Esketamine Nasal Spray for the Management of Treatment Resistant Depression in Adults: What is the Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed?

Introduction: Esketamine nasal spray for management of treatment-resistant depression (TRD) was assessed using the metrics of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

Methods: Analysis included four phase-3 randomized, double-blind studies (2 pivotal studies: acute flexible-dose; maintenance). Efficacy outcomes included acute response (Montgomery-Asberg Depression Rating Scale [MADRS] total score: ≥50% decrease from baseline), acute remission (MADRS≤12). NNT, NNH, LLH were calculated for esketamine nasal spray administered with a new oral antidepressant (esketamine+AD) vs AD+placebo in patients with TRD.

Results: Acute response for esketamine+AD (56-84 mg twice-weekly for 4 weeks) vs AD+placebo (rates 63.4% vs 49.5%, respectively) and remission (48.2% vs 30.3%) yielded NNTs of 8 and 6. For adverse events (AEs): dissociation (26.1% vs 3.7%), vertigo (26.1% vs 2.8%), nausea (26.1% vs 6.4%), dizziness (20.9% vs 4.6%), dysgeusia (24.3% vs 11.9%), the respective NNH values were 5, 5, 6, 7, and 9. Discontinuation rates due to AE (7.0% vs 0.9%) yielded NNH=17. LHH comparing remission vs. discontinuation due to AE was 17 vs 6, favoring esketamine+AD. Results were similar for other acute studies and pooled data. Maintenance use of esketamine (56-84 mg qw or q2w)+AD demonstrated NNT < 10 for relapse and maintenance of remission, and discontinuations due to AE (2.6% vs 2.1%) yielded NNH=178.

Conclusion: NNT < 10 for efficacy outcomes suggests potential benefit of esketamine+AD for both acute and maintenance use. LHH was favorable: esketamine+AD was 3x likely to result in acute remission vs discontinuations due to AE.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.