New esketamine nasal spray improves suicidal thoughts and symptoms of depression

Positive results have emerged from the two pivotal Phase 3 clinical studies (ASPIRE I &II) that evaluated efficacy and safety of SPRAVATOTM (esketamine) CIII nasal spray combined with a comprehensive standard of care for the patients with major depressive disorder having active thoughts about suicide.

The results were announced by The Janssen Pharmaceutical Companies of Johnson & Johnson during the 32^nd European College of Neuropsychopharmacology (ECNP) held from Sept. 7-10, 2019 in Copenhagen. According to which, intranasal esketamine compared with placebo, given in addition to comprehensive standard-of-care treatment, may result in significantly rapid improvement in depressive symptoms, including some measures of suicidal ideation, among depressed patients at imminent risk for suicide.

"These data are particularly important because patients with major depressive disorder presenting with active suicidal ideation with intent constitute a psychiatric emergency that requires immediate intervention," Carla Canuso, Senior Director, Clinical Research, Janssen Research & Development, said in a press release. "Although currently available antidepressants are effective for many patients, their onset of effect can take four to six weeks, offering limited benefit to those in urgent need."

In the study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4 weeks, in addition to comprehensive standard-of-care treatment.

The primary efficacy endpoint was a change in score from baseline to 4 hours after the initial dose on the Montgomery-Åsberg Depression Rating Scale (MADRS). Clinician global judgment of suicide risk (from the Suicide Ideation and Behavior Assessment Tool) was also assessed. Secondary endpoints included these measures at 24 hours and double-blind endpoint at day 25.

Key findings include:

• A significantly greater improvement in MADRS score was observed in the esketamine group compared with the placebo group at 4 hours (least-square mean difference=25.3, SE=2.10; effect size=0.61) and at∼24 hours (least-square mean difference=27.2, SE=2.85; effect size=0.65), but not at day 25 (least-square mean difference=24.5, SE=3.14; effect size=0.35).


• Significantly greater improvement was also observed in the esketamine group on the MADRS suicidal thoughts item score at 4 hours (effect size=0.67), but not at 24 hours (effect size=0.35) or at day 25 (effect size=0.29).


• Between-group reductions in clinician global judgment of suicide risk scores were not statistically different at any time point.


• The most common adverse events among participants in the esketamine group were nausea, dizziness, dissociation, unpleasant taste, and headache.

"The results of this proof-of-concept study support the hypothesis that intranasal esketamine may be an efficacious treatment for rapid reduction of depressive symptoms, including suicidal ideation, in patients assessed to be at imminent risk for suicide. These findings may reflect a promising breakthrough in the clinical management of a potentially lethal condition for which there are no approved pharmacotherapies," concluded the authors.