title: Novel targets for antidepressant therapies.
abstract: Most depressed patients fail to achieve remission despite adequate antidepressant monotherapy, and a substantial minority show minimal improvement despite optimal and aggressive therapy. However, major advances have taken place in elucidating the neurobiology of depression, and several novel targets for antidepressant therapy have emerged. Three primary approaches are currently being taken: 1) optimizing the pharmacologic modulation of monoaminergic neurotransmission, 2) developing medications that target neurotransmitter systems other than the monoamines, and 3) directly modulating neuronal activity via focal brain stimulation. We review novel therapeutic targets for developing improved antidepressant therapies, including triple monoamine reuptake inhibitors, atypical antipsychotic augmentation, dopamine receptor agonists, corticotropin-releasing factor-1 receptor antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, N-methyl-D-aspartate receptor antagonists, nemifitide, omega-3 fatty acids, and melatonin receptor agonists. Developments in therapeutic focal brain stimulation include vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, and deep brain stimulation.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 101 Woodruff Circle Northeast, Suite 4000, Atlanta, GA 30322, USA. pholtzh@emory.edu
authors.forename: Paul E
authors.initials: PE
authors.lastname: Holtzheimer
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D046690:Deep Brain Stimulation; D003865:Major Depressive Disorder / Q000503:physiopathology / Q000628:therapy*; D004359:Drug Therapy, Combination; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D004565:Electroconvulsive Therapy; D006801:Humans; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D050781:Transcranial Magnetic Stimulation; D055536:Vagus Nerve Stimulation
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D015306:Biogenic Monoamines; D015507:Drugs, Investigational; D017981:Receptors, Neurotransmitter