Serial Ketamine Infusions as Adjunctive Therapy to Inpatient Care for Depression: The KARMA-Dep 2 Randomized Clinical...

Area of Science:

• Psychiatry
• Clinical Trials
• Pharmacology

Background:

• Serial ketamine infusions are increasingly used off-label for major depression.
• Evidence from placebo-controlled trials on ketamine's efficacy and safety is limited.

Purpose of the Study:

• To compare the antidepressant efficacy, safety, tolerability, cost-effectiveness, and quality of life of serial ketamine infusions versus midazolam.
• To evaluate ketamine as an adjunct to usual inpatient psychiatric care.

Main Methods:

• A double-blind, randomized, midazolam-controlled pragmatic trial (KARMA-Dep 2) involving hospitalized adults with major depressive episodes.
• Participants received up to 8 twice-weekly IV infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) alongside usual care, with a 6-month follow-up.

Main Results:

• No significant difference in depression symptom severity (MADRS scores) between ketamine and midazolam groups at the end of treatment.
• No significant between-group differences were observed in self-reported depression, safety, tolerability, cognition, cost-effectiveness, or quality of life.
• Most participants and raters correctly guessed their treatment allocation, suggesting a lack of blinding effectiveness.

Conclusions:

• Serial adjunctive ketamine infusions were not more effective than serial midazolam infusions for inpatients with major depression receiving standard psychiatric care.
• The findings suggest that ketamine may not offer superior benefits over midazolam in this clinical setting.
• Further research is needed to clarify the role of ketamine in managing major depressive episodes.