Posted by jrbecker on November 28, 2004, at 17:11:52
Last update: November 27, 2004 at 10:49 PM
THE RIGHT DRUG? ASK YOUR DNA
Maura Lerner
Star Tribune
Published November 28, 2004
startribune.comPsychiatrists at the Mayo Clinic have come up with a new way to help people avoid some of the nasty side effects of antidepressants and other drugs.
They're using genetic tests to predict which patients are likely to get headaches, nausea or other problems from medications such as Prozac and Paxil. And they're changing their treatment accordingly.
The tests are among the first in a new wave of genetic tools that, experts say, will transform the way doctors make decisions about treating their patients.
"At this point in time, the test really can't tell you what drug will work," said Dr. David Mrazek, Mayo's chief of psychiatry, who has led the charge for genetic testing. But "it will identify drugs that don't work." And that, he says, can help reduce side effects and failure rates.
In effect, the DNA tests look for faulty genes that can interfere with someone's ability to process drugs normally. Doctors can use the information to adjust dosing levels or steer people away from drugs that may harm them or can't help them.
Mayo is one of the few medical centers in the country using such DNA tests as part of routine medical treatment. So far, the testing is limited to psychiatry and a few other fields. But experts say that may change soon.
"It's the science fiction of the near future, the very near future," said Dr. Karen Dickson, a New Brighton psychiatrist and past president of the Minnesota Psychiatric Society. "We'd love to be able to pick antidepressants and avoid the side effects and the nonresponders. We would save a lot of time and money, and get people better faster."
Already, psychiatrists at the Minneapolis Veterans Medical Center are working on a plan to start offering DNA tests to some of their patients.
And last month, Dr. Francis Collins, the director of the National Human Genome Research Institute, predicted that tests like this will spread fast. "Do not be surprised," he told a conference of family physicians, "if in the next year or two, this kind of DNA testing will be considered as a necessary step before writing a prescription."
Long-known problem
Doctors have long known that some people are better able to handle certain medications than others. But in the last few years, scientists have started closing in on which genetic differences are at play.
At Mayo, Mrazek and his colleagues have focused on genes for a family of enzymes known as cytochrome P450. Those enzymes control how the body processes dozens of medications, including some antidepressants, heart drugs and cancer drugs. If those genes don't work right, the body's ability to metabolize drugs -- to use them and dispose of them -- goes haywire.
For some patients, this translates into years of frustration, searching for a drug that works and won't make them sick.
By the time one woman came to see him, Mrazek recalled, she had spent about 10 years seeking help for her depression. She claimed that every antidepressant she tried caused excruciating headaches or other problems. Her doctors would roll their eyes and scold her for not taking her medication.
When she had the DNA test, Mrazek said, he discovered that she was a classic "poor metabolizer." Because of faulty genes, she couldn't produce a key enzyme, known as 2D6, which helps break down certain drugs in the body. Without the enzyme, the antidepressants built up in her bloodstream like a toxic overdose, triggering the side effects.
He switched her to a different drug that didn't need that enzyme to function. And her relief was palpable. "This is the reaction I have over and over again -- 'We're not crazy. We're not hypochondriacs,' " Mrazek said. "They feel like they've been sort of mishandled by doctors who haven't listened to them."
Many give up
Many depressed people simply stop taking their drugs because of side effects, experts say.
So for patients, this kind of test could be a dream come true, according to Sue Abderholden, executive director of the National Alliance for the Mentally Ill, Minnesota chapter. "If we could reduce the side effects -- boy, that would be huge."
At the other extreme, some patients don't benefit at all from certain antidepressants, at least at standard doses. In those cases, Mrazek says, they may have too many copies of a certain gene, which results in a surplus of enzymes working overtime to clear the medicine out of their bodies. They may need a bigger dose than normal, or a different drug.
This kind of test won't prevent all side effects, he notes. For example, antidepressants have been linked to an increase in suicidal thoughts, and he said genes may have little or nothing to do with that. But genetic differences are clearly to blame for other types of side effects, such as impotence or loss of sex drive.
Generally, most people tolerate these drugs well, he adds. Only about one in 10 people may have a genetic variation that causes a problem, though the rates vary by race, geographic origin and the type of drug involved.
The DNA test Mrazek uses is a simple blood test and needs to be done only once in a lifetime. But some worry about the costs. At the Mayo Clinic, it's about $650 to test just two key genes.
That's one problem psychiatrists at the Veterans Medical Center in Minneapolis are wrestling with as they prepare to start offering the tests. "Depression is such a common thing. If you start doing this indiscriminately, it's a lot of cost," said Dr. Adityanjee, a VA psychiatrist who is part of a committee studying the DNA testing. For now, he said, they'll probably limit it to certain patients, such as those who have had problems with medications in the past. "It's too early at this point in time for this to be part of, let's say, gold-standard treatment," said Adityanjee, who uses only one name.
But as costs drop and more tests become available, he predicts, "It will become part of our day-to-day treatment."
For Mrazek, it already is.
He started developing the test when he joined the Mayo Clinic in 2000, after years as head of psychiatry at George Washington University in Washington, D.C.
He knew that Mayo already had a reputation as a leader in the field. For more than a decade, its doctors have been testing children with leukemia to see how they metabolize drugs, to make sure they can tolerate a common anticancer drug.
At first, Mrazek said, some of his colleagues were skeptical about the need for genetic testing in psychiatry. And even he thought he would use it sparingly at first, when patients ran into trouble with their medications. But "it didn't take me very long to say, 'well, wait a second, why don't I do the test first?' " he said. Now, he says, "it's very hard for me to think about prescribing without it."
He and other Mayo psychiatrists have been offering it to patients on a routine basis since February 2003.
Mayo is also offering the test commercially, to doctors and clinics around the world.
Eventually, Mrazek hopes to fine-tune the tests to be able to predict which drugs will work best for each patient. "We're not there now," he said. But he's optimistic: "I think it will happen in the next five, 10 years."
Maura Lerner is at mlerner@startribune.com.
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