Intranasal esketamine in treatment-resistant depression: long-term dosing patterns and clinical outcomes in a 5-year observational study.

Among 45 patients with treatment-resistant depression treated with intranasal esketamine alongside oral antidepressants in a routine clinic, depression severity scores dropped from an average of 40.0 to 22.9 at four weeks and to 9.70 at 52 weeks, with scores remaining near 9-10 at later follow-ups. Eight patients stopped treatment, mostly due to lack of efficacy or side effects. No manic symptoms emerged, and side-effect ratings were low. The findings suggest sustained symptom improvement and a favorable long-term safety profile for those who continued treatment, though the observational design, concurrent treatments, and survivor bias limit the conclusions.

Study at a glance

Abstract

Treatment-resistant depression (TRD) remains a major clinical challenge, and long-term real-world data on intranasal esketamine are limited. To describe long-term dosing patterns and clinical outcomes associated with intranasal esketamine in routine clinical practice. Single-center observational cohort study with descriptive analyses. We analyzed 45 patients with TRD treated with intranasal esketamine in a naturalistic setting, with follow-up extending up to 260 weeks. Esketamine was used adjunctively with ongoing oral antidepressants. Outcomes included the Montgomery-Åsberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Glasgow Antipsychotic Side-effect Scale (GASS). Treatment patterns were summarized using person-time (person-weeks). Baseline MADRS was 40.0 (SD 4.63). Mean MADRS decreased to 22.9 (SD 7.99) at week 4 and to 9.70 (SD 5.35) at week 52, with mean scores remaining around 9-10 at later time points among patients with available follow-up. Eight patients (17.8%) discontinued treatment (lack of efficacy n = 4; intolerable adverse effects n = 3; lost to follow-up n = 1). No treatment-emergent hypomania or manic symptoms were observed; YMRS scores decreased over time. GASS scores were low overall, with median values of 0 from week 13 onwards. In a real-world TRD cohort with complex comorbidities, intranasal esketamine used adjunctively was associated with sustained symptom improvement and a favorable long-term safety profile among patients who continued treatment, with dosing evolving from induction to individualized maintenance schedules. Findings are limited by the observational design, concomitant treatments, and survivor bias. Not applicable.