Janssen announced new findings from a Phase 2 study evaluating esketamine nasal spray in patients with major depressive disorder who were at imminent risk for suicide. The findings were published in the American Journal of Psychiatry.
Esketamine nasal spray is an investigational glutamate receptor modulator that is thought to help restore synpatic connections in brain cells in patients with major depressive disorder.
The double-blind, multicenter, proof-of-concept study randomized 68 patients to either esketamine nasal spray 84mg or placebo twice weekly for 4 weeks in addition to standard of care treatment. The primary efficacy endpoint was change from baseline to 4 hours post-dose on Day 1 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score; clinician global judgment of suicide risk (based on the Suicide Ideation and Behavior Assessment Tool) was also assessed.
Treatment with esketamine led to a statistically significant, clinically meaningful improvement in depressive symptoms at 4 hours, including a measure of suicidal ideation in study patients, compared to placebo.
Results showed that compared with placebo, treatment with esketamine led to a significantly greater improvement in MADRS total score 4 hours after the first dose (-13.4 for esketamine nasal spray + standard of care vs -9.1 for placebo nasal spray + standard of care (P=0.015). Significant improvement was also seen at ~24 hours (P=0.015; effect size = 0.65) but not at Day 25 (effect size = 0.35).
A significantly greater improvement on the MADRS suicidal thoughts item score was seen in patients treated with esketamine at 4 hours (effect size = 0.67) but not at 24 hours (effect size = 0.35) or Day 25 (effect size = 0.29). With regard to clinician global judgement of suicide risk scores, between-group reductions were not found to be statistically different at any time point.
Nausea, dizziness, dissociation, unpleasant taste, and headache were the most commonly reported adverse events associated with esketamine.
“This study begins to explore if esketamine can rapidly reduce depressive symptoms in acutely suicidal patients and bridge the gap of several weeks between when a patient begins a standard antidepressant and when that treatment begins to work. The results of this study reinforce the potential of esketamine as an acute treatment for patients in crisis,” said Carla Canuso, MD, Senior Director, Clinical Development, Janssen Research & Development, LLC.
If approved, esketamine has the potential to be the first treatment for patients with major depressive disorder at imminent risk for suicide.
For more information visit ajp.psychiatryonline.org.