Highlights:

• The standard ketamine dose-treated depression significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration.
• Involved 158 veterans and service members with treatment-resistant PTSD that failed prior antidepressant treatments in the past.
• Veterans were divided into a placebo group, and 2 separate ketamine treatment groups; a low dose group (0.2mg/kg), and a standard dose group (0.5mg/kg).

Results and Conclusions:

• The primary outcome measure was the self-report PTSD Checklist forDSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS).
• The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration.
• There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability.

This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects.