Repeated intravenous esketamine treatment in patients with ECT-resistant major depressive disorder

Background: Ketamine is an anesthetic that appears to be an effective and rapidly acting pharmacological treatment in patients with Treatment-Resistant Depression (TRD). However, the definition of TRD varies greatly between published studies, and studies often did not include patients resistant to electroconvulsive therapy (ECT). Methods: We performed a chart study of 24 ECT-resistant TRD patients who received an open-label course of six esketamine infusions (0.5 mg/kg) over two weeks in the Leiden University Medical Center, Leiden, the Netherlands. Effectiveness was assessed with the Montgomery Åsberg Depression Rating Scale (MADRS) and the Inventory of Depressive Symptomatology (IDS-SR) up to four weeks after the last administration. Results: 23 (95.8%) patients (aged 48.7 ± 14.4 years, 79.2% female), completed the course. During treatment, eight patients (33.3%) achieved response (MADRS decrease ≥50%), five (20.8%) achieved remission (MADRS ≤10), and fourteen (58.3%) achieved a minimal clinically important difference (MADRS decrease >3 points). Relapse before or at follow-up occurred in 12.5%, 20% and 35.7% of these patients, respectively. An average decrease in MADRS scores of 9 points, and IDS-SR scores of 20 points, was observed. Limitations: This retrospective chart review permitted us only to use routinely collected open label and unblinded data. Conclusions: On average, intravenous esketamine demonstrated moderate to clinically meaningful effectiveness in this highly therapy resistant TRD patient population. However, results varied substantially between patients, from clinical deterioration to rapid remission. Despite the relatively lower remission rate compared with published data, a minimal clinically important difference was observed in over half of the patients.