Spravato for suicidal veterans? What we know and don’t know

Meg Seymour, PhD: National Center for Health Research

Approximately 17 veterans commit suicide every day, and efforts by the Veterans’ Administration (VA) to reduce the epidemic have not been successful.1 In June 2019, President Trump responded to this crisis by urging the VA to provide a new antidepressant, Spravato, to any veteran that is depressed.2

What is Spravato?

Spravato is the brand name for esketamine, a nasal spray of a drug similar to ketamine, which is traditionally used as an anesthetic for surgery, but has also been tested as a depression treatment. In 2019, the FDA approved Spravato for treatment-resistant depression, but only if it is administered by a healthcare provider and combined with an antidepressant pill. Someone’s depression is considered treatment-resistant if they have tried antidepressant medications but have not sufficiently benefited from them. Spravato carries risks for side effects like dizziness, numbness, or feeling like the world is spinning.3

Is Spravato effective at preventing suicide?

FDA approved Spravato to treat depression, not to prevent suicide. They are not the same thing. There are several symptoms of depression besides feeling suicidal, and not all depressed people want to commit suicide. The manufacturer of Spravato only conducted one small study on the drug’s effectiveness in suicidal patients. They studied 66 patients who were admitted to an emergency room or inpatient psychiatric unit and who were considered an “imminent risk” of committing suicide. All patients were given an antidepressant pill, and half of the patients were randomly assigned to also take Spravato twice a week while the other half of patients were assigned to take a placebo twice a week. Researchers measured the severity of their depression over the course of 25 days. The severity of depression was measured by patients’ scores on the Montgomery-Asberg Depression Rating Scale (MADRS), which evaluates symptoms of depression, such as suicidal thoughts, difficulty concentrating, and sadness.4, 5 

Compared with patients given the placebo, the patients who took Spravato were less depressed (according to the MADRS) both 4 hours and 24 hours after receiving the drug. However, by day 25 of the study, there was no difference in depression between those given Spravato and those given a placebo. This could potentially mean that after a few weeks, when the antidepressant pills that patients were given started working effectively, Spravato no longer provided any added benefits. Since Spravato works more quickly as a nasal spray and had some benefit in the short-term, it could be used to help people who are very depressed as they wait for another antidepressant to work. However, the researchers did not consistently keep track of what types of antidepressant pills were given, and the study was small, so that makes it impossible to draw conclusions about how beneficial Spravato might be when given with specific other medications.

The patients in this study were in the hospital for the 25 days of the study, making it difficult for them to commit suicide even if they wanted to. Although Spravato’s manufacturer conducted other, larger studies, they were on patients with treatment-resistant depression, rather than on patients who were an immediate suicide risk. Even so, in those other studies, 3 patients who were given Spravato committed suicide, but no patients given a placebo committed suicide.

Would Spravato be effective at preventing veteran suicides?

Most of the veterans who commit suicide are men between the ages of 55 and 74.1 However, most patients in the Spravato study on suicidal patients were female, and all of them were under age 65. There is no way to know if the results would be better or worse for people over 65, or if it would be equally effective at helping prevent suicidal feelings in men compared to women. It is important to note that the studies of Spravato on patients with treatment-resistant depression (rather than suicidal patients) showed that Spravato was less effective for men than for women.

Not only is Spravato unproven to have any effectiveness at preventing veterans’ suicides, it is also an expensive drug. A VA committee declined President Trump’s urge for them to cover Spravato treatment for all veterans. We agree that this was “absolutely the correct decision,” given the small benefit for Spravato overall, and the lack of proof that the drug is effective for men or people over 65.

  1. U.S. Department of Veteran Affairs: 2019 National Veteran Suicide Prevention Annual Report. Washington, DC: U.S. Department of Veteran Affairs; 2019. https://www.mentalhealth.va.gov/docs/data-sheets/2019/2019_National_Veteran_Suicide_Prevention_Annual_Report_508.pdf
  2. U.S. Office of the Press Secretary. (2019, June 12). Remarks by President Trump in Meeting on Opioids, [Transcript]. Retrieved from https://www.whitehouse.gov/briefings-statements/remarks-president-trump-meeting-opioids/.
  3. U.S. Food and Drug Administration. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic. FDA.gov. https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified. March 5, 2019.
  4. US Food and Drug Administration. FDA Briefing Document: Psychopharmacologic Drugs Advisory Committee (PDAC) and Drug Safety and Risk Management (DSaRM) Advisory Committee Meeting. Silver Spring, MD: US Food and Drug Administration 2019. https://www.fda.gov/media/121376/download
  5. Montgomery, S.A. & Åsberg, M. (1979). Montgomery-Åsberg Depression Rating Scale (MADRS) [Measurement instrument]. Retrieved from http://narr.bmap.ucla.edu/docs/MADRS.pdf