Explore This IssueDecember 2019
What are the long-term effects of esketamine nasal spray in patients with treatment-resistant depression (TRD)?
Bottom line: For patients with TRD who experienced remission or response after esketamine treatment, continuation of esketamine nasal spray in addition to oral antidepressant treatment resulted in clinically meaningful superiority in delaying relapse compared with antidepressant plus placebo.
Background: Depression is the leading cause of disability worldwide and is associated with a 10-year reduction in life expectancy. Patients with treatment-resistant major depressive disorder (MDD) experience relapse at a higher rate than do those with treatment-responsive MDD. In contrast to available data about short-term antidepressant effects of esketamine and ketamine, little is known about maintaining long-term antidepressant effects.
Study design: A multicenter, double-blind, randomized withdrawal study of 297 adults with prospectively confirmed TRD was conducted from Oct. 6, 2015, to Feb. 15, 2018.
Setting: A variety of academic and nonacademic clinic settings across the United States, Canada, and Europe.
Synopsis: Overall, among patients who achieved stable remission, 24 in the esketamine/antidepressant group and 39 in the antidepressant/placebo group experienced a relapse event during the maintenance phase; among patients who achieved a stable response (but not remission), 16 in the esketamine/antidepressant group and 34 in the antidepressant/placebo group experienced relapse. Continued treatment with esketamine and antidepressant significantly delayed and decreased relapse compared with treatment with antidepressant and placebo. The five most common adverse effects (AEs) reported in the esketamine/antidepressant group were dysgeusia, vertigo, dissociation, somnolence, and dizziness. Most AEs were mild to moderate, observed after dosing, and generally resolved in the same day. No deaths were reported. Serious AEs were reported for six esketamine/antidepressant patients (autonomic nervous system imbalance, disorientation, hypothermia, lacunar stroke, sedation, simple partial seizures, and suicidal ideation) during the induction phase. Transient blood pressure increases were observed with esketamine on treatment days and typically returned to the predose range by 1.5 hours after administration. Limitations included the fact that esketamine has known transient dissociative and sedative effects that are difficult to blind.
Citation: Daly EJ, Trivedi MH, Janik A, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression. A randomized clinical trial. JAMA Psychiatry. 2019;76:893–903.