Buprenorphine After Ketamine for Suicidal Ideation in MDD

Key Takeaways

• Greater improvement in SSI total score was observed with buprenorphine than with placebo after ketamine.
• Depression scores did not differ significantly between groups.
• No serious treatment-related adverse events were reported.

In a randomized, double-blind, placebo-controlled trial, low-dose sublingual buprenorphine started after ketamine was associated with greater improvement in suicidal ideation than placebo among adults with major depressive disorder and suicidal ideation. The between-group effect size was Glass delta 0.76, with a 95% confidence interval from 0.11 to 1.39.

The trial evaluated whether low-dose buprenorphine could sustain or enhance ketamine’s antisuicidal effect after the initial infusion. The study was conducted at a single outpatient center in the United States in adults with major depressive disorder and a Scale for Suicide Ideation total score of at least 6. Participants were randomly assigned 1:1 to sublingual buprenorphine 0.2 to 0.8 mg/day or matched placebo for 4 weeks, and 68% were female. All participants first received a single open-label intravenous ketamine infusion of 0.5 mg/kg over 40 minutes; they started buprenorphine 48 hours later. The primary outcome was change in SSI total score assessed weekly from day 1 through day 31.

From November 2020 to March 2025, 50 participants received ketamine, and 45 completed at least 1 week of follow-on treatment. Mean SSI change was -11.6 in the buprenorphine group, with an SD of 5.8 and n=23, versus -6.3 in the placebo group, with an SD of 7 and n=22. Mixed-effects modeling showed a significant time-by-treatment interaction, with p<0.001. Across the weekly assessment period, suicidal ideation improved more with buprenorphine than with placebo.

Depression scores did not differ significantly between groups. No serious treatment-related adverse events were reported, and the abstract did not provide a fuller adverse-event breakdown.