This article presents the 6-month follow-up results of a phase 2, double-blind, randomized controlled trial comparing psilocybin therapy (PT) with escitalopram treatment (ET) for patients with moderate-to-severe major depressive disorder (MDD). A total of 59 patients (30 in the psilocybin group and 29 in the escitalopram group) were assessed using the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) as the primary outcome, alongside secondary measures of social functioning, connectedness, and meaning in life. Both PT and ET demonstrated sustained improvements in depressive symptom severity at the 6-month mark. However, PT showed greater benefits in social functioning (WSAS), psychological connectedness (WCS), and meaning in life (MLQ) compared to ET. Specifically, the between-group difference in WSAS at 6 months was −7.46, in WCS was 11.02, and in MLQ was 4.86, all statistically significant.

Patients in the PT group received two 25 mg doses of psilocybin with psychological support, while those in the ET group received escitalopram daily (10 mg for 3 weeks, increased to 20 mg for the next 3 weeks). At 6 months, both treatments showed large effect sizes for improvements in depression: PT had a mean QIDS-SR-16 reduction of 5.27 points (d = 1.33), and ET had a reduction of 6.83 points (d = 1.35). While there were no significant differences in the reduction of depressive symptoms between PT and ET, PT led to superior improvements in social functioning, connectedness, and meaning in life. At the 6-month mark, PT patients had significantly greater improvements in these secondary outcomes, including a 1.69 effect size improvement in social functioning, compared to 0.66 for ET.

Although both treatments appeared effective for depression, the PT group demonstrated greater improvements in psychosocial outcomes, which highlights the potential added value of psilocybin therapy beyond symptom reduction. No significant differences were reported regarding side effects or safety outcomes during the follow-up period, although 62.7% of patients received additional treatments such as psychotherapy or other medications during this time, which could have influenced the results. Despite the encouraging findings, limitations such as missing data and reliance on self-reported assessments mean the results should be interpreted with caution, and further research is needed to clarify the long-term benefits of psilocybin therapy.

In summary, this study suggests that both psilocybin and escitalopram are effective for treating depression over six months, but psilocybin therapy may offer added benefits in terms of social functioning and connectedness. These findings provide promising evidence for the integration of psilocybin in the treatment of MDD, though the reliance on additional post-trial interventions and missing data points necessitate further investigation to confirm these results.