Jul 27, 2009

Emerging targets for antidepressant therapies

PMID: 19501541

TITLE: Emerging targets for antidepressant therapies.

AUTHORS: Jeffrey J Rakofsky, Paul E Holtzheimer, Charles B Nemeroff

AFFILIATION: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 2004 Ridgewood Dr, Suite 218, Atlanta, GA 30322, United States.

REFERENCE: Curr Opin Chem Biol 2009 Jun 13(3):291-302

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 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 CRF(1) 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).