Novel targets for antidepressant therapies

• Type of Material: Article
• Authors: Paul Holtzheimer, Emory University; Charles B. Nemeroff, Emory University
• Language: English
• Date: 2008-12-01
• Publisher: Springer (part of Springer Nature): Springer Open Choice Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Current Medicine Group LLC 2008.
• Final Published Version (URL): http://dx.doi.org/10.1007/s11920-008-0075-5
• Title of Journal or Parent Work: Current Psychiatry Reports
• ISSN: 1523-3812
• Volume: 10
• Issue: 6
• Start Page: 465
• End Page: 473
• Grant/Funding Information: This work was supported by National Institutes of Health/National Institute of Mental Health grants MH-58922, MH-42088, MH-69056 and MH-77083 (to Dr. Nemeroff); and MH-77869 (to Dr. Holtzheimer); the National Institutes of Health Loan Repayment Program (Dr. Holtzheimer); and NARSAD (Dr. Holtzheimer).
• Keywords: Vagus Nerve Stimulation; Brain; Antidepressive Agents; Drug Therapy, Combination; Antipsychotic Agents; Electroconvulsive Therapy; Transcranial Magnetic Stimulation; Drugs, Investigational; Humans; Receptors, Neurotransmitter; Depressive Disorder, Major; Deep Brain Stimulation; Biogenic Monoamines
• Research Categories: Psychology, Clinical; Health Sciences, Mental Health

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.