Combination therapy shows promise in maintaining lower suicidal thoughts over time

New research published online today in the American Journal of Psychiatry finds that low-dose buprenorphine, given after a single ketamine infusion, significantly sustained reductions in suicidal ideation in adults with major depressive disorder. The randomized, double-blind, placebo-controlled trial is the first to show that a pharmacologic intervention may help maintain and build on ketamine's anti-suicidal effects in this at-risk population.

Ketamine is known to reduce suicidal thoughts very quickly, often within hours; however, its benefits usually do not last long. In the study, 50 adults with major depression and clinically significant suicidal ideation received a single open-label intravenous infusion of ketamine. Two days later, participants were randomly assigned to receive either low-dose buprenorphine or a placebo for four weeks. Forty-five participants completed at least one week of follow-on treatment and were included in the primary analysis. Both groups improved, but the buprenorphine group showed significantly greater reductions in suicidal ideation over time than the placebo group. At week four, there was a 76% reduction in suicidal ideation in the ketamine and buprenorphine group, compared to a 43% reduction in the ketamine and placebo group.

Depression scores improved in both groups during the study, but differences between groups were not statistically significant. No serious treatment-related adverse events occurred.

Two of the study's authors presented their findings at the Annual Meeting of the American Psychiatric Association. The findings are notable because there are currently no FDA-approved medications specifically indicated to reduce suicidal ideation in major depressive disorder. The authors conclude that the ketamine-buprenorphine sequence may represent a potentially scalable and safe therapeutic option for patients at risk of suicide.

Christine Yu Moutier, M.D., chief medical officer of the American Foundation for Suicide Prevention (AFSP), which was one of the study's funders, was also at the presentation to underscore the study's importance.

Christine Yu Moutier, M.D., Chief Medical Officer, American Foundation for Suicide PreventionThe Research Grants program at the American Foundation for Suicide Prevention began in the late 1980s at a time when there had been very little investment in research on suicide risk and prevention."

"Over the years, as AFSP has grown, our priority on funding research has helped to grow a mature field of suicide researchers, like Dr. Alan Schatzberg, who is a leader in the field and who mentors others. We are pleased with the results of his important study, one of the first to show the effectiveness of a pharmacologic intervention in helping maintain and build on ketamine's anti-suicidal effects in an at-risk population."

The authors noted that the study was relatively small and excluded individuals with substance use disorders, meaning additional research is needed to confirm the findings, determine optimal treatment duration, and better understand longer-term safety and effectiveness. They also note that further study is needed on tapering and follow-up strategies.

Source:

American Psychiatric Association

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