Among adult patients with major depressive disorder (MDD), no antidepressant effect was seen from single or repeated oral administration of ethosuximide, making it unlikely that this therapy can elicit ketamine-like, rapidly acting antidepressant effects in this patient population, according to a study published in European Archives of Psychiatry and Clinical Neuroscience.

A preclinical study suggested that the anticonvulsant ethosuximide may elicit ketamine-like, rapidly acting antidepressant effects. This randomized, double-blind, placebo-controlled trial enrolled participants from 3 mental health centers in China and was designed to evaluate the efficacy of ethosuximide compared with placebo in nonmedicated adult participants meeting the DSM-5 criteria for MDD. Participants were randomly assigned into permuted groups of 10, receiving ethosuximide (500, 1000, or 1500 mg) or placebo, which was administered only once or daily for 2 weeks. Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HAM-D) and the Montgomery–Åsberg Depression Rating Scale (MADRS); anxiety symptoms were assessed using the Hamilton Anxiety Rating Scale; and dependent symptoms were examined using the Visual Analog Scale (VAS).

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A total of 80 participants (20 per group) completed the study through the final assessment. No significant difference was seen in HAM-D score changes from baseline at 5 hours in participants given ethosuximide compared with those given placebo (P =.243), or at 2 weeks after repeated administration (P =.263). No significant difference was seen in MADRS scores from baseline at 5 hours between ethosuximide and placebo (P =.214), or from baseline to 2 weeks after repeated administration (P =.260). No significant differences between ethosuximide and placebo were seen in HAM-A scores at 5 hours (P =.425) or 2 weeks (P =.824), or in VAS scores at 5 hours (P =.474) or 2 weeks (P =.623). No serious adverse events were reported.

Study investigators conclude, “we could not find any antidepressant effect of ethosuximide on the clinician-reported HAM-D and MADRS scores after single and repeated oral administration. Therefore, it is unlikely that ethosuximide elicits ketamine-like rapid-acting antidepressant actions in patients with MDD, but the negative findings need to be replicated by other research groups.”


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Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Zhang K, Jia G, Xia L, et al. Efficacy of anticonvulsant ethosuximide for major depressive disorder: a randomized, placebo-control clinical trial [published online February 1, 2020]. Eur Arch Psychiatry Clin Neurosci. doi: 10.1007/s00406-020-01103-4