In a year-long open-label study of 802 adults with treatment-resistant depression, esketamine nasal spray combined with a new oral antidepressant showed a manageable safety profile and sustained improvement in depressive symptoms. Common side effects included dizziness, dissociation, nausea, and headache, mostly mild or moderate and resolving the same day. Two deaths occurred, neither linked to the drug. Cognitive performance remained stable or improved. Depression scores dropped during the first four weeks and stayed lower through the maintenance phase.
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.
A single 84 mg dose of intranasal esketamine did not impair next-morning driving performance in patients with mild-to-moderate major depressive disorder or persistent depressive disorder, and same-day driving was not impaired after twice-weekly administration over three weeks. Alcohol, used as a positive control, significantly worsened driving (increased weaving by 1.83 cm), while esketamine showed no such effect. Twenty-seven patients completed on-road driving tests on a public highway. The findings suggest that esketamine, at this dose, does not compromise driving ability the morning after or on the same day of repeated use.