New genetic analysis greatly reduces trial-and-error prescribing…

When a doctor prescribes an antidepressant for a patient who is suffering from depression, there are well over a dozen options to choose from. But none of these drugs works for everyone. And an antidepressant that works well for one person may cause severe or unacceptable side effects (such as headache or nausea) in another person.

Until recently, finding the right antidepressant for each patient has usually involved a considerable amount of trial and error. The process might take weeks and be particularly frustrating for the person suffering from depression.

Now: Doctors are increasingly turning to a more personalized way to tailor the prescription to the patient. With an emerging field known as pharmacogenetics, doctors can test your genes to determine which antidepressant best fits your personal genetic makeup.


Other factors (such as one’s stress levels and overall physical condition) also come into play, but much of your response to antidepressants—and to many other drugs—is determined by your genes.

How your body deals with medication involves two processes… 

  • Pharmacokinetics refers to the way your body metabolizes drugs, altering them chemically so they can have their desired effect on you and breaking them down to be eliminated. This reaction determines the level of the medication in your body as well as its level of effectiveness for you.
  • Pharmacodynamics is the way drugs interact with specific proteins in your cells—that is, speeding them up, slowing them down and/or altering the flow of chemical messengers between them. Such changes are the basis of benefits and risks from individual drugs.

In recent years, scientists have identified a number of genes that govern these processes and learned how variations in these genes (or “variants”) affect drug response. All proteins in the body are encoded by their genes. While this type of genetic analysis cannot eliminate trial and error altogether, it gives doctors a valuable head start at predicting which antidepressants (and doses) are likely to work well while causing the fewest side effects.


To predict your response to an antidepressant and your odds of experiencing side effects, your doctor can order a blood test or do a swab to collect a sample of cells from the inside of your cheek. A laboratory analysis would look for a family of enzymes, known as cytochrome P450 (CYP) enzymes, that are produced primarily in the liver and play a major role in metabolizing many drugs—including about 20 antidepressants.

Dozens of CYP enzymes, which are encoded by our genes, have been identified, but only a handful are active in metabolizing antidepressants. Most people have two, in particular, which are important in breaking down some of the most widely used antidepressants…

  • Cytochrome P450 2D6 (CYP2D6) is a key enzyme for antidepressants including fluoxetine (Prozac) and paroxetine (Paxil).
  • Cytochrome P450 2C19 (CYP2C19) is the enzyme for antidepressants such as citalopram (Celexa) and escitalopram (Lexapro).

Depending on which gene variants you’ve inherited, testing may show how quickly you’ll metabolize these and other antidepressants.

Genetic analysis also gives information on how your brain cells are likely to respond to medication. Many antidepressants, including sertraline (Zoloft) as well as Prozac, Paxil, Celexa and Lexapro, work primarily by increasing activity of the neurotransmitter serotonin. Genes that influence how brain cells interact with serotonin have been identified. Also: If your genes suggest that your brain cells are unlikely to be strongly affected by serotonin-only drugs, you may do better with an antidepressant that also works on other neurotransmitters, such as venlafaxine (Effexor) or duloxetine (Cymbalta).


Because genetic testing is still relatively new in psychiatry, you may have to mention it to your doctor. It’s worth considering for…

  • The very young or very old, who might have trouble communicating how the drug is affecting them.
  • People with very severe depression…or if suicide is a risk—when it’s especially important to get the drug right the first time.
  • People who have been prescribed medication (such as prescription painkillers) in the past that did not work or produced severe side effects at low doses.
  • People whose close family members have suffered significant side effects from medication, particularly antidepressants.

Note: People who are already taking an antidepressant may also benefit from testing if they are not achieving a desired response and/or experiencing side effects.

How to get tested…

If you opt for genetic analysis, your doctor will order the test. Local and regional laboratories, even large ones, may not do genetic testing, but they can send blood or cheek swab samples to a lab that specializes in this work.

If there is a university medical center in your area, a doctor there who prescribes antidepressants may be able to help you with testing. 

Important: Because most physicians are not trained to interpret genetic test results, look for a company whose report translates findings into recommendations for antidepressant prescriptions and doses for your doctor. Such reports are available when the analysis is performed by Assurex Health, Genelex, Genomind and Mayo Clinic.

The cost for this type of genetic testing may range from several hundred to several thousand dollars. Health insurers vary in their willingness to cover this type of testing, so check in advance to find out whether you’ll be reimbursed. If your insurer denies coverage, consider asking your doctor to write a letter explaining why the testing is needed and/or filing an appeal.