Rapid-Acting Antidepressants
Current Pharmaceutical Design October 19, 2018 Jeffrey M. Witkin, Daniel E. Knutson, Gabriel J. Rodriguez et al. 44 citations
Conventional antidepressants for major depression, which work by increasing monoamine neurotransmitters, can take weeks to produce a full response, a major limitation. This review describes compounds that provide immediate symptom relief, including ketamine, scopolamine, and newer agents like mGlu2/3 receptor antagonists, negative allosteric modulators of α5-containing GABAA receptors, and psychedelics. These rapid-acting drugs show large effect sizes and efficacy in treatment-resistant patients, though some have challenges with duration of effect and side effects. The proposed mechanism involves amplifying excitatory neurotransmission via AMPA receptors, triggered by increased glutamate efflux. Two compounds, GLYX-13 (Rapastinel) and esketamine, are in late-stage clinical development.