A single intravenous dose of ketamine (0.5 mg/kg) rapidly reduced posttraumatic stress disorder (PTSD) symptom severity more than the active placebo midazolam in patients with chronic PTSD. Twenty-four hours after infusion, the ketamine group showed a mean reduction of 12.7 points on the Impact of Event Scale-Revised compared to midazolam. Ketamine also lessened comorbid depressive symptoms and improved overall clinical presentation. The treatment was generally well tolerated without persistent dissociative symptoms. These results suggest ketamine may offer a novel pharmacologic approach for chronic PTSD, though replication is needed.
In an open-label clinical trial, a single intravenous infusion of ketamine (0.5 mg/kg) was safe and well tolerated in 13 patients with mild cognitive impairment and major depressive disorder. No serious adverse events occurred. Depression severity, measured by the Montgomery-Asberg Depression Rating Scale, dropped from a mean of 27.4 before treatment to 5.7 at 24 hours after the infusion—a large-magnitude improvement. For 8 of the 13 patients, this improvement persisted for up to one month, with a mean score of 12.1 and at least a 50% reduction. These findings suggest ketamine may be effective for depression in this population, but larger randomized controlled trials are needed to confirm efficacy and assess cognitive effects.
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.