Pharmacogenomics have the potential to revolutionize antidepressant prescribing

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By Kyle Brutman

A recent study showed that the use of selective serotonin reuptake inhibitors (SSRIs) and other types of antidepressants could become more common among the college student population.

According to a 2012 survey by the Association for University and College Counseling Center Directors, the two mental health issues that are the most prevalent among college students are anxiety and depression. Anxiety was presented as a concern to 41.6 percent of college students, the highest number on the list — depression followed at 36.4 percent.

Thirteen percent of Americans rely on antidepressants to alleviate the symptoms that are associated with depression, social anxiety disorder and other mental conditions, according to a 2013 news release from the Mayo Clinic.

The results from taking antidepressants vary, depending on the individual, but whoever takes an antidepressant such as Prozac, a medication that fights depression by altering serotonin levels in the brain, puts themselves at risk of experiencing a number of side effects. They include decreased sex drive, irregular heart rate, suicidal thoughts and seizures, among others. It is worth noting that SSRIs, such as Prozac, feature fewer side effects compared with other antidepressant classes.

The side effects associated with antidepressants can be severe, but pharmacogenomics has the ability to help predict whether or not they might occur.

A method that dates back to 510 B.C., when Pythagoras noticed that the act of consuming fava beans was fatal in only certain individuals, pharmacogenomics explores how drugs are affected by a user’s genetic makeup. More specifically, this concept looks to develop drugs that are tailor-made to adhere with a person’s genotype.

Pharmacogenomics is a work in progress, and has been for years, but there have been advances in the field during the last decade.

The AmpliChip CYP450 Test became the first FDA-approved pharmacogenomics test in 2004, and has been at the center of the field ever since.

According to Martin Zdanowicz, the Associate Dean for Health Studies at the University of Miami, the device has the ability, using microarray technology, to look at thousands upon thousands of genes at one time in order to find genetic variation.

Previous technologies required a lot more time and a lot more money.

“The application has come a long way to really starting to impact clinical practice for the first time in quite some time,” Zdanowicz says.

The goal of pharmacogenomics is to eliminate the “hit and miss” process that a user  oftentimes meets when obtaining an initial prescription.

While the science hasn’t reached its potential yet, treatments for breast, colon, lung and other cancers, as well as leukemia, have been on the forefront of pharmacogenomics. This is because the targets that are responsible for destroying the cancer inside the body are more easily identifiable.

However, medications designed to treat depression and anxiety present a much more difficult challenge for those in the field.

Antidepressants and anti-anxiety agents are among the hardest drugs to test for in pharmacogenomics.

Zdanowicz says that treating depression requires at least three known targets to understand which drug a user may need: liver enzymes, which break down the drug; serotonin transporters, which may cause disruptions in serotonergic system if it malfunctions; and serotonin receptors, which can, when bound, increase or decrease antidepressant effects.

Serotonin is a chemical in the brain that helps nerves cells communicate with each other. If serotonin is not properly located within the brain, there will be improper communication between brain cells, and subsequent depression may result.

If a person doesn’t respond positively to a pharmacogenomically recommended antidepressant, Zdanowicz says, there can be an issue with any of the targets that were tested, which can cost a lot of money to test for.

He says that there is a small sample size of antidepressant testing in pharmacogenomics, and the tests that have been conducted have shown to result in relatively minor improvements, but not nearly enough to invest an enormous amount of money into, yet.

The current state of antidepressants features multiple classes of medications, giving doctors great flexibility in choosing which antidepressant to prescribe. On the contrary, a physician may have to go through multiple antidepressant in order to find one that is the right fit for the patient.

Despite depression’s current limited application within pharmacogenomics, a San Diego-based company called Pathway Genomics has developed a process called Mental Health DNA Insight, which uses a patient’s blood or saliva to obtain his or her genotype to help determine the best antidepressant for the individual. The test can predict how a genotype responds to 50 different psychiatric medications. Mental Health DNA Insight places each drug into one of four categories (preferential use, use as directed, may have significant limitations, or may cause serious adverse effects) an explanation of the placement.

The current herd of college students in the medical field should have a general knowledge of pharmacogenomics, says Zdanowicz — that’s how big the science has become.

He says that he used rats and mice when studying the area in college, but there has

since been a change, from rats to cells to DNA replication, and, now, genes.

“The whole progression has moved away from the big picture now to the very, very small level,” Zdanowicz says.

And with a changing view of mental health among the current college generation, there is a chance that depression and anxiety disorders may become a priority in pharmacogenomics. According to a Harris Poll, just 3 percent of college-aged students (aged 18-25) view physical health as a more important aspect of health than mental health.

“In terms of overall clinical impact, pharmacogenomics is still relatively quite limited,” Zdanowicz says with respect to the treatment of depression.

“We’ll keep going forward. I definitely think some good things are going to come from it.”

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