Prospects for antidepressant drug discovery

Recent socioeconomic analyses found that depression is a leading cause of disability and a major risk factor for development of other diseases. Moreover, on a world-wide scale depression is underdiagnosed and undertreated. Current antidepressant drugs have proven to be effective, but are burdened with slow onset of action and side effects. Above this, it is still unclear by which pharmacological mode of action they exert their clinical effects. Hypothesis-driven research based upon the corticosteroid receptor hypothesis of depression has led to a novel concept focusing on brain neuropeptide receptors, specifically the corticotropin-releasing hormone (CRH) receptor as drug target. This treatise expands on this new development, its background and its promises including first clinical experiments. In the era of functional genomics, however, hypothesis-driven research will be complemented by a new strategy that relies on a 'bottom up' search for new drug targets through screening techniques that range from the use of DNA microarrays, searches of compound libraries to behavioral screens of mouse mutants, just to name a few. In this sense, biotechnology opens up new chances for drug development through serendipity by providing new data bases on which systematic biological research in psychiatry and psychology can be conducted. (C) 2001 Elsevier Science B.V. All rights reserved.