Treating Bipolar Depression with Esketamine: Safety and Effectiveness data from a naturalistic multicentric study on Esketamine in Bipolar versus Unipolar Treatment-Resistant Depression
This open-label study (n=70) compared the effect of esketamine (28-84mg; 8x) in those with bipolar treatment-resistant depression (B-TRD, n=35) and those with unipolar TRD. There was no significant difference between the two groups on depression scores, and both responded to treatment. Those in the B-TRD group had more anxiety-reducing effects. This study is part of the REAL-ESK study.
Authors
- Roger McIntyre
Published
Abstract
Background
Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD.
Objectives
To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch.
Methods
Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up.
Results
A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch.
Conclusions
Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.
Research Summary of 'Treating Bipolar Depression with Esketamine: Safety and Effectiveness data from a naturalistic multicentric study on Esketamine in Bipolar versus Unipolar Treatment-Resistant Depression'
Introduction
Bipolar depression accounts for the majority of symptomatic time in both type I and type II bipolar disorder and is associated with high morbidity, suicidality, and limited effective treatment options. Conventional antidepressants have delayed onset, frequent poor tolerability, and risk provoking affective switches or rapid cycling in bipolar disorder. Brain stimulation techniques (ECT, rTMS, tDCS) offer alternatives for some patients, but a substantial proportion of people with bipolar depression remain partially responsive or treatment-resistant (B-TRD). Interest has therefore grown in glutamatergic agents such as ketamine and its S-enantiomer, esketamine, which have rapid antidepressant effects in unipolar TRD and a more favourable outpatient safety profile than intravenous ketamine; however, randomised data on esketamine in bipolar depression are lacking and regulatory guidance is cautious because of concerns about affective switching. This study aimed to provide preliminary real-world evidence on the antidepressant effectiveness, safety, and tolerability of esketamine nasal spray (ESK-NS) in patients with treatment-resistant bipolar depression, comparing outcomes with an age-matched sample of unipolar TRD. Secondary objectives included assessment of anxiolytic effects and the average risk of treatment-emergent affective switch in bipolar patients treated with ESK-NS. The investigation used retrospective multicentre data collected as part of an early access programme in Italy to address the current evidence gap regarding ESK-NS use in B-TRD.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Author
- APA Citation
Martinotti, G., Dell'Osso, B., Di Lorenzo, G., Maina, G., Bertolino, A., Clerici, M., Barlati, S., Rosso, G., Di Nicola, M., Marcatili, M., d'Andrea, G., Cavallotto, C., Chiappini, S., De Filippis, S., Nicolò, G., De Fazio, P., Andriola, I., Zanardi, R., Nucifora, D., . . . Vita, A. (2023). Treating Bipolar Depression with Esketamine: Safety and Effectiveness data from a naturalistic multicentric study on Esketamine in Bipolar versus Unipolar Treatment-Resistant Depression. Bipolar Disorders, 25(3), 233-244. https://doi.org/10.1111/bdi.13296
References (3)
Papers cited by this study that are also in Blossom
Zheng, W., Zhou, Y-L., Liu, W. et al. · Journal of Psychiatric Research (2018)
Mcintyre, R. S., Rosenblat, J. D., Nemeroff, C. B. et al. · American Journal of Psychiatry (2021)
Wei, C., Wang, J., An, D. et al. · Frontiers in Psychology (2021)
Cited By (4)
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Mallevays, M., Fuet, L., Danon, M. et al. · MedRvix (2026)
D'Andrea, G., Pettorruso, M., Di Lorenzo, G. et al. · Journal of Affective Disorders (2023)
Estrade, I., Petit, A. C., Sylvestre, V. et al. · Journal of Affective Disorders (2023)
Pepe, M., Bartolucci, G., Marcelli, I. et al. · Brain Sciences (2023)
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