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Efficacy of anticonvulsant ethosuximide for major depressive disorder: a randomized, placebo-control clinical trial

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Abstract

Results of a preclinical study suggested that the anticonvulsant drug ethosuximide may elicit ketamine-like rapid-acting antidepressant actions. We evaluated the antidepressant efficacy of ethosuximide versus placebo in non-medicated adult patients with major depressive disorder (MDD). This randomized, double-blind, placebo-controlled trial included patients at three mental health centers in China. Eighty eligible adults (aged 18–65 years) met the DSM-5 criteria for MDD. Patients in the acute single study received three doses (500, 1000, or 1500 mg) of ethosuximide or placebo. Patients in the repeated study received ethosuximide (1500 mg/day) or placebo for 2 weeks. The Hamilton Depression Rating Scale (HAM-D), the Montgomery–Åsberg Depression Rating Scale (MADRS), and the Hamilton Anxiety Rating Scale were used to assess antidepressant and antianxiety responses to ethosuximide. No significant reductions in depression and anxiety rating scale scores were observed after a single oral administration of ethosuximide, in comparison with placebo. Furthermore, patients receiving ethosuximide for 2 weeks did not show reductions in depression and anxiety rating scale scores. There were no serious adverse events. Responses to the study’s primary and secondary outcome measures, the clinician-rated HAM-D and MADRS, showed no change from baseline to the end of treatment, with either ethosuximide or placebo. These results suggest that ethosuximide does not produce ketamine-like robust antidepressant actions in adult patients with MDD.

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Acknowledgements

We thank all the patients who volunteered to participate in the study. This study was supported by the National Nature Science Foundation of China (81801341), the Medical and Public Health Technology Research Projects of Wuxi Technology Bureau (CSE31N1723), the Wuxi Municipal Health and Family Planning Commission research project (MS201704), and AMED, Japan (to K.H., JP19dm0107119).

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Authors and Affiliations

  1. Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, Anhui, China

    Kai Zhang, Lei Xia & Huanzhong Liu

  2. Anhui Mental Health Center, Anhui Medical University, Hefei, Anhui, China

    Gang Jia & Rui Tao

  3. Department of Clinical Psychology, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangsu, China

    Jianbin Du, Guanchen Gai, Zhiqiang Wang, Leiming Cao, Fuquan Zhang & Guoqiang Wang

  4. Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan

    Kenji Hashimoto

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  1. Kai Zhang
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Correspondence to Kai Zhang.

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Dr. Hashimoto is an inventor on a filed patent application on “Application of R-ketamine and salt thereof as pharmaceuticals” by Chiba University. Dr. Hashimoto has received research support from Otsuka, Sumitomo-Dainippon, and Taisho. The other authors report no financial relationships with commercial interests.

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Zhang, K., Jia, G., Xia, L. et al. Efficacy of anticonvulsant ethosuximide for major depressive disorder: a randomized, placebo-control clinical trial. Eur Arch Psychiatry Clin Neurosci 271, 487–493 (2021). https://doi.org/10.1007/s00406-020-01103-4

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  • DOI: https://doi.org/10.1007/s00406-020-01103-4

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