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Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression

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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.

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Acknowledgements

The authors express their gratitude to the participants in this study and to the staff of PRODAF - Programa de Transtornos Afetivos, Federal University of Sao Paulo.

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Authors and Affiliations

  1. PRODAF-Programa de Transtornos Afetivos, Department of Psychiatry, Federal University of Sao Paulo, Rua Major Maragliano, 241, Vila Mariana, Sao Paulo, SP, 04017-030, Brazil

    Juliana Surjan, José Alberto Del Porto, Rodrigo Simonini Delfino, Raphael de Oliveira Cerqueira, Matheus Souza Steglich, Guilherme Lozi Abdo & Acioly Luiz Tavares Lacerda

  2. CNS Unit, BR Trials, Sao Paulo, Brazil

    Julia Diniz Grossi & Acioly Luiz Tavares Lacerda

  3. Centro Alfa de Humanização, Escola Paulista de Medicina, Federal University of Sao Paulo, Sao Paulo, Brazil

    Ana Cecília Lucchese, Eduardo Magalhães, Lorena Catarina Del Sant, Marco Aurélio Tuena, Carolina Nakahira, Victor Augusto Rodovalho Fava, Matheus Ghossain Barbosa & Luciana Maria Sarin

  4. LiNC-Laboratory of Integrative Neuroscience, Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil

    Acioly Luiz Tavares Lacerda

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  1. Juliana Surjan
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  2. Julia Diniz Grossi
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Corresponding author

Correspondence to Acioly Luiz Tavares Lacerda.

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Funding

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). The funding institutions played no role in the study design, data collection, statistical analysis, or data interpretation, in the manuscript writing, or in the decision to submit the article for publication.

Conflicts of interest

Acioly Luiz Tavares Lacerda has received consulting fees from Hoffmann-La Roche, Genentech, Janssen Pharmaceutical, Daiichi Sankyo, Cristalia Produtos Químicos e Farmacêuticos, Pfizer, Mantecorp Indústria Química e Farmacêutica, Libbs Farmacêutica, FQM Farma, and Sanofi-Aventis over the last 24 months and has received research fees from Janssen Pharmaceutical, Eli Lilly, H. Lundbeck A/S, Servier Laboratories, Hoffman-La Roche, FQM Farma, and Forum Pharmaceuticals. Juliana Surjan reports personal fees from Cristalia Produtos Químicos e Farmacêuticos and Abbot and non-financial support from Janssen Pharmaceutical, outside the submitted work. Carolina Nakahira reports non-financial support from Eurofarma, Sanofi-Aventis, and Cristalia Produtos Quimicos e Farmaceuticos, outside the submitted work. Raphael de Oliveira Cerqueira reports personal fees from Janssen Pharmaceutical and Abbot, outside the submitted work. Luciana Maria Sarin reports personal fees from Daiichi Sankyo Brasil, Lundbeck A/S, Pfizer, and Janssen Pharmaceutical, and non-financial support from Takeda Brasil, Moksha8 Brasil, and Torrent Pharma, outside the submitted work. Eduardo Magalhães reports non-financial support from Torrent Pharma and Hypera Pharma, outside the submitted work. José Alberto Del Porto reports being an active speaker and board advisor at Daiichi Sankyo Brasil, Pfizer, Janssen Pharmaceutical, Cristalia Produtos Quimicos e Farmaceuticos, Libbs Farmaceutica, H. Lundbeck A/S, Wyeth, Ache Laboratorios Farmaceuticos, and Eurofarma. The remaining authors declare no potential conflicts of interest.

Ethics approval

The study was approved by the local institutional review board (no. 3.115.329). All procedures in this study were in accordance with the 1964 Declaration of Helsinki.

Consent to participate

All participants signed the approved version of the written informed consent before performing any procedure related to the study. Patients were asked to attend all treatment sessions accompanied by a responsible adult. All interviews were conducted by trained psychiatrists. Data were inserted into a databank using the RedCap platform.

Consent for publication

Not applicable.

Availability of data and material

The datasets analyzed in the current study are not publicly available because of local policies.

Code availability

Not applicable.

Author contributions

ALTL designed the study, wrote the protocol, undertook statistical analyses, and revised the manuscript. JS wrote the manuscript, participated in the data collection, and interpreted the results. JDG helped write the manuscript and analyze the results. JADP helped design the study and implement the study’s research unit. LMS helped design the study, write the protocol, and implement the study’s research unit. RSD participated in the data collection and helped extract data from the bank. ROC helped write the manuscript. EM, LCDS, ACL, MAT, CN, VARF, MSS, and MGB participated in the data collection.

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Surjan, J., Grossi, J.D., Del Porto, J.A. et al. Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression. Clin Drug Investig 42, 865–873 (2022). https://doi.org/10.1007/s40261-022-01193-z

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