title: Investigational drugs in recent clinical trials for treatment-resistant depression.
abstract: The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and USA and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week. This observation was a turning point that opened the way for other, more selective glutamatergic modulators (intranasal esketamine, AVP-786, AVP-923, AV-101, and rapastinel). Of the remaining compounds, monoclonal antibodies open highly innovative therapeutic options, based on new pathophysiological approaches to depression. Expert commentary: Promising new agents are emerging for TRD treatment. Glutamatergic modulators likely represent a very promising alternative to monoaminergic antidepressant monotherapy. We could see the arrival of the first robust and rapid acting antidepressant drug in the near future, which would strongly facilitate the ultimate goal of recovery in persons with TRD.
authors.affiliation: a Pharmacology and Therapeutics, Craven , Villemoisson-sur-Orge , France.
authors.forename: Ricardo P
authors.initials: RP
authors.lastname: Garay
authors.affiliation: b Experimental Therapeutics and Pathophysiology Branch , National Institute of Mental Health, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.affiliation: c Centre Médico-Psychologique B, CHU , Université d'Auvergne , Clermont-Ferrand , France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Charpeaud
authors.affiliation: d Department of Psychiatry and Behavioral Sciences , New York Medical College , Valhalla , NY , USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.affiliation: e Psychiatry Research, Northwell Health , The Zucker Hillside Hospital , Glen Oaks , New York , USA.|f Hofstra Northwell Health School of Medicine , Hempstead , New York , USA.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.affiliation: a Pharmacology and Therapeutics, Craven , Villemoisson-sur-Orge , France.
authors.forename: Ahcène
authors.initials: A
authors.lastname: Hameg
authors.affiliation: c Centre Médico-Psychologique B, CHU , Université d'Auvergne , Clermont-Ferrand , France.
authors.forename: Pierre-Michel
authors.initials: PM
authors.lastname: Llorca
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003863:Depression / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D003915:Dextromethorphan; D004338:Drug Combinations; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006801:Humans; D011802:Quinidine
chemical_list: D000928:Antidepressive Agents; D004338:Drug Combinations; D015507:Drugs, Investigational; C507057:dextromethorphan - quinidine combination; D003915:Dextromethorphan; D011802:Quinidine
keywords: AV-101; AVP-786; brexpiprazole; buprenorphine; cariprazine; clinical trials; esketamine; ketamine; rapastinel; treatment-resistant depression