Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression.

ABSTRACT

Objective: To describe the tolerability of esketamine nasal spray based on the adverse event profile observed during treatment sessions occurring early and later over the course of treatment.Methods: In 2 long-term, phase 3 studies (NCT02493868, October 1, 2015-February 16, 2018; NCT02497287, September 30, 2015-October 28, 2017), patients with treatment-resistant major depressive disorder (per DSM-5) and nonresponse to ≥ 2 oral antidepressants received esketamine nasal spray (56 or 84 mg) twice weekly during a 4-week induction phase, weekly for weeks 5-8, and weekly or every 2 weeks thereafter as maintenance treatment, in conjunction with a new oral antidepressant. A post hoc analysis using descriptive statistics evaluated occurrence (incidence, frequency, severity) and recurrence (incidence and severity) of events of specific interest.Results: In patients treated with esketamine nasal spray plus a newly initiated oral antidepressant (n = 928), spontaneously reported adverse events of dizziness, nausea, sedation, vertigo, and increased blood pressure were more likely to recur after the first week of treatment if they occurred more frequently (twice > once > none) during the first week. The same pattern was observed when these events were assessed by structured instruments. Incidences of dizziness, dissociation, increased blood pressure, nausea, vertigo, and sedation were highest in week 1 of treatment (20.6%, 16.7%, 4.3%, 14.0%, 12.1%, and 3.8%, respectively) and decreased thereafter. Initial occurrences and subsequent recurrences of events were mostly mild or moderate in severity.Conclusions: Adverse events during treatment with esketamine nasal spray plus an oral antidepressant generally become less frequent with ongoing treatment, and the majority are mild or moderate in severity.Trial Registration ClinicalTrials.gov identifiers NCT02493868; NCT02497287.