2026 ECNP Congress

PS03-3198

Intranasal esketamine for treatment-resistant depression in older adults (>65 years): a prospective real-world study

Raquel Vidaurrazaga Jimenez — D. Vegas Renom, P. Molla, V. Soria, D.J. Palao, V. Gálvez · Parc Tauli Hospital Universitari, Mental Health department, Sabadell, Spain

2026 ECNP Congress

Introduction

Treatment-resistant major depressive disorder (TRD) in older adults is associated with chronicity, medical comorbidity, psychiatric comorbidity, and reduced response to conventional pharmacological strategies. Evidence supporting the use of intranasal esketamine (IN ESK) in patients aged 65 years or older remains limited and inconclusive, both in randomized controlled trials [1] and in real-world clinical settings [2], [3].

Aims

To evaluate longitudinal response and remission rates at 1, 3, 6 and 12 months in a cohort of 20 patients aged 65 years or older with TRD treated with intranasal esketamine in routine clinical practice.

Methods

This was a prospective, longitudinal, observational cohort study conducted in a real-world clinical setting. The initial cohort comprised 12 patients aged 65 years or older who met diagnostic criteria for TRD, either in unipolar major depressive disorder or bipolar depression. TRD was defined as failure to achieve an adequate clinical response to at least three prior antidepressant treatment strategies, including pharmacological combinations or augmentation approaches. Depressive symptom severity was assessed at each visit using the Montgomery–Asberg Depression Rating Scale (MADRS), administered by trained clinicians. Primary outcomes included response, defined as a reduction of 50% or more in MADRS total score from baseline, and remission, defined as a MADRS score of 10 or less. Outcomes were evaluated at 1, 3, 6, and 12 months. Sample size varied across time points due to treatment continuation and follow-up availability. Descriptive statistical methods were used to summarise demographic and clinical variables. Esketamine doses ranged between 56 mg and 112 mg, adjusted individually according to clinical response, tolerability, and clinician judgement.

Results

All patients completed induction phases exceeding 8 weeks and continued maintenance treatment beyond 6 months. The mean age was 69.5 years (range 65–75), and 67% of participants were female. Diagnoses included recurrent major depressive disorder in 58%, single-episode major depressive disorder in 34%, and bipolar II disorder in 8%. Psychiatric comorbidity was present in 17% of patients, and 17% had received prior electroconvulsive therapy during the current depressive episode. Response and remission rates increased over time: at 1 month, 66% and 25% (n=12); at 3 months, 83% and 66% (n=12); at 6 months, 100% and 90% (n=10); and at 12 months, 100% and 100% (n=6). No patients were lost to follow-up during the observation period. The mean administered dose was 72.8 mg (range 56–112 mg). Intranasal esketamine was generally well tolerated, and no treatment discontinuations occurred due to adverse effects.

Conclusions

In this geriatric cohort with highly resistant TRD, intranasal esketamine was associated with sustained and progressive clinical improvement, with high response and remission rates maintained over 12 months of follow-up. These findings differ from prior randomized controlled trial data in older adults and may be explained by individualized dosing strategies, including doses exceeding 84 mg, as well as longer induction and maintenance phases. However, results should be interpreted cautiously due to the small sample size, absence of a control group, and observational study design.

References

  1. Ochs-Ross, R., Daly, E. J., Zhang, Y., Lane, R., Lim, P., Morrison, R. L., Hough, D., Manji, H., Drevets, W. C., & Singh, J. B. (2020). Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression (TRANSFORM-3). JAMA Psychiatry, 77(2), 121–130.
  2. Wajs, E., Aluisio, L., Holder, R., Daly, E. J., Lane, R., Lim, P., George, J. E., Morrison, R. L., Sanacora, G., Young, A. H., Manji, H. K., & Singh, J. B. (2020). Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: Results of a long-term, open-label, phase 3 safety and efficacy study (SUSTAIN-2). Journal of Clinical Psychiatry, 81(3), 19m12891.
  3. De Bartolomeis, A., Martinotti, G., Di Giannantonio, M., et al. (2022). Real-world experience of esketamine use to manage treatment-resistant depression: A multicentric study on safety and effectiveness (REAL-ESK study). Journal of Affective Disorders, 319, 646–654.