title: Issues encountered in recent attempts to develop novel antidepressant agents.
abstract: The development of new antidepressants has had mixed results over the past decade, with several notable failures. This paper reviews a number of major initiatives in the development of new antidepressant agents. Traditional strategies to build on agents that have monoaminergic effects at the synapse (e.g., vilazodone and ketamine) have been complemented with efforts that have emphasized devices and brain circuits (e.g., deep brain stimulation and transcranial magnetic stimulation) or chemical agents that modulate neuroendocrine systems (e.g., glucocorticoid antagonists, mixed melatonin agonists/serotonin type-2 receptor antagonists). Interestingly, chemical agents, such as onabotulinumtoxin A, may affect brain circuits as well. We present data from recent studies in drug and device development--reviewing progress made, stumbling blocks encountered, and issues that need to be addressed in future studies.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
mesh_terms: D000928:Antidepressive Agents / Q000302:isolation & purification* / Q000627:therapeutic use; D001572:Benzofurans / Q000627:therapeutic use; D046690:Deep Brain Stimulation; D003866:Depressive Disorder / Q000188:drug therapy; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007649:Ketamine / Q000627:therapeutic use; D009415:Nerve Net / Q000502:physiology; D009490:Neurosecretory Systems / Q000502:physiology; D010879:Piperazines / Q000627:therapeutic use; D015990:Placebo Effect; D013440:Sulfides / Q000627:therapeutic use; D050781:Transcranial Magnetic Stimulation; D000069503:Vilazodone Hydrochloride; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D001572:Benzofurans; D007211:Indoles; D010879:Piperazines; D013440:Sulfides; D000078784:Vortioxetine; D007649:Ketamine; D000069503:Vilazodone Hydrochloride
keywords: antidepressants; glutamate; ketamine; major depression; onabotulinumtoxin