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Genes May Alter Antidepressants' Effects

Variations in certain genes may affect how well depressed people respond to different antidepressants, new research shows.

The report comes from Francis McMahon, M.D., of the National Institute of Mental Health (NIMH).

"Medications to treat depression are widely available, but no one treatment works for everyone," McMahon says in a news release

There is no test to predict which of the various antidepressants will work best for a particular patient. It can take trial and error over weeks or months to find the right one. "We are seeking to better understand why this is the case, and, using genetic markers, develop personalized treatments that give patients the best chance at remission," McMahon says.

"Ultimately, our goal is to put together a panel of genetic markers that can guide treatment decisions and help doctors choose an antidepressant that will work best for an individual patient," he says. That panel of genetic markers isn't complete yet. But McMahon's findings may help.

McMahon studied data from 1,953 adult patients treated with the antidepressant Celexa.
The patients' genes were screened. Certain variations in two genes were associated with response to Celexa treatment.

One of those genes is the HTR2A gene, which is linked to serotonin, a brain chemical boosted by some antidepressants, including Celexa. The other gene, called GRlK4, is linked to glutamate, another brain chemical.

Along with past research, the data "make a compelling case for key roles of HTR2A and GRlK4 in the mechanism of antidepressant action," writes McMahon. "Genetic markers that identify individuals at high risk for treatment failure or particular side effects may ultimately help guide treatment decisions," he writes.

McMahon's findings were presented in Hollywood, Fla., at the American College of Neuropsychopharmacology's annual meeting.

Depression is a common but often treatable disease. In any year, about 21 million U.S. adults — nearly one in 10 — are depressed, according to the NIMH.

The NIMH lists these warning signs of depression:

  • Persistent sad, anxious, or "empty" mood
  • Feeling hopeless or pessimistic
  • Feelings of guilt, worthlessness, helplessness
  • Loss of interest or pleasure in hobbies and activities that were once enjoyed (including sex)
  • Fatigue, decreased energy, or feeling "slowed down"
  • Difficulty concentrating, remembering, making decisions
  • Sleep problems, including insomnia or sleeping too much
  • Changes in appetite and/or weight
  • Thoughts of death or suicide; suicide attempts
  • Restlessness, irritability
  • Persistent physical symptoms that don't respond to treatment, such as headaches, digestive disorders, and chronic pain

    The exact cause of depression isn't known. It may be a combination of genetic and environmental factors. If you suspect depression, seek help. Talk to your doctor for depression screening. Treatments may include medications and/or talk therapy.

    If you already know you have depression, you may want to use these tips from the NIMH:

  • Set realistic goals.
  • Break large tasks into small ones, set priorities, and do what you can.
  • Try to be with other people and confide in someone. It's usually better than being alone and secretive.
  • Participate in activities that make you feel better.
  • Mild exercise, going to a movie or ballgame, or participating in religious or social activities may help.
  • Expect your mood to improve gradually, not immediately. Feeling better takes time.
  • Postpone important decisions until the depression has lifted.
  • Let your family and friends help you.

    Remember that positive thinking will replace the negative thinking that's part of the depression as your condition responds to treatment.

    The NIMH offers these do's and don'ts for people who have a depressed friend or family member:

  • Do help the depressed person get an appropriate diagnosis and treatment.
  • Do encourage the person to give treatment a chance and to seek different treatment if needed.
  • Do offer emotional support.
  • Do talk with your friend or relative and listen carefully to them.
  • Do invite the depressed person for walks, outings, or other activities.
  • Do encourage the person to participate in activities he or she once enjoyed.
  • Don't ignore remarks about suicide. Report those remarks to the patient's therapist.
  • Don't push the depressed person to do too much, too soon.
  • Don't accuse your depressed friend or relative of faking illness or being lazy.
  • Don't expect a depressed friend or relative to "snap out of it."

    SOURCES: American College of Neuropsychopharmacology's annual meeting, Hollywood, Fla., Dec. 3-7, 2006. News release, GYMR. National Institute of Mental Health: "Depression."

    By Miranda Hitti
    Reviewed by Louise Chang, M.D