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Genetics may bring out the dark side of antidepressants

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A new test uses genetic data to fight patients' risk of drug-reactive suicide

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For years, it's been a controversial side effect of antidepressants: for all the patients helped by the drugs, there was a smaller cohort for whom the beginning of treatment triggered a descent into thoughts of suicide. Actual suicides are rare, but suicidal ideation can emerge in as many as one in twelve patients, most commonly in their first months on the drugs. Doctors can monitor for the side effects, but it's been a persistent danger, even as antidepressant use has skyrocketed.

A persistent danger, even as antidepressant use has skyrocketed

A new test being developed by Sundance Diagnostics promises a different tactic. Scientists at the Max Planck Institute isolated 79 genetic markers correlated with an increased risk of antidepressant-induced suicide risk. Taken together, the latest tests show a 91 percent chance of identifying in advance whether antidepressants will trigger suicidal thoughts in a patient taking SSRI-based antidepressants. If the results hold, such a test would let doctors prescribe the drugs with much less fear of an unknown. "It is very important not to deprive patients of antidepressants because of this side effect," says Andreas Menke, a lead researcher on the study, "but to identify patients at risk and provide these patients at risk with closer monitoring."

"This is something we've been looking for in the field for a long time."

It will take at least another year and a half to conduct the tests necessary for FDA approval, which will test out the markers in a much broader human population over a longer period of time. In the meantime, the lab-developed version may be trickling out to doctors over the next few months. And the test certainly has the potential to find a big market: 11 percent of Americans over the age of 12 takes some form of antidepressant, according to a 2011 study from the US Centers for Disease Control and Prevention, but there's still no proven way to predict or guard against suicidal side effects. For the most part, it’s left to patients to self-monitor and self-report. A precautionary test could become standard practice whenever an antidepressant is prescribed. "This is something we've been looking for in the field for a long time," says Sundance's consulting doctor Peter Tolias.

The most convincing result so far

This isn't the first time researchers have found genetic factors for suicide risk, but a number of components make it the most convincing result so far. After finding the markers, researchers at Max Planck replicated the results at an independent lab with a separate group of 501 human subjects, giving doctors confidence the results will hold up under wider distribution. The markers are also seen as particularly plausible because many are already associated with neurological effects, making them plausible triggers for an unforeseen neurochemical side effect. The combination was enough to convince Sundance to invest in bringing the test to market.

For researchers, the markers feel like a vindication

More importantly, recent legal battles have cleared the way for such a test. The Planck work is fundamentally a genetic discovery, but a Supreme Court decision in June offered companies like Sundance a clearer path to market. The current law doesn’t allow for the markers themselves to be patented, but the Planck Institute can apply for patents on the process by which the markers are tested, or any synthetic proteins used in the test. They don’t have complete rights to the process — someone else could always reverse-engineer a new test that targets the same markers — but there’s enough of a head start to spur investment.

Still, for doctors who have lobbied for years to establish the suicidality reaction as science, establishing genetic markers feels like a vindication. David Healy, a long-time suicidality researcher who’s consulted with Sundance in the past, says the genetic factor gives an important new edge on the problem. "I think it's highly likely there are genes that are risk factors for becoming suicidal on antidepressants," Healy says. "I suspect there will be a number of genes involved in any one person becoming suicidal and the package or genetic markers that works for you might not work for me." Sundance’s 79 markers are just the first batch — but they’re the best we’ve got so far.