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.
A single intravenous dose of ketamine (0.5 mg/kg) produced rapid antidepressant effects in patients with treatment-resistant major depression, with 65% responding at 24 hours and 54% at 72 hours. Pretreatment with lamotrigine did not reduce ketamine's mild side effects or improve its antidepressant action. In a subsequent randomized trial, riluzole (100-200 mg/day) failed to prevent relapse over 32 days; 80% of riluzole-treated patients relapsed versus 50% on placebo, leading to early termination. Ketamine appears well-tolerated and rapidly effective, but better strategies to sustain its benefits are needed.
A review of 88 articles examined how ketamine is given (oral, intravenous, intranasal, subcutaneous) for treatment-resistant depression and chronic pain. The methodological quality of studies on ketamine's antidepressant effects was low for all routes. Doses used for depression were lower than those for pain. Studies on pain suggest that oral ketamine may be acceptable for depression in terms of tolerability and side-effects, but few studies have systematically examined longer-term negative consequences. The authors conclude that rigorous randomized controlled trials are needed to study short- and longer-term depression outcomes and side-effects.
A randomized placebo-controlled trial tested whether a fixed low dose of oral esketamine (30 mg three times daily) could reduce depression severity in patients with treatment-resistant depression. Over six weeks, the drug showed no benefit compared to placebo on the Hamilton Depression Rating Scale. Dizziness and sleep hallucinations were more common with esketamine. In an open-label extension phase where doses were individually titrated up to 3.0 mg/kg twice weekly, depressive symptoms decreased substantially. The findings suggest that fixed low-dose oral esketamine is ineffective, but individually adjusted higher doses may hold promise for treatment-resistant depression.
A triple-blind randomized placebo-controlled trial investigates daily oral esketamine versus placebo as an add-on to regular antidepressants in patients with treatment-resistant depression over 6 weeks, followed by a 4-week follow-up. This is the first such trial to examine the efficacy, safety, tolerability, mechanisms of action, and economic impact of repeated oral esketamine administration. If effective and tolerated, oral esketamine offers practical advantages over intravenous administration. The study aims to address the urgent need for additional treatment strategies for treatment-resistant depression.