Suicide-Gene Test Could Spawn Customized Drugs

Sept. 30 -- After years of unfulfilled promises, genomics finally seems poised to impact health care. Research from the National Institute of Mental Health has associated two genetic markers with suicidal thoughts in patients who take the antidepressant drug Celexa.

And an enterprising company called NeuroMark is piggybacking on the discovery, already offering a test for those gene markers.

"We think this test represents the leading edge of personalized medicine," said Kim Bechthold, CEO of NeuroMark, which produced the Mark-C test. "And (it's) a first in neuropsychiatry."

Genetic testing has been done for years, but most research has focused on rare diseases like cancer or Huntington's disease, so the impact on public health has been limited. And the Human Genome Project, launched more than a decade ago and completed in 2003, promised to revolutionize health care but has led to few breakthroughs so far.

The latest genetic tests, however, could put a dent in the large number of serious health problems and deaths caused by adverse drug reactions in the United States. Problems such as a disability or life-threatening hospitalization caused by prescription drugs more than doubled between 1998 and 2005 to 468,000, as did the number of deaths, to nearly 90,000.

In September, the FDA approved the first personlized genetic test for people who take a specific drug. The test, developed by Nanosphere, helps identify patients who might be at risk for complications when taking a frequently prescribed blood-thinning drug called warfarin.

Celexa has been prescribed to 8 million people in the United States and 30 million worldwide, according to the drug's manufacturer Forest Labs.

NeuroMark's test, which doesn't require FDA approval but has passed the Clinical Laboratory Improvement Amendments regulatory standards, will be available Monday for $500. The NeuroMark test includes the two suicidal-ideation genes identified in the new trial, plus two more that NIMH researchers will discuss in an upcoming paper, Bechtold said.

The test, however, is not yet covered by insurance, which has limited the use of previous tests.

The study appears in the October issue of the American Journal of Psychiatry. Scientists screened genetic material from 1,915 adult patients with major depression who were being treated with citalopram, Celexa's generic name. Variants of two genes, GRIK2 and GRIA3, increased the odds that patients would think about suicide. Both genes regulate how the brain processes glutamate, an amino acid that helps mediate communication between neurons in the brain.

"There is more and more information pointing to glutamate as having a significant role in antidepressant-treatment outcomes," said Dr. Gonzalo Laje, one of the study's authors. "We're going to hear a lot more about it in upcoming years."

The researchers looked at more than 700 gene sites, looking for differences between the 6 percent of patients who reported suicidal ideation and the rest of the trial population. Laje cautioned that this study and one that will be published in early October must be replicated, but said the work was an important step toward personalizing treatment for people suffering from depression.

Over the last several years, studies have shown an increase in suicidal thinking among young people who take antidepressants. In 2004, the FDA required that antidepressants be labeled with a black-box warning about such risks. Data later showed a jump in suicides among teenagers that year. It's too early know for sure what created the spike, although some researchers have suggested that a drop in teen antidepressant use contributed to the problem.