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.
In a long-term extension study (SUSTAIN-3) involving 1,148 adults with treatment-resistant depression, esketamine nasal spray combined with an oral antidepressant was evaluated for safety and efficacy over up to 79 months (median 45.8 months). Common adverse events included headache (36.9%), dizziness (33.9%), and nausea (33.6%). Nine participants died, with causes including COVID-19 and suicide. Depressive symptoms, measured by the MADRS, improved during the initial induction phase (average reduction of 12.8 points) and this improvement was maintained during the optimization/maintenance phase. At the end of maintenance, 49.6% of participants were in remission. No new safety concerns emerged, and depression improvement generally persisted for those continuing treatment.