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Overview: Towards individualized treatment in schizophrenia
Author(s) -
Müller Daniel J.,
De Luca Vincenzo,
Kennedy James L.
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10287
Subject(s) - schizophrenia (object oriented programming) , pharmacogenetics , antipsychotic , clozapine , psychology , medicine , psychosis , psychiatry , bioinformatics , clinical psychology , gene , genetics , biology , genotype
Schizophrenia is a serious mental disorder involving distortions of thinking or perception, inappropriate or blunted affect, and cognitive deficits may evolve in the course of time. Antipsychotics are the first choice for treatment; however, interindividual variability in response and side effects are commonly observed. To avoid time‐consuming, cost‐intensive, and potentially hazardous drug treatments, clinicians should ideally anticipate which antipsychotic is the most effective and less harmful for a given patient. This form of “individualised treatment” can only succeed if specific characteristics are identified as highly associated with the favourable response. Demographical, clinical, or physiological characteristics by themselves have not been shown to predict antipsychotic drug response to a clinically meaningful extent. As genetic factors are likely to contribute substantially to the efficacy and toxicity of drugs, numerous pharmacogenetic studies have searched for associations between gene variants and antipsychotic drug response. The first generation of pharmacogenetic studies yielded mainly negative and often inconsistent findings that are most likely the result of substantial heterogeneity among studies generally using small samples. Perhaps the most robust associations were found between polymorphisms of the serotonin 2A or the dopamine 2 receptor genes with response to clozapine or conventional antipsychotics, respectively. However, effect sizes are rather small and, therefore, further research is needed that integrates recent advances in genomics, proteomics, and biostatistics. Nonetheless, these findings are consistent with the dopamine/serotonin hypothesis in schizophrenia. The continuous discovery of new gene variants and progressive methodological improvements will help elucidate the molecular pathological mechanisms in schizophrenia, and reveal new avenues for drug development research. Drug Dev. Res. 60:75–94, 2003. © 2003 Wiley‐Liss, Inc.