For adults with treatment-resistant depression who achieved stable remission or response after 16 weeks of esketamine nasal spray plus an oral antidepressant, continuing esketamine plus the antidepressant delayed relapse significantly more than switching to placebo plus the antidepressant. Among those in stable remission, 26.7% relapsed on esketamine versus 45.3% on placebo, a 51% reduction in relapse risk. Among stable responders, 25.8% relapsed on esketamine versus 57.6% on placebo, a 70% reduction. Common side effects of esketamine included transient taste disturbance, vertigo, dissociation, drowsiness, and dizziness.
Patients with treatment-resistant unipolar major depressive disorder who qualified for the RECOVER trial—the largest randomized sham-controlled study of vagus nerve stimulation for a psychiatric condition—had severe disability, a median of 11.0 prior failed antidepressant treatments, and high rates of suicidality (77% with suicidal ideation, 40% with previous suicide attempts). Seventy-one percent had received at least one prior interventional psychiatric treatment (electroconvulsive therapy, transcranial magnetic stimulation, or esketamine). Compared to those without such history, recipients of interventional treatments were younger, more severely depressed, had greater suicidal ideation, earlier onset of depression, and more failed medication trials.