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Stanford research finds gene variations that alter antidepressant side effects

STANFORD, Calif. - Researchers at Stanford University Medical Center have identified a genetic marker that can explain why some people experience side effects to common antidepressants while others do not. They also found that a key liver enzyme involved in breaking down these antidepressants surprisingly played no role in the development of side effects nor in how well the drugs worked. The findings may lead to fewer side effects for patients undergoing antidepressant drug therapy.

"Antidepressants are among the most widely prescribed medications in the world," said lead author Greer Murphy Jr., MD, PhD, associate professor of psychiatry and behavioral sciences. "One of the mysteries at this point is why some people get debilitating side effects and others don't."

To start solving the mystery, Murphy and Alan Schatzberg, MD, the Kenneth T. Norris Jr. Professor of Psychiatry and Behavioral Sciences, wanted to find differences among patients in the function of proteins - and the genes that encode those proteins - that could account for the varied response to drug treatment. Their findings appear in the October issue of the American Journal of Psychiatry.

Good candidate proteins for studying an antidepressant response include the receptors that the drug interacts with in the brain and the enzymes in the liver that metabolize the drugs. Murphy and Schatzberg chose one of each for their research. In what Murphy said is the only double-blind randomized prospective psychiatric genetic study of its kind, the researchers analyzed DNA samples from 246 depressed patients who were randomly assigned either paroxetine (marketed as Paxil) or mirtazapine (marketed as Remeron) for eight weeks.

All of the patients studied in 18 U.S. outpatient clinics were 65 years of age or older. Side effects are particularly relevant in this age group, Murphy said. Older people, for example, are more susceptible to injury from a fall caused by dizziness
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Contact: Mitzi Baker
mitzibaker@stanford.edu
650-725-2106
Stanford University Medical Center
30-Sep-2003


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