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Clinical specificity profile for novel rapid acting antidepressant drugs.

Mauro Scala, Giuseppe Fanelli, Diana De Ronchi, Alessandro Serretti, Chiara Fabbri

International Clinical Psychopharmacology September 1, 2023 DOI: 10.1097/yic.0000000000000488 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Population Patients with mood disorders
Interventions 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) zuranolone (SAGE-217)
Keywords Antidepressants Mental health treatment Psychiatric medicine Drug development
Citations 40
Key findings Novel antidepressants targeting glutamate, GABA, and orexin receptors may provide faster action, better tolerability, and effectiveness for specific symptoms like anhedonia and suicidal ideation, potentially allowing more personalized treatment for mood disorders.

Abstract

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.