Meds

Using genes to choose the best antidepressant.

Early studies show potential for profiling treatment based on genetics. Genes reveal likely response to antidepressants
Roxanne Khamsi

Close scrutiny of patients’ genes could help identify the most effective antidepressant medication for each individual, according to two separate studies.

This tailored approach could one day reduce the guesswork involved in treating people with depression, the researchers say. Currently, prescribing medication for the mental illness can be a case of trial and error, before hopefully hitting on a drug that works.

“In the future, all of the treatment options you have will potentially be influenced by genetic information,” says Francis Lee at Weill Medical College, Cornell University in New York, US.

Lee and colleagues investigated a gene mutation that occurs in 20% to 30% of Caucasians. People with this mutation may not respond to fluoxetine, the antidepressant drug sold as Prozac, suggests their study, published in the journal Science.

Nerve plasticity

The researchers used mice which were engineered to carry a human version of the mutated gene, BDNF. When the mice were deliberately stressed by having a bright light shone on them, they took longer to perform a set task.

Giving fluoxetine to mice with two normal copies of BDNF halves the time they take to perform the task. However, the drug had no effect on mice carrying two mutated copies of the gene, the researchers found.

Lee suspects that humans with the same BDNF mutation may not respond well to other antidepressants of the same type, known as selective serotonin reuptake inhibitors (SSRIs). Previous studies have shown that the BDNF gene makes a protein that promotes nerve growth, or nerve “plasticity”, in the brain. “You need plasticity to adapt to stress,” says Lee.

This adaptation might help people overcome depression or post-traumatic stress disorder, he says. “You should learn, for example, that even though 9/11 occurred, it won’t occur again every year on that date.”

Lee speculates that SSRIs somehow boost the presence of BDNF proteins under normal conditions, and that these drugs fail to have a similar effect in people with the gene mutation.

Early days

Another study, published this week in the Journal of the American Medical Association, also shows a link between an individual’s genetic profile and their response to SSRIs.

Bernard Carroll at the Pacific Behavioral Research Foundation in Carmel, California, US, and colleagues carried out a study of 241 Korean patients with depression. The group found that people with two copies of a specific gene mutation had more than an 80% likelihood of responding to a class of antidepressants known as norepinephrine reuptake inhibitors (NRIs). But they were less than 60% likely to respond to SSRIs. Patients with only one copy of the gene mutation were only 39% likely to respond to NRIs.

“If we can get the cost of these tests down it will help physicians to prescribe the drug most likely to work first,” says Westley Clark director of the Center for Substance Abuse Treatment in Rockville, Maryland, US. Failed treatment attempts can increase patients’ sense of hopelessness and frustration, sometimes exacerbating their depression, Clark adds.

Journal reference: Science (DOI: 10.1126/science.1129663), Journal of the American Medical Association (vol 296, p 1609)

Source: NewScientist.com news service, 05 October 2006

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