Esketamine nasal spray compassionate use program in the Netherlands: An open label, multi-center cohort study in severe treatment-resistant depression

• Intranasal esketamine is an effective augmentation strategy for severe depression. • Intranasal esketamine showed significant improvement after 28 days. • Level of treatment resistance did not influence esketamine efficacy. Esketamine, a N-methyl- d -aspartate (NMDA) receptor antagonist, used intranasally (IN), is applied as an antidepressant (AD) in treatment-resistant depressed (TRD) patients. Real-world studies with IN esketamine are still scarce. To evaluate the effectiveness and potential moderators of response of IN esketamine in real-world TRD patients treated in a compassionate use program (CUP) in the Netherlands. In this multi-center, open label, naturalistic cohort-study 42 patients were treated with 28–84 mg IN esketamine augmenting an oral AD. We used the Montgomery-Asberg rating scale (MADRS) change scores as primary outcome and report response-, remission rates and minimal clinically important difference (MCID) reached after 28 and 90 days of treatment. Potential effect moderators studied were level of treatment resistance and history of electroconvulsive therapy (ECT). Baseline mean MADRS score was 33.6 ± 5.3 and 64.3 % of the population had a history of ≥5 failed AD treatments. At 28 days, a significant decrease of 10.1 (7.3–12.6) MADRS-points was observed (Cohen's d 1.9, 95 % CI: 0.26–0.45, t = 7.20, p < .001). Between 29 and 90 days no additional significant decrease in the MADRS score was observed. Response- and remission rates were 28.6 % and 14.3 % at 28 days and 35.7 % and 19.8 % at 90 days ( n = 42), respectively. At 28 days 52.4 % achieved MCID. No clinically relevant moderating effects were found. Small sample size and variable time between screening and start of treatment. In this group of TRD patients, IN esketamine treatment showed significant effectiveness, suggesting a valuable treatment option for this group.