A single dose of ketamine, the anesthetic drug that has been found to have fast-acting antidepressant effects, can significantly reduce suicidal thoughts in patients with depression for up to a week, according to a new analysis.

The findings, published online October 3, 2017 in the American Journal of Psychiatry, come from data on 167 patients who participated in any of 10 previous studies on ketamine’s effects. All of the patients studied received a single dose of the drug or a control drug, administered intravenously. This “meta-analysis” – a study of multiple other studies – suggests that the drug not only reduces patients’ overall depression; it also appears to be particularly effective at countering suicidal thoughts.

Ketamine’s use as an antidepressant is experimental. Scientists have discovered that low doses of the drug can relieve symptoms of depression within hours. Because ketamine is an old drug and is no longer protected by patent, it is unlikely to be tested in large clinical trials that are required for FDA approval. But researchers note that it can be particularly effective as a rapid antidepressant and can rapidly reduce suicidal thinking. Multiple research efforts are devoted to inventing a ketamine-like drug that has its antidepressant potency but lacks its side effects.

In the current study, researchers led by 2016 Young Investigator Samuel T. Wilkinson, M.D., at Yale School of Medicine, collected and analyzed data from past studies with the goal of better understanding ketamine’s acute effects on patients who are experiencing significant thoughts of suicide. The research team also included grantees Michael H. Bloch, M.D., M.S., a 2013 and 2009 Young Investigator at Yale University; Sanjay J. Mathew, M.D., a 2009 Independent Investigator and 2006 and 2001 Young Investigator at Baylor College of Medicine; James W. Murrough, M.D., Ph.D., a 2009 Young Investigator at Icahn School of Medicine at Mount Sinai; Adriana Feder, M.D., a 2015 Independent Investigator and 2002 Young Investigator at Icahn School of Medicine at Mount Sinai; Carlos A. Zarate, Jr., M.D., the winner of the 2011 Bipolar Mood Disorders Award at the National Institute of Mental Health, a 2005 Independent Investigator and 1996 Young Investigator; and Gerard Sanacora, M.D., Ph.D., a 2014 Distinguished Investigator, 2007 Independent Investigator and a 2001 and 1999 Young Investigator at Yale School of Medicine.

Participants in the 10 studies included in the new analysis had been diagnosed with a range of psychiatric conditions, including major depression and bipolar disorder. Dr. Wilkinson and his colleagues focused on those participants who reported suicidal thoughts at the time of their trial. They analyzed ketamine’s effects upon both suicidal thoughts and scores on standard clinical depression scales, comparing patients’ responses to the drug to those of patients in control groups who received either saline or the anesthetic midazolam as a placebo.

The team found that both suicidal thoughts and overall depression were relieved significantly by ketamine; more than half were free of suicidal thoughts within 24 hours of their treatment. These benefits persisted for up to a week—the latest time point considered in the analysis.

Overall, those whose depression diminished the most experienced the greatest reductions in suicidal thoughts, but the researchers found that ketamine’s effects on suicidal ideation were significant even after controlling for changes in depression severity. This means the drug’s effects on this critical aspect of depression may be partially independent from its effects on mood, they say. This will undoubtedly be the focus of future research.