Ketamine outperforms sedative for suicidal thoughts in major depression
Adjunctive ketamine demonstrated a greater and rapid reduction in suicidal thoughts among patients with major depressive disorder within 24 hours compared with midazolam, according to new study results.
"Currently available antidepressants can be effective in reducing suicidal thoughts in patients with depression, but they can take weeks to have an effect,” Michael Grunebaum, MD, research psychiatrist at Columbia University Medical Center, said in a press release. “Suicidal, depressed patients need treatments that are rapidly effective in reducing suicidal thoughts when they are at highest risk. Currently, there is no such treatment for rapid relief of suicidal thoughts in depressed patients."
In their randomized clinical trial, researchers examined the acute effect of adjunctive subanesthetic IV ketamine and the sedative midazolam on clinically significant suicidal thoughts in 80 adults with major depression. All participants scored 4 or higher on the Scale for Suicidal Ideation (SSI) and 43 were taking antidepressant medication. They randomly assigned participants to receive 0.5 mg/kg ketamine or 0.02 mg/kg midazolam in 100 mL saline infusion and measured SSI score 24 hours after infusion.
Within 24 hours, ketamine demonstrated a clinically significant reduction in suicidal thoughts in patients with major depression that was greater than with midazolam. Analysis showed that for the ketamine group, the reduction in SSI score was 4.96 points greater than in the midazolam group (95% CI, 2.33-7.59). The proportion of patients with a 50% or higher reduction in SSI score at day 1 was 55% for the ketamine group and 30% for the midazolam group (OR = 2.85; 95% CI 1.14-7.15.)
“I believe the importance and take-home message of this research is twofold: First, it provides evidence supporting a treatment for rapid relief of suicidal ideation in depressed patients where there has been an absence of any comparable intervention,” Grunebaum told Healio Psychiatry. “Second, it adds to work pointing towards a pathway to develop new antidepressant treatments that act by a novel mechanism and that may help the approximately one-third of patients who don’t respond to currently available antidepressant medications.”
Additionally, those who received ketamine had greater improvement in overall mood, depression and fatigue compared with those assigned to midazolam. Furthermore, patients maintained clinical improvement in suicidal thoughts for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up. Adverse effects were short-lived and typically resolved within minutes to hours after receiving ketamine.
"This study shows that ketamine offers promise as a rapidly acting treatment for reducing suicidal thoughts in patients with depression," Grunebaum said in the release. "Additional research to evaluate ketamine's antidepressant and anti-suicidal effects may pave the way for the development of new antidepressant medications that are faster acting and have the potential to help individuals who do not respond to currently available treatments." – by Savannah Demko
Disclosures: Grunebaum reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.