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.
Patients with treatment-resistant depression who also have anxiety tend to respond less well to antidepressants. This analysis of existing trial data examined whether adding esketamine to an antidepressant improves outcomes for such patients. Among those with comorbid anxiety, the combination of esketamine and an antidepressant led to greater improvement in depressive symptoms compared to an antidepressant alone. The benefit was also seen in patients without anxiety, though the difference was less pronounced. The results suggest that esketamine augmentation may be particularly helpful for treatment-resistant depression patients who also struggle with anxiety.