Rapid-acting antidepressants.
Advances in pharmacology (San Diego, Calif.) January 1, 2019 Jeffrey M. Witkin, Anna E Martin, Lalit K Golani et al. 71 citations
A new class of antidepressants, emerging since 2006, offers rapid onset, large effect size, and efficacy after single or few doses, even in treatment-refractory patients and against symptoms like anhedonia. Controlled clinical studies have demonstrated rapid-acting effects for ketamine, other NMDA receptor antagonists, and scopolamine, with less clinical data for psychedelic drugs such as psilocybin, LSD, and ayahuasca. The mechanisms are not fully understood, but potentiation of AMPA receptor function appears to be a general trigger. Durability is limited for ketamine and scopolamine, while psychedelics may produce effects lasting months. Side effects and lack of enduring effects are primary impediments. Esketamine is FDA-approved; compounds in clinical development include (R)-ketamine, Rapastinel, and TAK-653. Preclinical evidence suggests potential for mGlu2/3 receptor antagonists, AMPA receptor potentiators, and GABAA(α5) negative allosteric modulators.