Gene variant affects response to antidepressants

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Individuals with depression and anxiety respond better to antidepressant medication if they carry a mutation in a gene called CRHR1, results of a study indicate.

This finding is “very relevant,” Dr. Julio Licinio told AMN Health, “because the next generation of antidepressants is targeted exactly at this gene. Our study puts even more of an emphasis on this target for antidepressant development.”

Licinio, at the David Geffen School of Medicine, UCLA, and his associates looked for associations between CRHR1 mutations and the response to fluoxetine, the generic name for Prozac, and desipramine in 80 depressed Mexican-Americans.

They found that a certain mutation of CRHR1 was associated with a 70 percent greater reduction in anxiety and a 31 percent greater reduction in depression after treatment with either fluoxetine or desipramine in patients with both high anxiety and high depression scores.

In contrast, this mutation did not seem to benefit people with only low levels of anxiety or depression, the team reports in the journal Molecular Psychiatry.

If these findings can be verified, they would support the theory that response to antidepressant drugs varies from one person to the next and that the CRHR1 gene and possibly others are involved, the investigators say.

This could have major implications for patients with anxiety and depression, Licinio said, explaining that “right now, depression treatment is basically trial and error—you try one drug for about 6 to 8 weeks and if it doesn’t work you try another. It is a very tedious process and many patients drop out of treatment if the first drug doesn’t work.”

The current work holds the promise of tailored antidepressant therapy based on a patient’s individual genetic makeup, he pointed out.

SOURCE: Molecular Psychiatry, December 2004.

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