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Genetic variation can cloud schizophrenia Tx: African american patients. (treatment).

PHILADELPHIA -- Classic neuroleptic drugs are often metabolized more slowly in African Americans than in whites, leading to an increased risk of adverse effects from these drugs in African American patients.

Overdosing with classic neuroleptics such as haloperidol (Haldol) is just one facet of a pattern of substandard treatment for schizophrenia that African Americans receive, said L. DiAnne Bradford, Ph.D., at the annual meeting of the National Medical Association.

Schizophrenia is way overdiagnosed in African Americans, said Dr. Bradford, director of the Minority Mental Health Research Program at the Morehouse School of Medicine, Atlanta. About 30%-50% of African Americans with a clinical diagnosis of schizophrenia don't have schizophrenia; they have something else.

In addition, African Americans, in general, are prescribed higher doses of antipsychotic medications than are patients from other racial or ethnic groups, and they are treated with these drugs for longer periods of time.

Plus, African Americans who receive antipsychotic medications tend to have classic neuroleptics prescribed rather than the newer and more expensive atypical agents.

The last point is particularly important because of the relatively high prevalence of the slow- or intermediate-metabolizing phenotype among African Americans, Dr. Bradford said. This leads to high plasma levels of these drugs, which can cause extrapyramidal side effects, including movement disorders and tardive dyskinesia.

Many antipsychotic drugs, including classic neuroleptics such as haloperidol, are metabolized by the liver cytochrome P450 enzyme CYP2D6. More than 40 genetic alleles have been identified for this enzyme based on the functional activity of the protein that they code for. Many alleles code for forms of the CYP2D6 protein that have normal levels of enzymatic function, but some alleles code for forms of the protein that are either partially functional or completely nonfunctional. Depending on which alleles a person inherits, their phenotype can range from normal metabolizers to intermediate or slow metabolizers. The prevalence of the alleles that code for poorly functioning proteins varies among various racial and ethnic groups in the United States.

Among U.S. whites, the phenotype of intermediate or slow metabolizers occurs in about 5%-10% of the population. In contrast, among African Americans, it occurs in about 40% of the population. And among Asian Americans, it occurs in about 35% of the population, said Dr. Bradford.

Research is still in progress on how to apply this new genetic information to the management of schizophrenia, she added. The best way to identify patients who are slow or intermediate metabolizers of antipsychotic drugs is to perform a genetic analysis of the CYP2D6 alleles, which would cost about $300 per patients. However, the test is not yet routinely available to many physicians, and the specific alleles that primarily code for partially functional enzymes among African Americans have not been identified. Among Asian Americans, the most common allele with poor enzymatic function appears to the CYP2D[6.sup.*]10.

In addition, no standards have been yet been developed on how to adjust the dosages of antipsychotic medications for patients who carry alleles that make them poor metabolizers of these drugs, Dr. Bradford told this newspaper. For the time being, the best advice when treating African Americans with a classic neuroleptic is to start with a low dosage and then increase it slowly while watching for the development of adverse erects, she said.
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Title Annotation:Adult Psychiatry
Author:Zoler, Mitchel L.
Publication:Clinical Psychiatry News
Date:Sep 1, 2003
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