Emerging targets for antidepressant therapies

Jeffrey J. Rakofsky, Paul E. Holtzheimer, Charles Nemeroff

Research output: Contribution to journalArticle

59 Citations (Scopus)

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).

Original languageEnglish
Pages (from-to)291-302
Number of pages12
JournalCurrent Opinion in Chemical Biology
Volume13
Issue number3
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

Fingerprint

Antidepressive Agents
Brain
Neurotransmitter Agents
Melatonin Receptors
Neurokinin-1 Receptors
Dopamine Agonists
Glucocorticoid Receptors
Omega-3 Fatty Acids
N-Methyl-D-Aspartate Receptors
Antipsychotic Agents
Therapeutics
Neurokinin-1 Receptor Antagonists
Modulation
Treatment-Resistant Depressive Disorder
Vagus Nerve Stimulation
Deep Brain Stimulation
Neurobiology
Transcranial Magnetic Stimulation
Networks (circuits)
Synaptic Transmission

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry

Cite this

Emerging targets for antidepressant therapies. / Rakofsky, Jeffrey J.; Holtzheimer, Paul E.; Nemeroff, Charles.

In: Current Opinion in Chemical Biology, Vol. 13, No. 3, 01.06.2009, p. 291-302.

Research output: Contribution to journalArticle

Rakofsky, Jeffrey J. ; Holtzheimer, Paul E. ; Nemeroff, Charles. / Emerging targets for antidepressant therapies. In: Current Opinion in Chemical Biology. 2009 ; Vol. 13, No. 3. pp. 291-302.
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