There is insufficient evidence to determine if current gene-based tests intended to personalize selective serotonin reuptake inhibitor dose can improve patient outcomes or improve clinical decision-making, according to a new evidence report supported by two US government agencies, the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention.

The report found that tests evaluating differences in genes belonging to the Cytochrome P450, or CYP450, family that affect the rate at which a person metabolizes the drug are largely accurate. However, the researchers did not find any evidence that such tests led to improved patient outcomes or had an impact on treatment decisions for patients with depression. The researchers noted that other genetic factors and non-genetic factors such as diet and other medical conditions may have an impact on a patient’s response to treatment.

“This report highlights how systematically reviewing scientific findings can help guide future research,” said Beth A. Collins Sharp, Ph.D., R.N., director of AHRQ’s Evidence-based Practice Center Program. “This information will help identify the types of studies that are necessary to help better understand various treatment response issues.”

Researchers performed a comprehensive review of the literature and found no well-designed studies that evaluated clinical outcomes of tests to detect differences in genes belonging to the CYP450 family. These genes produce enzymes that degrade both the antidepressant class and many other drug types.
Most studies included a small number of people, did not test for all variations of the enzymes, and were poorly designed, according to the researchers. The majority of studies also reported the rate of metabolism after just one dose or were done in patients without depression?factors that do not accurately represent the long-term use of these drugs in patients with depression.

Because patient response varies, there has been strong interest in using gene-based tests to predict whether the person will be a poor, intermediate, extensive, or ultra-rapid metabolizer. Theoretically, ultra-rapid metabolizers could require higher doses than patients who metabolize the drug slowly. Poor metabolizers might respond to a lower dose, which could also prevent side effects. The goal of testing is to personalize health care by selecting therapy based on a patient’s genetic makeup.

The report found a relationship between genetic differences and the occurrence of adverse drug effects in depressed patients in two of six studies. However, the researchers concluded that all six studies were poorly designed, which limits the ability to draw conclusions about how differences in CYP450 genes influence adverse drug effects.

“This report emphasizes that well-designed observational studies and clinical trials are needed to clearly establish the clinical validity and utility of the many emerging genomic tests for treatment and prevention of common diseases of public health significance,” said Muin Khoury, M.D., Ph.D., director of CDC’s National Office of Public Health Genomics. “Early availability of the evidence base is key to the effective use of genomics for the benefit of population health.”

The report was prepared by a team of researchers led by David Matchar, M.D, and Mugdha Thakur, M.D., of the Duke University Evidence-based Practice Center in Durham, North Carolina.

Testing for CYP450 Polymorphisms in Adults With Non-Psychotic Depression Treated With SSRIs can be found online at http://www.ahrq.gov/clinic/tp/cyp450tp.htm.