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Psilocybin May Improve Outcomes More Than Traditional MDD Treatments
While intensive treatments with psilocybin and the serotonin reuptake inhibitor (SSRI) escitalopram were associated with long-term improvements in major depressive disorder (MDD) symptom severity, recent phase 2 trial results published in eClinicalMedicine found that psilocybin leads to greater sustained improvements at 6-month follow-up. The study authors advised caution in interpreting the results due to potential limitations and emphasized the need for further investigation into the impact of adjunct treatments on study results.
“This is the first work to compare the long-term effects of these 2 drugs in the context of overall well-being, not just freedom from depression,” co-lead-author, Tommaso Barba, PhD candidate, Imperial College, London, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being in life, work, and social functioning.”
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The double-blind, randomized, controlled trial involved 59 patients with moderate-to-severe MDD, who were randomly assigned in a 1:1 ratio to either receive psilocybin therapy (PT) or escitalopram treatment (ET). The PT group received two 25-mg doses of psilocybin along with psychological support for 6 weeks while the ET group’s medication was administered daily at 10-mg for the first 3 weeks, and then increased to 20 mg for the following 3 weeks, along with matched support.
Of the 59 participants, 25 in the PT group and 21 in the ET group completed the 6-month follow-up. Both groups experienced sustained improvements in depressive symptom severity at the 6-month follow-up. However, there was no significant difference between the groups in depressive symptoms (mean Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) score difference of 1.51, p = 0.311).
Patients in the PT group demonstrated significantly greater improvements in social functioning (WSAS: −7.46; 95% CI: −12.4, −2.47; p < 0.001), psychological connectedness (WCS: 11.02; 95% CI: 1.25, 20.83; p = 0.033), and meaning in life (MLQ: 4.86; 95% CI: 0.67, 9.05; p = 0.021) at follow-up. These findings suggest that psilocybin therapy may offer broader psychosocial benefits beyond symptom reduction.
“Overall, the results suggest that although PT and ET may have comparable long-term effects in depression symptomatology, PT might be linked to sustained higher levels of global mental health beyond mere symptom reduction,” the authors wrote in the study.
The study results should be interpreted cautiously due to limitations such as the potential for missing data and reliance on self-reported treatment assessments, and the possible use of additional interventions during the follow-up period, researchers said.
Of the patients in the PT arm, 63% reported seeking additional treatment during the 6 months of follow-up. While there was “no observed disparity” in treatment uptake between the 2 groups, this still indicates a need for further investigation into the impact of adjunct treatments on the observed differences between conditions, authors said. The findings emphasize the importance of considering the influence of various treatment behaviors when interpreting the results and forming hypotheses.
Co-lead-author David Erritzoe, MD, PhD, MRCPsych, expressed, “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”.
“SSRIs work well, but not for everyone. They are also associated with some side effects,” Barba noted.
Adverse effects, including sexual dysfunction, weight gain, fatigue, and emotional blunting, are all associated with SSRIs. Consequently, non-adherence rates can reach as high as 50%.
“[T]his work implies that psilocybin generally seems to offer a real alternative, and perhaps additional benefits, to people who are worried about taking conventional antidepressants,” Barba said.
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