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.
David J Williamson, Jagadish P Gogate, Jennifer K Kern Sliwa, Lewis S Manera, Sheldon H Preskorn, Andrew Winokur, H Lynn Starr, Ella J Daly
The Journal of Clinical Psychiatry September 19, 2022 DOI: 10.4088/jcp.21m14318 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc analysis of 2 long-term phase 3 studies Longitudinal Peer reviewed |
|---|---|
| Sample size | 928 |
| Population | Patients with treatment-resistant major depressive disorder (per DSM-5) and nonresponse to at least 2 oral antidepressants |
| Interventions | Esketamine nasal spray oral antidepressant |
| Dose | 56 or 84 mg |
| Duration | 4-week induction phase (twice weekly), weekly for weeks 5-8, then weekly or every 2 weeks as maintenance treatment |
| Topics | Depression Esketamine |
| Registration | NCT02493868 NCT02497287 |
| Key points | Adverse events with esketamine nasal spray plus an oral antidepressant generally became less frequent with ongoing treatment, and most were mild or moderate in severity. Dizziness, dissociation, increased blood pressure, nausea, vertigo, and sedation were most common in week 1 and decreased thereafter; events occurring more frequently in week 1 were more likely to recur. |
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.
Comparable studies
Other observational and cohort studies on esketamine, most cited first.