Psilocybin as Effective as Traditional Antidepressants, With Added Benefits

A six-month follow-up study, from researchers at Imperial College London, found that psilocybin therapy not only alleviates depressive symptoms similarly to the selective serotonin reuptake inhibitor (SSRI) escitalopram but also provides additional benefits.

The findings, published in eClinicalMedicine, suggest that psilocybin may offer a more holistic alternative to traditional antidepressants, with fewer side effects and sustained mental health improvements.

The hunt for SSRI alternatives

An estimated five percent of adults suffer from depression, also referred to as major depressive disorder (MDD). This mental health condition can be highly debilitating for sufferers, leading to prolonged periods of low mood and a lack of interest in daily activities.

Traditional treatments for MDD include psychotherapy, often combined with pharmaceutical interventions such as antidepressants. SSRIs, like escitalopram, are among the most commonly prescribed drugs for depression. While SSRIs provide relief for many, around one-third of patients fail to respond to these treatments. Additionally, antidepressants can cause side effects such as sexual dysfunction, weight gain and fatigue, and they often take several weeks to become effective, highlighting the need for new treatment options.

Psychedelic treatment, such as psilocybin therapy, is being increasingly investigated as a rapid-acting alternative for treating MDD. Several clinical trials have demonstrated psilocybin's ability to produce almost immediate reductions in symptoms in patients with treatment-resistant depression.

In an earlier six-week trial, the researchers compared the effects of escitalopram and psilocybin in patients with MDD.

“In previous work, we had found that both treatments led to comparable improvements in alleviating symptoms of depression at the six-week mark, such as sadness and negative emotions,” said lead author Tommaso Barba, a PhD candidate at the centre for psychedelic research at Imperial College London.

While both treatment options showed similar overall reductions in depressive symptoms, psilocybin stood out by producing a greater decrease in anhedonia and leading to higher mood scores, suggesting it may offer advantages over SSRIs in certain areas. Barba's earlier study emphasized the need for further research to determine whether psilocybin's positive effects are sustained in the long term.

Psilocybin offers additional benefits

Barba and team conducted a six-month follow-up study on the patients in their previous trial. The initial investigation consisted of 59 participants with MDD who were split into 2 treatment groups:

1. Received 2 oral doses of 25mg of psilocybin 3 weeks apart, as well as daily placebo capsules.
2. Received 2 oral doses of 1mg of psilocybin 3 weeks apart, as well as daily pills of escitalopram 10–20 mg.

Each group received psychological support of around 20 hours in total during the 6-week trial. To assess the long-term impacts of psilocybin, compared to escitalopram, participants took monthly online questionnaires for six months post-study, which assessed several well-being characteristics as well as symptoms of depression.

Both treatment groups showed similar long-term improvements in depressive symptoms; however, patients taking psilocybin also reported enhanced psychosocial functioning, including a stronger sense of meaning in life and greater psychological connectedness.

“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," said Barba.

“Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work and social functioning. These results appeared to be maintained over a six-month follow-up period,” said Barba.

A real alternative to SSRIs

“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,” said Barba.

Although SSRIs are effective, their associated side effects can be a concern for many patients. The recent study highlights the potential of psilocybin as a real alternative to traditional antidepressants, while offering additional benefits.

“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,” said co-first author Dr. David Erritzoe, a clinical senior lecturer in general psychiatry in the centres for neuropsychopharmacology and psychedelic research at Imperial College London.

“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,” Erritzoe cautioned.

Reference: Erritzoe D, Barba T, Greenway KT, et al. 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. eClinicalMedicine. 2024. doi: 10.1016/j.eclinm.2024.102799

This article is a rework of a press release issued by the European College of Neuropsychopharmacology. Material has been edited for length and content.