The international journal of neuropsychopharmacology
June 6, 2025
Naim Zaki, Li Nancy Chen, Rosanne Lane et al.
32 citations
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.
American Journal of Psychiatry
September 10, 2025
Gerard Sanacora, Muhammad Ahmed, Brianne Brown et al.
24 citations
Over nearly five years of real-world use in the United States, esketamine's safety profile remains consistent with clinical trial findings and product labeling. Among 58,483 patients completing 1,486,213 outpatient sessions, sedation occurred in 34.7% of sessions, dissociation in 41.0%, and increased blood pressure in 0.9%. Serious adverse events were rare, reported in less than 0.1% of sessions in the REMS program and 0.18% in the US-GMS database. Suicide rates were lower than background rates, and 210 incidences of all-cause abuse or misuse were reported. No new safety signals were identified.
The international journal of neuropsychopharmacology
December 1, 2024
Craig Chepke, Richard Shelton, Gerard Sanacora et al.
7 citations
Esketamine nasal spray, approved for treatment-resistant depression and major depressive disorder with suicidal thoughts, rarely causes respiratory depression after marketing. Analysis of 47 months of postapproval safety data found 50 cases of respiratory depression among patients, with 8 strongly linked to the drug. The estimated incidence is 1 case per 20,000 treatment sessions. Symptoms are manageable and resolve with minor support. Monitoring, including pulse oximetry, is recommended during postdose observation.