Medical Edge Newspaper Column

Genetic Test Can Help Physician Determine Appropriate Depression Medication

March 6, 2009
Dear Mayo Clinic:
I have read that genetic testing — I think it's called CYP testing — can determine if certain antidepressants will work for people who have depression. If so, would you explain the concept and also name the antidepressants for which genetic testing exists?

Answer:
Testing is available to help your physician select a medication for depression. The results from this type of genetic testing, called pharmacogenomic testing, don't pinpoint the exact medication that will work for you. But results help your doctor avoid medications that are least likely to be helpful.

Here's how it works. Cytochrome P450 (CYP) genotyping evaluates how two or three genes in the CYP family affect your body's metabolism of antidepressant medications. Most antidepressant medications are metabolized by CYP enzymes.

The testing predicts an individual's metabolism of antidepressants in these categories:

• Selective serotonin reuptake inhibitors (SSRIs), usually the first choice for depression treatment. Examples are fluoxetine (Prozac, Sarafem), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa) and escitalopram (Lexapro).

• Tricyclic antidepressants, typically used when SSRIs aren't effective. Examples include amitriptyline (Elavil), amoxapine, desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil, Tofranil-PM) and nortriptyline (Pamelor).

Based on the results of CYP testing, your doctor will know if your metabolism of a given medication is:

• Normal, indicating that the medication is likely to be helpful without significant side effects
• Intermediate, indicating that you might benefit from a reduced dose
• Poor, meaning that the drug stays in your system too long and can cause troublesome side effects. Side effects from antidepressants can include headache, nausea, insomnia, agitation, dry mouth, constipation, and many others.
• Fast (also called ultrarapid), limiting the benefit from the medication because it's out of your system too quickly.

Additional pharmacogenomic testing also is available that focuses on how a medication interacts with its intended target. For example, SSRIs are active at the serotonin transporter in the brain. Genetic variation of that gene can affect the ability of people to respond to SSRIs.

Your doctor looks at all this information to select the medication most likely to offer you relief from depression symptoms without side effects and to help determine an optimal dosage.

For example, if you are a poor metabolizer for the enzyme CYP2D6 and if you are given a normal dose of fluoxetine, your blood level of this medication might be elevated to toxic levels, causing side effects. Knowing this, your doctor would recommend a drug that is not metabolized by CYP2D6, for example, citalopram or escitalopram, assuming your ability to metabolize these drugs is predicted to be normal by CYP2C19 testing.

If you are considering medication for depression, or have taken antidepressants and didn't improve, ask your doctor about pharmacogenomic testing. The testing can shorten time required to find the medication that improves symptoms without troublesome side effects. That trial-and-error period can delay your recovery in part because it can take eight to 12 weeks for some antidepressants to be fully effective.

The test is easy to perform. It requires a blood draw, with a sample sent to a laboratory for analysis.

CYP testing has been available for about four years. Because it's relatively new, not all doctors and clinics offer it. One barrier is that there's a learning curve to interpreting the results. Interpretation is more complicated for patients who take several medications.

New tools are being developed (one at Mayo Clinic*) that will make results easier to interpret quickly. As those tools become more widely available, I believe doctors will increasingly view this testing as an important and helpful tool for treating patients with depression.

—John Black, M.D., Psychiatry, Mayo Clinic, Rochester, Minn.

*Disclosure: John Black, M.D., and colleagues have developed a psychiatric pharmacogenomic treatment algorithm that has been licensed to AssureRx. Dr. Black has received no royalties from the license to date but may in the future. Mayo Clinic also has an equity stake in this company.