Neuropsychopharmacology (2008) 33, 2061–2079; doi:10.1038/sj.npp.1301639; published online 28 November 2007

The Evolution of Drug Development in Schizophrenia: Past Issues and Future Opportunities

William T Carpenter1 and James I Koenig1

1Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA

Correspondence: Dr WT Carpenter Jr, Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228, USA. Tel: +1 410 402 7101; Fax: +1 410 788 3837; E-mail: wcarpent@mprc.umaryland.edu

Received 16 May 2007; Revised 29 October 2007; Accepted 29 October 2007; Published online 28 November 2007.

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Abstract

Schizophrenia is a disease syndrome with major public health implications. The primary advance in pharmacotherapeutics was in 1952 with the introduction of antipsychotic medications (ie, chlorpromazine, dopamine D2 antagonism). Barriers to progress have been substantial, but many will be subject to rapid change based on current knowledge. There are attractive psychopathology indications for drug discovery (eg, impaired cognition and negative symptoms), and drugs with efficacy in these domains may have application across a number of disease classes. These pathologies are observed prior to psychosis raising the possibility of very early intervention and secondary prevention. Success in drug discovery for cognition and negative symptom pathologies may bring forth issues in ethics as the potential for enhancing normal function is explored.

Keywords:

antipsychotic drug, animal model, endophenotype cognition, negative symptoms, drug discovery

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