• Psychiatry Clinical Trials
• Mood Disorders

• Psychiatry
• Psychiatry Clinical Trials
• Mood Disorders

Data from a randomized clinical trial show that patients with moderate to severe depressive symptoms treated with a single dose of ketamine show rapid improvement of depressive symptoms compared to patients treated with a psychoactive placebo control.

Sanjay J. Mathew, MD, Baylor College of Medicine, Houston, Texas, USA, and Michael E. Debakey, VA Medical Center, Houston, Texas, USA, reported on outcomes of the Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial [Murrough JA et al. Am J Psychiatry 2013], a two-site, parallel-arm, double-blind, randomized controlled trial that evaluated the rapid antidepressant efficacy of ketamine compared with an active placebo control (ie, midazolam) in patients with treatment-resistant major depression.

The study included patients with a primary diagnosis of major depressive disorder randomized in a 2:1 ratio to a single intravenous infusion of ketamine (0.5 mg/kg; n=47) or midazolam (0.045 mg/kg; n=25) between November 2010 and August 2012. Patient characteristics and demographics were similar between the two groups, with all patients showing chronic, treatment-resistant depression with moderate to severe symptom severity.

An anesthesiologist administered the 40-minute infusion and monitored continuous vital signs throughout the infusion. After 24 hours, all patients were discharged and sent home. They then were followed at 2, 3, and 7 days. At Day 7, patients who did not respond to treatment resumed prior treatment. Patients who did respond were invited to participate in a follow-up exploratory phase of the trial for an additional 4 weeks.

The primary outcome of the study was change in depression severity 24 hours after drug administration based on the clinically administered Montgomery-Asberg Depression Rating Scale (MADRS). Nonresponders were defined as patients with <50% improvement from baseline in the score on the MADRS.

At 24 hours, the researchers found that patients treated with ketamine had a significant reduction in depressive symptoms compared with those treated with midazolam based on the MADRS score that was 7.95 points lower in the ketamine group (mean 14.77 vs 22.72; p≤0.0014). Patients in the ketamine group were also more likely to have a response at 24 hours compared with the midazolam group (64% vs 28%; p≤0.006).

Dr. Mathew highlighted that among the significant improvements in depressive symptoms in the ketamine group, improvements in the inability to feel and lassitude were particularly robust.

The study also found that the patients who responded to ketamine generally maintained improvement in depressive symptoms for several days beyond the initial 24 hours.

At Day 7, 21 patients who had responded to ketamine and 4 who had responded to midazolam participated in an exploratory phase of the trial that looked at time to relapse in these patients given a single infusion of ketamine or midazolam. These results also showed a more durable benefit in the ketamine group.

According to Dr. Mathew, secondary analyses of these data are under way. Results of one study on the impact of ketamine on suicidal ideation showed a reduction in suicidal thoughts with ketamine versus midazolam [Price RB et al. Depress Anxiety 2014].

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