Research shows that psilocybin has similar long-term antidepressant effects as standard antidepressants

A head-to-head comparison between the experimental psychedelic drug psilocybin and a standard SSRI antidepressant shows similar improvements in depressive symptoms, but psilocybin offers even greater long-term benefits.

The comparison between psilocybin (the active ingredient in ‘magic mushrooms’) and the SSRI escitalopram showed similar long-term improvements in depressive symptoms over a 6-month period. However, patients taking psilocybin also reported better psychosocial functioning, including a greater sense of meaning in life and psychological connectedness.

The work is presented for the first time at the ECNP Congress in Milan. A related article will appear in the magazine eClinical Medicine on the occasion of the presentation at the conference.

Lead researcher Tommaso Barba (PhD candidate from Imperial College, London) said: “This is the first work to compare the long-term effects of these two drugs in the context of overall wellbeing, not just freedom from depression. In previous work we had found that both treatments led to similar improvements in relieving symptoms of depression after 6 weeks, such as sadness and negative emotions.

“However, this work shows that psilocybin outperformed escitalopram across several measures of well-being, meaning in life, work and social functioning. These results appeared to be maintained over a 6-month follow-up period. Furthermore, we had found in previous work that psilocybin also improves sexual drive, unlike SSRIs which tend to decrease libido in many patients. So overall, it appears that psilocybin may provide additional positive mental health benefits.”

Selective serotonin reuptake inhibitors (SSRIs), such as Prozac, Paxil, and Zoloft, are one of the main classes of medications used to treat depression. However, about a third of patients do not respond to SSRI treatment, so for them psilocybin may offer an alternative, although this was not examined in this study.

Barba continued: “SSRIs work well, but they don’t work for everyone. They are also associated with some side effects. However, this work suggests that overall, psilocybin appears to offer a real alternative, and perhaps additional benefits, for people who are concerned about taking conventional antidepressants.”

The researchers from Imperial College London conducted a 6-month study (phase 2, double-blind, randomized controlled trial) with 59 patients with moderate to severe depression. 30 were treated with a single dose of psilocybin, 29 patients received a six-week course of escitalopram. Each group received similar psychological support for a total of about 20 hours.

Both groups showed significant improvements in depressive symptoms, even up to 6 months after treatment (researchers stopped monitoring after 6 months). However, those who received psilocybin reported greater improvements in social functioning and psychological connectedness, with large effect sizes.

Co-first author Dr David Erritzoe, Clinical Director and Deputy Head of the Centre for Psychedelic Research, Imperial College, London, commented: “This is important because greater connectedness and meaning in life can significantly improve a person’s quality of life and long-term mental health.

“The study suggests that psilocybin therapy could be a more holistic treatment option for depression, addressing both the symptoms of depression and overall well-being. This could make a substantial difference to the overall happiness and daily activities of people suffering from depression, providing a more cohesive approach to treating mental health.”

The researchers note that the patients were treated for only six weeks and many patients received additional treatments during the six-month follow-up.

Dr Erritzoe warned: “Psilocybin is still an experimental drug; it is not yet approved for general use. It is administered in very controlled and protected environments: these precautions are not found in recreational psychedelic use, which is known to have unpredictable and potentially harmful effects, particularly for vulnerable people struggling with mental health issues.”

Johan Lundberg (associate professor of psychiatry at the department of clinical neuroscience at the Karolinska Institute in Stockholm) was not involved in the work and said: “This paper is an important attempt to compare the clinical value of psilocybin with a state-of-the-art treatment for major depressive disorder. The results come with several caveats, including the lack of a non-inferiority analysis and the failure to report other interventions given during the follow-up period. That said, as a hypothesis-generating piece it could significantly benefit the field.

“We don’t know yet whether psilocybin will be approved for the treatment of major depression, but if it is, it won’t be for everyone. Some prospective patients may prefer psychedelic treatment over SSRIs, but some patients may be intimidated by the dramatic changes in perception and confrontations with challenging emotions that psychedelic drugs promote.”