Long-term effectiveness and side-effects of intranasal esketamine in treatment-resistant depression: real-world, single-arm study of over 100 sessions.
Nawfel Ayad, Karim Abdel Aziz, Samer Makhoul, Ban Abbas, Syed Fahad Javaid
BJPsych Open January 23, 2026 DOI: 10.1192/bjo.2025.10950 (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 psychiatric out-patient clinic in the United Arab Emirates |
| Interventions | intranasal esketamine oral antidepressants |
| Duration | Average 2.5 years (mean 129 sessions) |
| Topics | Depression Esketamine |
| Keywords | Long-term effectiveness Maintenance therapy Real-world evidence |
| Citations | 2 |
| Key points | Intranasal esketamine, administered over an average of 129 sessions (2.5 years), led to significant reductions in depression and anxiety scores, with 85% of patients improving in depressive severity and 25% achieving remission, while side effects were generally mild and transient. |
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.
Comparable studies
Other non-randomized and open-label trials on esketamine for depression, most cited first.