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 via PubMed
Summary
AI-generated from the abstractMood disorders are long-lasting conditions with inconsistent remission rates. Standard antidepressants fail many patients, cause side effects like weight gain and sexual problems, and act slowly. Newer drugs aim to work faster, with fewer side effects, and target symptoms poorly addressed by older medications, such as anhedonia, suicidal thoughts, insomnia, cognitive deficits, and irritability. These agents act on glutamate, GABA, orexin, and other receptors, offering more pharmacodynamic variety to personalize treatment. This review covers the clinical profiles of nine novel compounds—including psilocybin, esmethadone, and zuranolone—to help clinicians weigh benefits and risks for patients with different mood disorder symptoms and comorbidities.
Study at a glance
| 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 Neuroscience Psychiatric medicine Drug development |
| Citations | 40 |
| Key finding | 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.