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 a phase 3 trial across seven mood disorders centers in Australia and New Zealand, subcutaneous racemic ketamine was tested against midazolam for treatment-resistant depression. With flexible dosing (0.5–0.9 mg/kg), ketamine led to a 19.6% remission rate compared to 2.0% for midazolam, a significant difference. Fixed dosing (0.5 mg/kg) showed no difference. Acute side effects, such as psychotomimetic effects and blood pressure increases, resolved within two hours. The subcutaneous route proved practical and feasible.