Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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Augmentation Strategies to Improve Treatment of Major Depression

Author(s): Minke E. Jongsma, M.C.G. v. d. Hart, Joanna I. U. d. Haes, Thomas I.F.H. Cremers, Ben H.C. Westerink, Johan A. den Boer, Fokko J. Bosker.

Abstract:

The monoamine hypothesis has dominated almost forty years the psychopathology of depression. Yet this has not lead to antidepressants that are significantly more efficacious than the early tri- and tetracyclics from which they have evolved. Alternative hypotheses such as those involving adult neurogenesis or components of the hypothalamic-pituitaryadrenal- axis are either too premature or have not lead to drugs with improved antidepressant activity. Antidepressants may not be perfect, both in terms of efficacy and side effects, however their performance may be improved by making use of so-called augmentation strategies. Augmentation strategies that have potential to hasten and/or improve the therapeutic effect of antidepressants, in particular serotonin reuptake inhibitors, can have different forms. They can be aimed at reducing comorbid symptoms, such as anxiety, or they may be directed to processes that counteract the effect of serotonin reuptake inhibitors. Examples of the latter are those involving 5-HT1A and 5-HT1B autoreceptors, 5-HT 2C receptors and the availability of tryptophan. Another option could be exploring neuropeptide/serotonin interactions. The various augmentation strategies are reviewed in the context of literature data regarding neurobiology and pharmacotherapy of major depression.

Keywords: Antidepressant, augmentation, depressive symptoms, 5-HT receptors, neuroimaging, neuropeptides

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Article Details

VOLUME: 6
ISSUE: 2
Year: 2006
Page: [135 - 152]
Pages: 18
DOI: 10.2174/187152406777441899
Price: $58