Study shows psilocybin produces long-term antidepressant effects comparable to conventional antidepressants

A direct comparison between psilocybin, an experimental psychedelic drug, and a standard SSRI antidepressant shows similar improvement in depressive symptoms, but psilocybin offers additional longer-term benefits.

Comparing psilocybin (the active ingredient in “magic mushrooms”) with the SSRI escitalopram, the study found 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 journal Electronic clinical medicine to coincide with the conference presentation.

Lead researcher Dr Tommaso Barba (PhD student at Imperial College London) said: “This is the first work to compare the long-term effects of these two drugs in the context of general wellbeing, not just relief from depression. In previous work, we found that both treatments produced comparable improvements in relief of depressive symptoms after 6 weeks, such as sadness and negative emotions.

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

SSRI (selective serotonin reuptake inhibitor) medications, such as Prozac, Paxil, and Zoloft, are one of the main types of medications used to treat depression. However, about a third of patients do not respond to SSRI treatment, so psilocybin may be an alternative for them, although this was not studied in this trial.

Barba continued: “SSRIs work well, but not for everyone. They are also associated with some side effects. However, this work suggests that psilocybin generally appears to offer a real alternative, and perhaps additional benefits, to people who are wary of taking conventional antidepressants.”

Researchers at Imperial College London conducted a 6-month study (phase 2, double-blind randomized controlled trial) with 59 patients suffering from 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 about 20 hours in total.

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

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

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

The researchers note that patients were treated for only 6 weeks, and many patients received additional treatments during the 6-month follow-up.

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

Johan Lundberg (Assistant Professor of Psychiatry in the Department of Clinical Neuroscience at Karolinska Institutet in Stockholm), who was not involved in the work, said: “This report is an important attempt to compare the clinical value of psilocybin with a state-of-the-art treatment for major depressive disorder. The results have several caveats, including the lack of a non-inferiority analysis and the lack of reporting of other interventions administered during the follow-up period. That said, as a hypothesis-generating piece, it may be very beneficial to the field.”

“At this point, we don’t know whether psilocybin will be approved for the treatment of major depression, but if it is, it won’t be for everyone. Some future patients may prefer psychedelic treatment to SSRIs, but some patients may be intimidated by the dramatic alterations in perception and confrontations with difficult emotions that psychedelic drugs promote.”