Psilocybin is as good as SSRI for depression, but doesn’t lower sex drive and gives a better sense of well-being and psychosocial functioning.
Researchers at Imperial College London compared the effects of psilocybin, the psychedelic compound in magic mushrooms, to the SSRI antidepressant escitalopram, finding both treatments effective for depression over six months. However, psilocybin patients reported better psychosocial outcomes, suggesting it could offer more comprehensive benefits for mental health, including enhanced life meaning and connectedness.
Psilocybin vs. SSRI Antidepressants
A head-to-head comparison of the experimental psychedelic drug psilocybin and conventional SSRI antidepressants reveals similar depressive symptom relief, with psilocybin providing extra long-term advantages.
The comparison, between psilocybin (the active ingredient in “magic mushrooms”) and the SSRI escitalopram gave similar long-term improvements in depressive symptoms over a 6-month period. However, patients taking psilocybin also reported better psychosocial functioning including experiencing 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 paper was published on September 21 in the peer-reviewed journal Lancet eClinicalMedicine to coincide with the conference presentation (see details below).
Long-Term Benefits and Well-Being Analysis
Lead researcher Mr. 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 well-being, not just freedom from depression. In previous work, we had found that both treatments led to comparable improvements in alleviating symptoms of depression at the 6-week mark, such as sadness and negative emotions. However, this work shows that psilocybin outperformed escitalopram in 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. In addition, in previous work we had found that psilocybin also improves sexual drive, in contrast to SSRIs which tend to lower libido in many patients. So overall it seems psilocybin might give additional positive mental health benefits.”
SSRI drugs (selective serotonin reuptake inhibitors), such as Prozac, Paxil, and Zoloft, are one of the main types of drugs used to treat depression. However, around a third of patients don’t respond to SSRI treatment, so for them psilocybin may offer an alternative, although this was not studied in this trial.
Comparative Study and Participant Insights
Tommaso Barba continued:
“SSRIs work well, but not for everyone. They are also associated with some side effects. However, this work implies that psilocybin generally seems to offer a real alternative, and perhaps additional benefits, to people who are worried about taking conventional antidepressants”.
The researchers, from Imperial College in London, undertook 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 were given a six-week course of escitalopram. Each group received similar psychological support of around 20 hours in total. Both groups showed significant improvement in depressive symptoms, even up to 6 months after treatment (the researchers stopped monitoring at 6 months). However, those given psilocybin reported greater improvements in social functioning and psychological connectedness, with large effect sizes.
Clinical Implications and Future Research Directions
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 improving connectedness and having greater meaning in life can significantly enhance a person’s quality of life and long-term mental health. The study suggests that psilocybin therapy might be a more holistic treatment option for depression, addressing both the symptoms of depression and overall well-being. This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment”.
The researchers note that the patients were only treated for 6 weeks, and that many of the patients received additional treatments over the 6-month follow-up.
Expert Opinions and Safety Considerations
Dr. Erritzoe cautioned:
“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 recreational psychedelic use, which is known for having unpredictable and potentially harmful effects, especially for vulnerable people struggling with mental health issues.”
Commenting, Johan Lundberg (Adjunct Professor of Psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm) said:
“This report is an important attempt to compare the clinical value of psilocybin compared to a state-of-the-art treatment of major depressive disorder. The results come with several caveats, including the lack of a non-inferiority analysis and failure to report other interventions given during the follow-up period. That said, as a hypothesis-generating piece it may benefit the field substantially. For now, we don’t know if psilocybin will be approved for the treatment of major depression, but if so, it won’t be for everyone. Some future patients might prefer psychedelic treatment over SSRI, but some patients may be intimidated by the dramatic alterations in perception and confrontations with challenging emotions that psychedelic drugs promote.”
This is an independent comment, Professor Lundberg was not involved in this work.
Reference: “Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial” by David Erritzoe, Tommaso Barba, Kyle T. Greenway, Roberta Murphy, Jonny Martell, Bruna Giribaldi, Christopher Timmermann, Ashleigh Murphy-Beiner, Michelle Baker Jones, David Nutt, Brandon Weiss and Robin Carhart-Harris, 21 September 2024, eClinicalMedicine.
DOI: 10.1016/j.eclinm.2024.102799
Meeting: 37th ECNP Congress