Major depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression.

To assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder.

Based on data derived from a randomised clinical trial (N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction.

A time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight.

These data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.