A single infusion of ketamine, compared to midazolam as an active placebo, did not reduce suicidal ideation scores on the Beck Scale for Suicidal Ideation at 24 hours in patients with mood and anxiety disorders who were at elevated risk for suicidal behavior. A significant difference favoring ketamine emerged at 48 hours, but the effect was no longer significant by the end of 7 days. The intervention was well tolerated with no dropouts during the primary assessment period. The findings support the safety and tolerability of ketamine for suicidal ideation but larger studies are needed.
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.
Ketamine given intravenously at 0.5 mg/kg over 40 minutes was safe and well tolerated in a large group of patients with treatment-resistant depression. Across 205 infusions in 97 participants, the antidepressant response rate was 67%. Only about 2% of infusions were stopped due to adverse effects, and the overall dropout rate was 3%. Common temporary side effects in the first four hours included drowsiness, dizziness, poor coordination, blurred vision, and feeling strange or unreal. About one third of participants had changes in blood pressure or heart rate. There were small but significant increases in psychotomimetic and dissociative symptoms, but no lasting psychotic effects, medical complications, or increased substance use among those followed long-term.
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.