Gene helps predict whether antidepressant will work

CHICAGO Wed Aug 1, 2007 12:41am EDT

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CHICAGO (Reuters) - Scientists have found a second gene that helps predict whether people with depression will respond to a commonly prescribed antidepressant, U.S. researchers said on Tuesday.

On its own, the gene variation plays only a small role in predicting a patient's response to Forest Laboratories Inc.'s Celexa, known generically as citalopram.

But when a patient also had a variation of another gene, they were 23 percent more likely to benefit, according to the study which appears in the American Journal of Psychiatry.

The finding may one day give doctors a better shot at choosing the right antidepressant for the right patient, helping to eliminate the trial-and-error process many people undergo before they find an effective treatment.

"This is definitely a step ahead," said Dr. Gonzalo Laje, a researcher at the National Institute of Mental Health, in a telephone interview.

He said depression will be the second-leading cause of disability by the year 2020.

"It's huge. It costs the U.S. over $43 billion every year in terms of direct and indirect medical costs."

"If we can identify markers that would predict who gets better with which treatment, we can maybe decrease this burden and make the disease easier to treat," Laje said.

He said researchers will need to identify more markers before the research will be of use, but it helps scientists better understand the disease and gives a clearer picture of who might benefit.

Ideally, Laje would like to be able to find enough gene variants to predict when a patient is 95 percent more likely to benefit.

Celexa is in a class of drugs called SSRIs, or selective serotonin reuptake inhibitors.

Researchers studied DNA samples collected in the $35 million, seven-year Sequenced Treatment Alternatives to Relative Depression, or STAR*D, a study paid for by the National Institute of Mental Health.

Earlier findings from this study found Celexa sent 37 percent of patients who took it into remission.

In the latest study, researchers examined genetic material from 1,816 patients, comparing data from those who responded to Celexa and those who didn't.

They found people with a variation in the GRIK4 gene were more likely to respond to the drug, especially when they also had a variation of the HTR2A gene.

Prior studies have shown variations in the HTR2A gene -- which makes a protein related to the chemical messenger serotonin -- play a role in a patient's response to Celexa.

The GRIK4 gene makes a protein that is involved with the glutamate system, which also has been linked with depression.

Researchers said the findings are building a better picture of the biological mechanisms that underlie depression, a disease that affects about 121 million people worldwide, according to the World Health Organization.

In the United States, an estimated 21 million adults, or 9.5 percent of the population, have depression at some point. It is the leading cause of suicide.

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