Safety and effectiveness of intranasal esketamine for treatment-resistant depression: a real-world retrospective study

Introduction

Major depressive disorder (MDD) is common and a leading cause of disability. A substantial subgroup—treatment-resistant depression (TRD)—is conventionally defined as failure to respond to at least two adequate antidepressant trials and accounts for about one third of MDD cases, contributing disproportionately to the disease burden. Existing pharmacological and somatic treatments (switching or combining antidepressants, augmentation strategies, electroconvulsive therapy, transcranial magnetic stimulation, vagal nerve stimulation, deep brain stimulation) have limitations including delayed onset, high cost, procedural risk or limited evidence for TRD, leaving an unmet need for rapid-acting, tolerable therapies. Ketamine and its S-enantiomer esketamine have mechanistic plausibility for rapid antidepressant effects and esketamine nasal spray received FDA approval in 2019 on the basis of Phase III trials demonstrating faster onset and relapse-prevention effects under a Risk Evaluation and Mitigation Strategies (REMS) programme that mandates clinic-based administration and post-dose monitoring. Brendle and colleagues note that patients treated in routine clinical practice may differ from clinical trial samples in symptom severity, comorbidity and treatment schedules, so real-world safety and effectiveness data are limited. The present study set out to characterise the demographic and clinical profile, treatment patterns, clinical outcomes (depression, anxiety, suicidal ideation) and adverse events among adults with TRD receiving intranasal esketamine at a private outpatient integrative psychiatric clinic between July 2019 and June 2021, using retrospective electronic health record (EHR) data.