Novel targets for antidepressant therapies

• Authors: Paul Holtzheimer, Emory University; Charles B. Nemeroff, Emory University
• Journal Title: Current Psychiatry Reports
• Volume: Volume 10, Number 6
• Publisher: Springer (part of Springer Nature): Springer Open Choice Hybrid Journals | 2008-12-01, Pages 465-473
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s11920-008-0075-5
• Subjects: Health Sciences, Mental Health; Psychology, Clinical
• Keywords: Antidepressive Agents; Antipsychotic Agents; Biogenic Monoamines; Brain; Deep Brain Stimulation; Depressive Disorder, Major; Drug Therapy, Combination; Drugs, Investigational; Electroconvulsive Therapy; Humans; Receptors, Neurotransmitter; Transcranial Magnetic Stimulation; Vagus Nerve Stimulation

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.