Clinical specificity profile for novel rapid acting antidepressant drugs

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile. These new drugs were developed with the aim of combining a rapid action, a tolerable profile, and higher effectiveness on specific symptoms, which were relatively poorly targeted by standard antidepressants, such as anhedonia and response to reward, suicidal ideation/behaviours, insomnia, cognitive deficits, and irritability. This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs.

Automated summary

Mood disorders are chronic diseases with low remission rates and treatment options have limitations. New antidepressants targeting different receptors have been developed to provide rapid action, tolerability, and effectiveness on specific symptoms. This review discusses the clinical profile and efficacy/tolerability of new antidepressants, such as AV-101, dextromethorphan-bupropion, PH-10, pimavanserin, PRAX-114, psilocybin, REL-1017/dextromethadone, JNJ-42847922/MIN-202, and SAGE-217, in patients with mood disorders, aiming to help clinicians optimize the risk/benefit ratio when prescribing these drugs.