TY - JOUR
T1 - Emerging targets for antidepressant therapies
AU - Rakofsky, Jeffrey J.
AU - Holtzheimer, Paul E.
AU - Nemeroff, Charles B.
N1 - Funding Information:
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. He is currently a consultant to Advanced Neuromodulation Systems (a division of St. Jude Medical), and has previously consulted to Tetragenex, Inc. and AstraZeneca, Inc. JJR has no financial relationships or other potential conflicts of interest to disclose.
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.
PY - 2009/6
Y1 - 2009/6
N2 - 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).
AB - 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).
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U2 - 10.1016/j.cbpa.2009.04.617
DO - 10.1016/j.cbpa.2009.04.617
M3 - Review article
C2 - 19501541
AN - SCOPUS:67649844041
VL - 13
SP - 291
EP - 302
JO - Current Opinion in Chemical Biology
JF - Current Opinion in Chemical Biology
SN - 1367-5931
IS - 3
ER -