In a real-world Spanish study of 189 adults with treatment-resistant depression, esketamine nasal spray led to response or remission in 80.4% of patients during the induction phase and 90% during the maintenance phase. Remission rates rose from 9.5% in induction to 38.3% in maintenance. Over a quarter of patients (28.0%) reported symptom improvement within 24 hours. Most adverse events were mild and decreased over time, especially in the first four weeks. The findings suggest esketamine nasal spray is an effective and safe option for treatment-resistant depression.
Ketamine can rapidly improve symptoms in adults with treatment-resistant depression, but its effects often last only a median of 2–4 weeks. This systematic review examined strategies to prolong ketamine's acute antidepressant effects. After searching PubMed/MEDLINE, 22 studies were included: 10 randomized controlled trials, 8 open-label trials, 1 retrospective chart review, and 3 case reports. No treatment modality—including pharmacological interventions, psychotherapies, electroconvulsive therapy, or transcranial magnetic stimulation—significantly prolonged the effects of intravenous ketamine, except for repeat-dose IV ketamine itself. Maintenance esketamine is effective in responders. More multimodality strategies are needed.