Low-Dose Buprenorphine Following Ketamine Treatment for Suicidal Ideation in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

This randomized, double-blind study examined whether low-dose buprenorphine could extend reductions in suicidal thoughts following ketamine treatment in adults with major depressive disorder. All 50 participants received one intravenous ketamine infusion, after which 45 completed enough follow-up to be included in the main analysis. Participants received either low-dose buprenorphine or a placebo for four weeks. Suicidal-thought scores decreased in both groups but improved more in the buprenorphine group. After four weeks, 78% of participants receiving buprenorphine and 48% receiving placebo had at least a 50% reduction in suicidal-thought scores. Overall depression symptoms improved in both groups, but the difference between the groups was not statistically significant. No serious treatment-related adverse events occurred, although dizziness, mouth irritation, headache, nausea, constipation, and dry mouth were reported. Some participants experienced increased suicidal thoughts and depression symptoms after buprenorphine was discontinued. Because the study was small, brief, conducted at one center, and excluded people with recent substance use disorders, larger and longer studies are needed to confirm the findings and evaluate long-term safety.

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