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Glutamatergic modulators are poorly understood, but promising therapies in depressive disorders

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Abstract

Treatment-resistant depression (TRD) affects many people with major depressive disorder or bipolar disorder. Glutamate is the key excitatory neurotransmitter in the CNS, and the confirmed rapid-acting antidepressant (RAAD) efficacy of the glutamatergic agent ketamine has fuelled extensive research into other glutamatergic agents. While mixed results have been reported in clinical trials, several glutamate receptor antagonists, including glycine site modulators, show promise as RAADs for severe TRD. The place of glutamatergic agents in the hierarchy of treatment for TRD is yet to be determined as more robust long-term efficacy and safety data are required. Nevertheless, ketamine and esketamine appear to be useful options for the rapid treatment of TRD.

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  1. Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Caroline Fenton & Arnold Lee

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  1. Caroline Fenton
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  2. Arnold Lee
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Correspondence to Arnold Lee.

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The preparation of this review was not supported by any external funding.

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C. Fenton, a contracted employee of Adis International Ltd/Springer Nature, and A. Lee, a salaried employee of Adis International Ltd/Springer Nature, declare no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Fenton, C., Lee, A. Glutamatergic modulators are poorly understood, but promising therapies in depressive disorders. Drugs Ther Perspect 38, 7–12 (2022). https://doi.org/10.1007/s40267-021-00882-7

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