A more powerful ketamine (esketamine) nasal spray, combined with standard-of-care treatment, shows promise in quickly tamping-down depressive symptoms, according to results of a phase 2 study published April 16 in the American Journal of Psychiatry.

In a study of 68 patients randomly assigned to either esketamine or placebo with standard-of-care treatment, patients in the treatment group had a significantly greater improvement in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 hours’ and 24 hours’ follow-up after the first dose, reported Carla M. Canuso, MD, and her coauthors.

All patients voluntarily received standard-of-care treatment with hospitalization and antidepressants, noted Dr. Canuso, an employee of Janssen Research and Development, and her coauthors.

Esketamine, a more potent sibling of ketamine, is an N-methyl-D-aspartate receptor antagonist that modulates glutamatergic transmission. It is “being developed as an intranasal formulation for treatment-resistant depression and for rapid reduction of symptoms of major depressive disorder, including suicidal ideation, in patients at imminent risk for suicide,” Dr. Canuso and her coauthors reported.

MADRS scores were significantly improved in the esketamine group, compared with the placebo group, both 4 hours and 24 hours after initial dosing, but not at 25 days, Dr. Canuso and her colleagues reported. The esketamine group also had significantly greater improvement on the MADRS suicidal thoughts item 4 hours after first dose (P = .002), but not 24 hours after the first dose (P = .129) or at day 25 (P = .143).

The analysis also showed that, 4 hours after the first dose, 21.2% of participants in the esketamine group achieved resolution of suicide risk, compared with 9.7% for placebo patients. At 24 hours’ follow-up, 40% of esketamine patients and 6.5% of placebo patients had achieved resolution of suicide risk.

Serious adverse events (including suicidal ideation and suicide attempts) occurred in four participants in the esketamine group during the double-blind study phase. During the follow-up period, serious adverse events occurred in one patient in the treatment group and five patients in the placebo group. Other adverse events included nausea, dizziness, dysgeusia, and dissociation.

The results “may reflect a promising breakthrough in the clinical management of a potentially lethal condition for which there are no approved pharmacotherapies,” Dr. Canuso and her colleagues wrote. However, future research still is needed to evaluate the risk of dependence, they cautioned.

The study was funded by Janssen Research and Development.