THE QUESTION
I suffer from depression and my doctor has already prescribed me several different antidepressant drugs. But none of them seem to help much. Is there an easier way of picking a drug that will work for me without having to try one antidepressant after another?
THE ANSWER
Up to one-third of people don't get any meaningful response when they try an antidepressant for the first time. Another third might feel some improvement in mood. And then there's the third that experiences a complete and sustained recovery.
The process of finding a drug that works can take many months, trying several antidepressants, and it's "hit and miss," acknowledges Dr. Peggy Richter, head of the Frederick W. Thompson Anxiety Disorders Centre at Sunnybrook Health Sciences Centre.
Doctors have lacked a test that could help predict how an individual might react to a particular drug, she explains.
But recent advances in genetic research may finally take some of the guesswork out of prescribing antidepressants and a host of other medications.
In particular, research is shedding light on how people process – or metabolize – drugs at different rates.
What has long been known is that enzymes in the liver metabolize drugs in various ways. In some cases, a drug must be changed by enzymes into a new form before it can be absorbed and used. Furthermore, many drugs must be eventually broken down by enzymes so that they can be excreted from the body.
New research has revealed that a handful of genes code for the enzymes involved in drug metabolism. Some people are born with variants in certain genes that make them slow metabolizers. Others have genetic variations that turn them into fast metabolizers. These genetic differences can have a profound effect on the way people respond to drugs.
For instance, slow metabolizers may take a long time to eliminate a drug, running the risk that it will build up to a potentially harmful level. On the other hand, fast metabolizers might get rid of a drug so quickly that it has little effect when taken at the usual dose. In either case, patients might benefit from a drug dosage that's different from the standard treatment in order to account for their genetics. And, for some patients, their genetic makeup means they won't benefit at all from certain medications or suffer significant side effects – regardless of the dose.
These findings are fuelling the development of a new field of medicine known as pharmacogenetics, in which genes help to determine the right drug and the right dose for a patient.
"It could be called a revolution in how physicians write prescriptions," says James Kennedy, head of the Tanenbaum Centre for Pharmacogenetics at the Centre for Addiction and Mental Health (CAMH).
Numerous companies and some health-care facilities are already promoting genetic tests that promise to predict a patient's response to various drugs, including antidepressants, pain relievers and heart medications.
The tests range in price from a few hundred to several thousand dollars. Most of them aren't commercially available in Canada, although some private clinics will send your DNA (contained in a saliva sample) to U.S. labs for analysis.
However, there's a catch. Most of the tests have not been extensively studied, so their reliability is unknown.
For that reason, CAMH has joined forces with Assurex Health, a U.S.-based company, to study how a variety of genes may affect the response to antidepressant and antipsychotic drugs.
Kennedy says the researchers hope to recruit up to 20,000 Ontario patients who suffer from depression or related conditions such as anxiety and obsessive-compulsive disorder.
The goal of the research is to determine if the use of this specific test can help speed up the recovery of patients and, in turn, save the health-care system money, says Richter, who has been recruiting volunteers among her patients at Sunnybrook.
"By choosing the right drug and the right dose at the start, it could have a huge impact on patients and the health-care system," Richter SAYS.
The evidence gathered from the study may help provincial governments decide whether to fund the tests, says Daniel Mueller, head of the Pharmacogenetics Research Clinic at CAMH.
The researchers are quick to point out that a genetic test – even if successful – won't be a panacea. Depression is a complex condition with many different causes. Some patients may benefit from non-drug treatments, such as psychotherapy, Mueller notes. So, doctors would still need to rely on their own clinical judgment for selecting the most appropriate therapy for each patient, he says.
But, at the very least, the tests might help identify patients who are less likely to respond well to certain medications because of their genetic makeup. That alone would be a significant improvement for some patients who now languish for months on ineffective treatments.
Paul Taylor is a patient navigation advisor at Sunnybrook Health Sciences Centre. He is a former Health Editor of The Globe and Mail. You can find him on Twitter @epaultaylor and online at Sunnybrook's Your Health Matters.