Repeated intravenous infusions of ketamine, given over two weeks, significantly reduced symptom severity in chronic PTSD compared to a psychoactive placebo (midazolam). At two weeks, the ketamine group scored nearly 12 points lower on the Clinician-Administered PTSD Scale, and 67% of participants responded to treatment versus 20% in the placebo group. Among responders, the median time to loss of response was 27.5 days after the infusion course. Ketamine was well tolerated with no serious adverse events. This is the first randomized controlled trial to show efficacy of repeated ketamine infusions for chronic PTSD.
In a small randomized clinical trial, repeated doses of ketamine improved PTSD symptoms more than midazolam. Brain scans showed that symptom improvement was linked to increased communication between the ventromedial prefrontal cortex and amygdala when viewing emotional faces, especially in those who received ketamine. Ketamine-related improvement was also predicted by decreased activity in the dorsal anterior cingulate during emotional conflict and increased resting-state connectivity between the ventromedial prefrontal cortex and anterior insula. Further analysis indicated that ketamine specifically strengthened the prefrontal cortex's ability to inhibit amygdala responses to threatening social cues, suggesting a normalization of brain circuits involved in fear regulation.