Long-term effectiveness and side-effects of intranasal esketamine in treatment-resistant depression: real-world, single-arm study of over 100 sessions

TL;DR

Intranasal esketamine shows long-term effectiveness in treating resistant depression with mostly mild side effects, but some urinary issues were observed.

Contribution

First real-world study evaluating esketamine over 100+ sessions in treatment-resistant depression.

Findings

PHQ-9 and GAD-7 scores significantly decreased after 129 sessions on average.

85% of patients improved in depression, and 65% in anxiety, with some achieving remission.

20% of patients experienced urinary symptoms, suggesting possible cystitis.

Abstract

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.

This study aimed to evaluate the long-term effectiveness and side-effects of intranasal esketamine in adults with TRD over more than 100 treatment sessions.

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

After an average of 129 esketamine sessions (mean duration 2.5 years), PHQ-9 and GAD-7 scores significantly decreased (P < 0.001). A total of 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. However, urinary symptoms suggestive of cystitis occurred in 20% of patients, highlighting the need for ongoing monitoring in long-term treatment.

Intranasal esketamine demonstrated sustained effectiveness and an acceptable side-effect profile 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.

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