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.
In adults with treatment-resistant depression, esketamine nasal spray combined with an oral antidepressant leads to higher remission rates than quetiapine extended-release combined with an oral antidepressant. Starting at week 8, 28.3% of esketamine-treated patients achieved remission compared to 18.6% on quetiapine, and by week 32, 55.7% versus 36.3%. Depressive symptoms improved more with esketamine from day 8 onward. Fewer patients stopped treatment due to side effects with esketamine (4.5%) than with quetiapine (10.1%). These results come from a secondary analysis of a randomized trial.
In adults with major depressive disorder and active suicidal ideation with intent who did not show early improvement, adding esketamine nasal spray to standard care increased the likelihood of achieving a response (63.9% vs 48.0%) and remission (35.1% vs 24.4%) after four weeks compared to placebo plus standard care. The odds of response were nearly double with esketamine. Similar benefits appeared for those who had not responded after one week. The findings suggest that continuing esketamine treatment for the full four weeks can be beneficial even when early response is absent.