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?
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 month, trying several antidepressants, and it’s “hit and miss,” acknowledges Dr. Peggy Richter, head of the Fredrick W. Thompson Anxiety Disorders Centre at Sunnybrook Health Sciences Centre.
Doctors have simply 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 may help to determine the right drug and the right dose for a patient.
“It could be called a revolution in how physicians write prescriptions because this is a whole new world of information about how an individual person responds or does not respond to a medication,” says James Kennedy, head of the Tanenbaum Centre for Pharmacogenetics at the Centre for Addiction and Mental Health (CAMH) in Toronto.
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 different genes may affect the response to antidepressant and antipsychotic drugs. Some of the genes regulate enzymes in the liver, while others play a role in neurotransmitters, or chemical messengers, in the brain. Still other genes are linked to potentially serious side effects, such as weight gain – a factor that can make it hard for some patients to remain on a drug.
Dr. 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. (All these conditions tend to be treated with the same types of drugs.)
So far, 6,000 patients have volunteered for the seven-year study since recruitment began in 2014.
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 Dr. 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,” says Dr. Richter.
The evidence gathered from the study may help provincial governments decide whether to fund the tests, says Dr. Daniel Mueller, head of the Pharmacogenetics Research Clinic at CAMH. After all, faster recoveries should mean fewer medical appointments and that could translate into significant savings for the health-care system.
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, notes Dr. Mueller. 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.
