Serial Ketamine Infusions No Aid for Inpatient Major Depressive Episodes

WEDNESDAY, Nov. 5, 2025 (HealthDay News) — Serial adjunctive ketamine infusions are not more effective than serial midazolam infusions in reducing depressive symptoms in patients receiving inpatient psychiatric care for a major depressive episode, according to a study published online Oct. 22 in JAMA Psychiatry.

Ana Jelovac, Ph.D., from Trinity College Dublin and St. Patrick’s University Hospital, and colleagues assessed efficacy, safety, tolerability, cost-effectiveness, and quality of life for serial ketamine infusions (0.5 mg/kg) versus midazolam (0.045 mg/kg) as an adjunct to usual inpatient care. The analysis included 62 adults hospitalized with a major depressive episode (unipolar or bipolar).

The researchers found that end-of-treatment Montgomery-Åsberg Depression Rating Scale scores did not significantly differ between the ketamine and midazolam groups (adjusted mean difference, −3.16 points; 95 percent confidence interval, −8.54 to 2.22; P = 0.25; Cohen d, −0.29). There also was no significant between-group difference between Quick Inventory of Depressive Symptoms, Self-Report, scores (adjusted mean difference, −0.002; 95 percent confidence interval, −2.71 to 2.71; P > 0.99; Cohen d, −0.0004). For other secondary outcomes (e.g., cognition, cost-effectiveness, or quality of life), there were no significant between-group differences observed. Treatment allocation was accurately guessed by most patients and raters.

“Previous estimates of ketamine”s antidepressant efficacy may have been overstated, highlighting the need for recalibrated expectations in clinical practice,” lead author Declan McLoughlin, Ph.D., also from Trinity College Dublin, said in a statement.

Two authors disclosed ties to the pharmaceutical and biotechnology industries.

Abstract/Full Text