Anticonvulsant Ethosuximide Fails to Elicit Antidepressant Effect in MDD

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).

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.”

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