PS222. Ketamine Exerts a Prolonged Reduction in Suicidal Ideation Independent of its Antidepressant Effects

Abstract Background: Subanaesthetic doses of intravenous ketamine have been shown to elicit rapid reduction in depressive symptoms and severity of suicidal ideation (SI). However, the antidepressant properties of ketamine appear to be transient. Repeated ketamine infusions may prolong the antidepressant effect. The objective of this study was to determine whether ketamine could elicit decrease in SI even in patients who do not have a reduction in depressive symptoms with prolonged treatment. Methods: 19 patients with treatment-resistant major depressive disorder (MDD) completed a randomized controlled trial of ketamine. Patients received 7 intravenous ketamine infusions during the study, including a single infusion during the Phase 1 double-blind crossover with midazolam (used as an active placebo), and 6 ketamine infusions administered over a two-week period during Phase 2. The primary outcome measures were pre- and post-treatment changes in depressive symptoms (using the Montgomery-Asberg Depression Rating Scale [MADRS]) and suicidal ideation (using MADRS-SI scores). Results: Patients with a 50% decrease in total MADRS scores from pre- to post-treatment were considered ketamine responders. Responders (n = 10) had a larger reduction in MADRS scores (62%) compared to nonresponders (n = 9; 17%) (p<0.001). Both groups had significant reductions in MADRS-SI scores (responders -1.9, p<0.001; nonresponders -1.6, p<0.001) and the difference in the magnitude of change in MADRS-SI scores between groups was not statistically significant (p=0.44). Conclusions: Ketamine had a direct effect on lessening suicidal ideation even in patients who failed to show a reduction in depression severity with repeated infusions.