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Long-Term Effectiveness and Tolerability of Intranasal Esketamine in Treatment-Resistant Depression: A Real-World, Single-arm Study of Over 100 sessions

Nawfel Ayad, Samer Makhoul

European Psychiatry June 1, 2026 DOI: 10.1192/j.eurpsy.2026.10598 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Retrospective single-arm pre-post study Peer reviewed
Sample size 20
Population Adults with treatment-resistant depression at a private psychiatric clinic in the United Arab Emirates
Interventions Intranasal esketamine Oral antidepressants
Duration Mean 2.5 years, average 129 sessions
Measures Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7)
Topics Depression Esketamine
Key points After an average of 129 esketamine sessions (mean 2.5 years), PHQ-9 and GAD-7 scores significantly decreased (p<0.001). 85% improved in depressive severity (25% remission), 65% improved in anxiety severity (20% remission). Side effects were mild and transient, with no serious adverse events.

Abstract

Introduction: Treatment-resistant depression (TRD) poses a significant clinical challenge, with limited evidence guiding long-term pharmacological strategies. Esketamine, a glutamatergic modulator, has demonstrated short-term efficacy in TRD, but data on its extended use in real-world settings remains scarce Objectives This study aimed to evaluate the long-term effectiveness and tolerability of intranasal esketamine in adults with TRD over more than 100 treatment sessions.

Methods: We conducted a retrospective, single-arm pre-post study of 20 patients with TRD at a private psychiatric clinic in the United Arab Emirates. All participants received ≥100 sessions of intranasal esketamine alongside oral antidepressants. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. Tolerability was monitored through blood pressure, sedation, dissociation, urinary symptoms, and psychiatric side effects.

Results: After an average of 129 esketamine sessions (mean duration 2.5 years), PHQ-9 and GAD-7 scores significantly decreased (p<0.001). 85% of patients improved in depressive severity, with 25% achieving remission. 65% improved in anxiety severity, and 20% reached remission. Esketamine was generally well-tolerated; side effects were mild and transient, with no serious adverse events. No clinical or demographic factors significantly predicted response.

Conclusions: Intranasal esketamine demonstrated sustained effectiveness and acceptable tolerability in a real-world TRD cohort with extensive psychiatric comorbidity. These findings support its long-term use in complex clinical populations and underscore the need for further prospective, multi-site studies. Disclosure of Interest None Declared