Category

Pharmacogenomics

Pharmacogenetic Testing May Change Psychiatric Treatments for ADHD, Depression

by John M. Grohol, Psy.D.

Prescribing medications has long been a trial-and-error approach for nearly any medication you could take. That’s been especially true in psychiatry, where there are dozens of medications that could be prescribed for common mental health concerns, such as anxiety, depression and attention deficit hyperactivity disorder (ADHD).

What if doctors had a better idea ahead of time which medications may work better for you than others, based upon your unique biology and biochemical makeup? They could then make prescribing decisions with a lot more knowledge, finding you a medication that would have a higher chance of working the first time.

This process is called pharmacogenetic testing — and it’s time is fast approaching.

Pharmacogenetic testing is the process of examining a person’s unique genetic structure to help determine what medication will metabolize best within that person’s system. The idea of personalized medicine like this has been around since the 1950s. But it hasn’t been until very recently that such genetic testing became inexpensive enough to make it within reach to millions.

Today, if you go into your doctor and say, “Hey doc, I’m depressed,” she’ll run through the list of symptoms of depression and determine if you actually meet the diagnostic criteria for depression. After some additional questioning and a discussion about your treatment plan, she may decide to prescribe you an antidepressant. She’ll typically choose that antidepressant from a list of more than a dozen different varieties, largely based upon her own professional experience in prescribing these different antidepressants.

Will It Work For Me?

Your symptoms are a part of the equation, but they won’t answer the most important question you should have when being prescribed an antidepressant — will it work for me?

Because research shows that after your first antidepressant prescription, less than 1 in 5 people will experience a positive effect from that medication. That means the vast majority of folks — 4 out of 5 — will experience no or little relief from their depressive symptoms.

That’s because medications today are largely prescribed randomly, with little regard to your biochemical and genetic makeup. This means that what works for someone else may very well not work for you. In short, it’s a pretty horribly random way to practice medicine.

Pharmacogenetic Testing to the Rescue

Pharmacogenetic testing can help us practice better medicine by having at least some idea about what medications may have potentially a great impact on your biochemistry.

There are at least two pharmacogenetic tests for ADHD. One is by a company called Harmonyx that just became available, and another is available from AssureRx. Some hospital systems, such as Duke, also can do in-house testing in their own labs. These kinds of tests usually cost less than $100 (paid out of your own pocket, typically), and will return a list of drugs, in order of their likely effectiveness for a given condition. AssureRx also offers a similar test for people with depression.

This area is still in its infancy, however. Pharmacogenetic testing is not a cure-all, and it won’t guarantee that even if you try the first medication at the top of your personal list, it will work and be effective for your ADHD or depression symptoms (other disorders will be forthcoming in future years).

But it’s an exciting development in the world of personalized medicine and improving the effectiveness of our existing treatments.

Getting Pharmacogenomics Into the Clinic

by Jennifer Abbasi

What if there were a way to know if a depressed patient would respond to an antidepressant—before it was prescribed? Or to predict a bleeding event from an antiplatelet therapy? In recent years, advances in genetic testing have made such drug-response predictions possible for patients with certain gene variants. But physician adoption is moving slowly, say experts in the growing field of pharmacogenomics.

“While we’ve made tremendous rapid advances in terms of basic science and technological advances, and [while] clinical outcomes [are] there for some gene-drug pairs, clinical implementation unfortunately has been lagging behind,” said Edith A. Nutescu, PharmD, MS CTS, associate professor and director of the Center for Pharmacoepidemiology and Pharmacoeconomic Research at the University of Illinois at Chicago College of Pharmacy.

Advances in genetic research may allow for more targeted medication prescriptions

by Paul Taylor

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.

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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.

7 Things to Know About Pharmacogenomics

By Mark Dunnenberger

We all know a medication that works well for one person might not work for another – or even cause some people unwanted side effects. These differences in response can be caused by factors such as age, gender or other drugs and supplements that a person might be taking.

However, up to 99 percent of us may have small variations in our genes that can also impact how we react to common medications, including pain relievers, antidepressants and blood thinners.

Now, through a new kind of genetic testing in a field known as pharmacogenomics, some doctors are able to identify a number of these variations to help predict how their patients might respond to a new medication.

These tests are very different than genome sequencing services that provide data on your ancestry, analysis of disease-related genes or information on your risk of developing certain diseases. Instead, the tests look for specific gene variants that can help physicians minimize the trial and error of prescribing certain medications and help narrow down medication choices, especially when it comes to treatments for pain and psychiatric medications.

When I helped open the pharmacogenomics clinic at NorthShore University HealthSystem in Evanston, Illinois, in 2015, it was the first hospital-based pharmacogenomics clinic of its kind. Now, a small but increasing number of doctors and health systems are offering this testing to patients. Some direct-to-consumer testing companies also offer pharmacogenomics tests.

However, pharmacogenomics is a relatively new field, and not every doctor has access to a pharmacogenomics test or knows how to interpret the genomic information. Additionally, only about 20 percent of the drug market has been impacted by pharmacogenomics so far. For many medications, a pharmacogenomics link has not yet been found or doesn’t exist.

Understanding the basics of pharmacogenomics and how it differs from other genetic tests can help you decide whether or not these tests could be a useful tool for you and your doctor. Here’s what to know:

1. Pharmacogenomics will not tell you why your eyes are blue or predict your risk of cancer. Unlike other genetic tests, pharmacogenomics does not measure disease risk. Instead, it helps doctors identify treatments that are most likely to work by examining how your genes affect your response to medications.

[See: 5 Common Preventable Medical Errors.]

2. The tests cannot give information about how you may respond to every single medication. Currently, research only supports testing for certain drugs, most commonly those for cardiology, pain management and depression/mental illness.

3. A pharmacogenomics test has value throughout your life. By studying a set of your genes, clinical experts can analyze a broad amount of information regarding drug therapy for many conditions, including psychiatric disorders, pain management and cardiology. Because your genes don’t change over time, you only need one test to discover genetic information that could be applied to future care. At some hospital-based testing centers, results can be added to your electronic medical record for easy access and used as a reference for medication and treatment choices throughout your life.

4. Pharmacogenomics is especially helpful for non-responders – people who have tried numerous drugs to find ones that effectively treat their symptoms. For some people, the tests can help explain why they didn’t respond to medications in the past, or provide peace of mind in knowing they are not genetically predisposed to a negative outcome on a new medication.

5. To make the best use of pharmacogenomics testing, have a goal in mind. Make sure that the medications covered by the genes being tested are related to your current clinical situations or medications you and your doctors are considering for future use. For example, if heart disease runs in your family, the goal of the test might be to look at the genes related to cholesterol lowering or blood thinning medications, as your doctor might consider these in your future care.

[See: How to Help Aging Parents Manage Medications.]

6. Pharmacogenomics is “not a crystal ball.” While it could determine why your medication isn’t working and help narrow down your options, it won’t tell you the perfect drug for your condition or provide information on drug-drug interactions or drug supplement interactions. Rather, it can narrow down your options and help doctors prescribe the right medicine faster.

7. With diagnostic tests, sometimes no news is good news. Often doctors recommend the genomic testing to rule out genetic factors as the culprit if there are concerns about medication response. No specific feedback from your genomics test means that your suboptimal response to a particular medication is not the result of your genetics, but could be caused by other factors such as diet or age.

At our pharmacogenomics clinic, testing is a two-day process that begins with a session to lay out considerations for the patient. We discuss the benefits, limitations, risks and cost so the patient can make a value-based judgment with a clear understanding of what information the test will and won’t provide.

[See: 10 Lessons From Empowered Patients.]

Especially when it comes to pain medication and psychiatric medications, pharmacogenomics testing can minimize the trial and error of prescribing medications, plus help a physician to narrow down treatment choices. For some people, knowing can mean a lot. For others, it just might not be valuable for their particular situation or condition. If you think pharmacogenomics testing could help you, work with a clinician who has expertise in analyzing pharmacogenomics test results for your particular condition or who can partner with pharmacogenomics experts. This is the best way to determine whether this particular type of genetic testing is likely to provide you actionable results or peace of mind.

Mark Dunnenberger, PharmD, leads the nation’s first dedicated pharmacogenomics clinic, started last year, within the Center for Personalized Medicine at NorthShore University HealthSystem in Evanston, Illinois.