A 2-year extension of a clinical trial followed 183 adults with treatment-resistant depression who had been using esketamine nasal spray alongside an antidepressant. Over 136 weeks, 96.7% reported side effects, but 98.3% of those occurring on dosing days resolved the same day, and only 3.3% stopped treatment due to side effects. Among patients who achieved remission during the earlier phase, 79.2% did not relapse or discontinue treatment throughout the extension; the overall relapse rate for those reaching remission across both studies was 6.9%. No new safety concerns emerged, and the safety profile matched that seen in shorter-term studies.
Modern electroconvulsive therapy (ECT) and ketamine are the most effective treatments for depressed patients who do not respond to two or more antidepressants. Recent large head-to-head comparisons of intravenous ketamine versus ECT for treatment-resistant depression have produced conflicting findings, largely because of major differences in patients' baseline characteristics and treatment procedures across studies. This commentary argues that treatment decisions between ECT and ketamine should rely on predictive clinical response markers and patient preferences, not on direct comparisons that are methodologically limited. It also emphasizes that since ketamine is usually given before ECT, future studies should examine ECT's effectiveness specifically in patients who did not respond to ketamine.