take several weeks to start working, can cause a variety of side-effects, and do not help some people with depression. A series of recent clinical investigations suggest that psilocybin, the active compound in magic mushrooms, may be an effective alternative. One question that these studies left unanswered, however, is how effective psilocybin treatment is compared to SSRIs.
In a first-of-its-kind study recently published in The New England Journal of Medicine, researchers at the Center for Psychedelic Research at Imperial College London compared psilocybin and escitalopram, an SSRI drug sold under the name Lexapro, as treatments for major depression. The six-week long study enrolled 59 volunteers with moderate-to-severe major depression. They were randomly and blindly assigned to receive treatment with psilocybin and an escitalopram control, or escitalopram and a psilocybin control. All the participants also received psychological support.
To evaluate the two treatments, the researchers compared the change from baseline on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16), a basic clinical measure of depression symptoms. Based on results of the QIDS-SR-16, psilocybin and escitalopram both reduce depression symptoms. The researchers did not detect a statistically significant difference between the two treatments.
The results of other measures taken in the study, however, suggest that psilocybin may be more effective than escitalopram. When designing the study, the researchers determined that the QIDS-SR-16 most directly addressed their experimental question and would therefore be the primary outcome measure, but they also evaluated depression symptoms with a number of additional scales. Nearly all secondary outcome measures favored psilocybin over escitalopram, but their results hold less weight than the QIDS-SR-16 because of how the study was designed.
The study was also limited by its small size, non-random enrollment of interested volunteers, and the possibility that participants may have been unblinded by the strong subjective effects of psilocybin or the well-known side-effects of SSRIs. Nonetheless, as the most rigorous evaluation of the therapeutic potential of psilocybin conducted to date, the results provide a benchmark for the design of future investigations.