Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression
This open-label study (n=70) on suicidal ideation (SI) in patients with major depressive disorder (MDD) and bipolar depression (BD) finds that esketamine (1x p/w 6ws) led to significant reductions in SI at the end of the study (24h after last administration). There was no statistically significant difference between the two subpopulations.
Authors
- Acioly Luiz Tavares Lacerda
Published
Abstract
Background and Objective Affective disorders account for most cases of suicide. The pharmacological arsenal to treat suicidality is limited and available agents take too long to take effect. A large body of evidence shows optimal results of ketamine for treating depression, but the evidence concerning suicidality has not been fully described. We report the first real-world study of severely depressed patients presenting with suicide ideation who were treated with repeated administration of subcutaneous esketamine.
Methods
We analyzed data from 70 acutely depressed subjects diagnosed with resistant major depressive disorder or bipolar depression. Subjects were administered subcutaneous esketamine once a week for 6 weeks. The primary efficacy endpoint, the change from baseline to 24-h post-administration 6 in the item 10 Montgomery-Åsberg Depression Rating Scale score, was analyzed using a mixed-effects repeated-measures model.
Results
There were significant effects for time on item 10 Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001) but not for a time × diagnosis interaction (p = 0.164) from baseline to the end of the study. Efficacy of esketamine did not differ between groups (major depressive disorder vs bipolar depression) at any timepoint. Statistical significance on suicidality scores was observed from 24 h after the first administration (p < 0.001), and a further reduction was observed with repeated administrations. Esketamine was safe and well tolerated. Mean heart rate remained stable during the administrations and the blood pressure increase was self-limited.
Conclusions
Repeated subcutaneous esketamine administration had significant anti-suicidality effects in both major depressive disorder and bipolar groups, with a rapid onset of action and a good tolerability profile. Large randomized controlled trials are warranted to confirm these preliminary findings.
Research Summary of 'Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression'
Introduction
Suicide remains a major and rising public‑health problem, particularly among young people, and is closely associated with mood disorders such as major depressive disorder (MDD) and bipolar disorder. Existing anti‑suicidal interventions (for example lithium, clozapine, electroconvulsive therapy and psychotherapy) can be effective but typically take time to act or have important logistical and safety constraints. Earlier clinical and meta‑analytic research has identified rapid antidepressant and anti‑suicidal effects of ketamine and its S‑enantiomer esketamine, usually studied via intravenous or intranasal routes, but evidence specifically targeting suicidality as a primary outcome is limited and prior trials have often excluded patients at high suicide risk or used small samples. Surjan and colleagues aimed to examine whether repeated subcutaneous administrations of esketamine reduce suicidal ideation in treatment‑resistant major depressive episodes occurring in MDD or bipolar disorder. The study set out to evaluate efficacy using the item 10 score of the Montgomery‑Åsberg Depression Rating Scale (MADRS) as the primary endpoint, and to report safety and tolerability outcomes with a weekly six‑week dosing schedule delivered in a real‑world clinic setting. This investigation is presented as the first real‑world study to assess subcutaneous esketamine for suicidality in severely depressed patients.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Author
- APA Citation
Surjan, J., Grossi, J. D., Del Porto, J. A., Delfino, R. S., de Oliveira Cerqueira, R., Lucchese, A. C., Magalhães, E., Del Sant, L. C., Tuena, M. A., Nakahira, C., Fava, V. A. R., Steglich, M. S., Abdo, G. L., Barbosa, M. G., Sarin, L. M., & Lacerda, A. L. T. (2022). Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression. Clinical Drug Investigation, 42(10), 865-873. https://doi.org/10.1007/s40261-022-01193-z
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Papers in Blossom that reference this study
Estrade, I., Petit, A. C., Sylvestre, V. et al. · Journal of Affective Disorders (2023)
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