Esketamine Nasal Spray Tolerability Trends During Post-Dose Monitoring in Patients With Treatment-Resistant Depression

Objective: This post hoc analysis assessed (1) whether the first-week incidence of adverse events (AEs) considered most commonly linked to the duration of the post-dose monitoring period predict recurrence of the same AEs over the following 3 weeks, and (2) whether the first-week clinician-judged time to readiness to leave clinical sites remained similar in duration to that observed during the following 3 weeks.

Methods: This post hoc analysis examined data from two 4-week, randomized, double-blind, active-controlled trials (fixed-dose study, NCT02417064; flexible-dose study, NCT02418585) comparing esketamine nasal spray (ESK) plus a newly initiated oral antidepressant with a newly initiated oral antidepressant plus placebo nasal spray (PBO) in treatment-resistant depression. Patients were dosed with ESK or PBO twice a week, monitored for ≥90 minutes post-dose, and assessed to determine their readiness to leave clinical sites.

Results: Of the AEs considered most relevant in determining readiness to leave, the reported events followed similar patterns. Dissociation, dizziness, vertigo, nausea, and somnolence were not evident in 77.7%, 76.5%, 82.9%, 79.7%, and 88.7% of subjects during the first week, respectively. These AEs occurred in fewer than 7% of these same participants over the following 3 weeks. When these AEs occurred during the first week, recurrence was more likely in future sessions. Time to readiness to leave clinical sites after dosing was similar to that seen during the first week of treatment.

Conclusion: Incidence of specific AEs in the monitoring period following dosing with ESK in the first week of treatment may predict recurrence during subsequent treatments.