A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
In an open-label retrospective analysis of 35 Veterans with co-occurring depression and PTSD, repeated intranasal (S)-ketamine treatments over four weeks were associated with reductions in both depression and PTSD symptoms. Depression scores on the PHQ-9 fell by an average of 5.1 points, from 19.8 to 14.7, with 14% of patients showing a clinically meaningful response. PTSD scores on the PCL-5 dropped by an average of 15.5 points, from 54.8 to 39.3, with 46% showing a clinically meaningful response. Changes in depression and PTSD symptoms were only moderately correlated, and some individuals experienced PTSD improvement without antidepressant response, suggesting distinct mechanisms of action for the two conditions.