Ketamine infusions no better than midazolam infusions for inpatient depression treatment

Administering serial ketamine infusions does not show a clear advantage over serial midazolam infusions for reducing depressive symptoms in patients receiving standard inpatient psychiatric care, according to the KARMA-Dep 2 trial.

KARMA-Dep 2 included 65 hospitalized adults (mean age 53.5 years, 59.7 percent male) with a major depressive episode (unipolar or bipolar) and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥20.

The patients were randomly assigned to receive up to eight twice-weekly intravenous infusions of either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) as an adjunct to usual-care pharmacotherapy and other aspects of routine inpatient psychiatric care. All of them were followed-up for 6 months.

The primary outcome of depression symptom severity was assessed using observer-rated MADRS score from baseline to end of treatment. Secondary outcomes included self-reported depression severity, safety, tolerability, healthcare costs, and quality of life.

A total of 62 patients were included in the final analysis. End-of-treatment MADRS scores were not significantly different between the ketamine and midazolam groups (adjusted mean difference, −3.16 points, 95 percent confidence interval [CI], −8.54 to 2.22; p=0.25).

Likewise, self-reported depression severity at the end of treatment was comparable between the two groups (adjusted mean difference in Quick Inventory of Depressive Symptoms, Self-Report, scores, −0.002, 95 percent CI, −2.71 to 2.71; p>0.99).

Results for other outcomes showed no significant between-group differences.