Emerging targets for antidepressant therapies

• Type of Material: Article
• Authors: Jeffrey Rakofsky, Emory University; Paul Holtzheimer, Emory University; Charles B Nemeroff, Emory University
• Language: English
• Date: 2009-06-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cbpa.2009.04.617
• Title of Journal or Parent Work: Current Opinion in Chemical Biology
• ISSN: 1367-5931
• Volume: 13
• Issue: 3
• Start Page: 291
• End Page: 302
• Grant/Funding Information: The authors were supported by the NIH/National Institute of Mental Health (MH 58922, MH 42088, MH 69056, and MH 77083; MH 77869); and NARSAD.; PEH is supported by grants from the Dana Foundation; NARSAD; National Institute of Mental Health (K23 MH-077869); National Institutes of Health Loan Repayment Program; Stanley Medical Research Institute; and Woodruff Foundation.
• Keywords: OBSESSIVE-COMPULSIVE DISORDER; DEEP BRAIN-STIMULATION; Science & Technology; Biochemistry & Molecular Biology; SEROTONIN REUPTAKE INHIBITORS; VAGUS-NERVE-STIMULATION; MAJOR DEPRESSIVE DISORDER; Life Sciences & Biomedicine; TREATMENT-RESISTANT DEPRESSION; CORTICOTROPIN-RELEASING-FACTOR; GENERALIZED ANXIETY DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; Biophysics; PLACEBO-CONTROLLED TRIAL
• Research Categories: Health Sciences, Mental Health; Psychology, Clinical

Abstract

Despite adequate antidepressant monotherapy, the majority of depressed patients do not achieve remission. Even optimal and aggressive therapy leads to a substantial number of patients who show minimal and often only transient improvement. In order to address this substantial problem of treatment-resistant depression, a number of novel targets for antidepressant therapy have emerged as a consequence of major advances in the neurobiology of depression. Three major approaches to uncover novel therapeutic interventions are: first, optimizing the modulation of monoaminergic neurotransmission; second, developing medications that act upon neurotransmitter systems other than monoaminergic circuits; and third, using focal brain stimulation to directly modulate neuronal activity. We review the most recent data on novel therapeutic compounds and their antidepressant potential. These include triple monoamine reuptake inhibitors, atypical antipsychotic augmentation, and dopamine receptor agonists. Compounds affecting extra-monoamine neurotransmitter systems include CRF1 receptor antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, NMDA receptor antagonists, nemifitide, omega-3 fatty acids, and melatonin receptor agonists. Focal brain stimulation therapies include vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS).