The experimental drug esketamine rapidly reduced thoughts of suicide and symptoms of depression in a small clinical trial reported April 16 in the American Journal of Psychiatry.

Esketamine, like the closely related drug ketamine, is a drug with a long history of use as an anesthetic that has been found to significantly reduce depression symptoms within hours of treatment. In the newly reported trial, the drug was delivered via a nasal spray.

Traditional antidepressant medications, in contrast, may not become fully effective until a patient has taken them for four to six weeks.

The team, which included three members of the Foundation’s Scientific Council, tested esketamine’s effects in 68 patients, aged 19-64, with severe depression and considered at imminent risk of suicide. All participants in the trial were voluntarily hospitalized and received standard-of-care medications (one or more) for their depression. Importantly, all patients’ symptoms improved during the trial. But symptom reductions were greatest and most rapid among those who also received intranasal esketamine twice weekly, instead of a placebo.

Esketamine’s benefits were greatest early on. Four hours after participants’ initial treatment, suicidal thoughts and overall symptoms were significantly lower among those who had received esketamine compared to those who did not.

Treatment with esketamine and/or the standard-of-care drugs continued for four weeks, and patient follow-up continued eight weeks beyond that. By the end of the study, participants who had received the placebo had achieved similar reductions in depression and suicidal thoughts to those who received esketamine.

While a larger study is needed to more thoroughly evaluate esketamine’s safety and effectiveness, the findings suggest it could be valuable for managing severe depression and reducing suicide risk until traditional antidepressants can take effect.

The research team was led by BBRF Scientific Council members Husseini Manji, M.D., Wayne Drevets, M.D., and Gerard Sancora, M.D., Ph.D. The paper’s lead author was Carla M. Canuso, M.D., a 1998 Young Investigator. Dr. Manji, a 1998 Independent Investigator, was awarded the Falcone Prize (now Colvin Prize) for Outstanding Achievement in Affective Disorders Research in 1999; Dr. Drevets, a 1999 Independent Investigator and 1996 Young Investigator, was awarded the Colvin Prize in 2014. Dr. Sancora is a 2014 Distinguished Investigator, 2007 Independent Investigator, and 2001 and 1999 Young Investigator. Drs. Manji, Drevets and Canuso are affiliated with the pharmaceutical company Janssen, the study’s funder; Dr. Sancora, of Yale University, has been a Janssen consultant.