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.
In adults with treatment-resistant depression who had not responded to at least two prior oral antidepressants, esketamine nasal spray taken alone (without an oral antidepressant) reduced depressive symptoms more than a placebo. Over four weeks, both a 56 mg and an 84 mg dose of esketamine produced significantly greater improvements on the Montgomery-Åsberg Depression Rating Scale than placebo, with effects apparent as early as 24 hours after the first dose. Common side effects included nausea, dissociation, dizziness, and headache. The findings suggest that esketamine monotherapy could offer a new treatment option for patients who cannot tolerate or do not respond to oral antidepressants.
For patients with treatment-resistant depression, adjusting how often they use esketamine nasal spray based on their symptoms can help maintain or improve treatment response. In an open-label study of 778 patients, those who responded to twice-weekly esketamine during a 4-week induction phase then had their treatment frequency reduced to weekly. After four weeks of weekly treatment, 26% of 580 responders continued to improve, 50% maintained benefit, and 24% worsened. When frequency was further reduced to every other week, 19% improved, 49% maintained benefit, and 32% worsened. For patients who lost remission after reducing frequency, increasing back to weekly led to 47% improving, 43% staying the same, and 10% worsening. These results suggest that personalizing esketamine treatment frequency can optimize outcomes.