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Depression (Unipolar) - Patient's Genes May Guide Antidepressant Use
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Patient's Genes May Guide Antidepressant Use
(HealthDay News)
by By Amanda Gardner
HealthDay Reporter
Updated: Oct 3rd 2006

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TUESDAY, Oct. 3 (HealthDay News) -- New insights into how genes affect an individual's response to particular drugs could someday speed the effective treatment of depression, researchers say.

Reporting in the Oct. 4 issue of the Journal of the American Medical Association, scientists say variations in a serotonin transport gene accurately predicted which patients would respond to selective serotonin reuptake inhibitor (SSRI) drugs such as Prozac.

They also identified key variations in the norepinephrine transporter (NET) gene. Those variants predicted response to nortriptyline, an antidepressant in a class of drugs called norepinephrine reuptake inhibitors (NRIs).

"I don't think this is going to change the way we treat depression, but it's another piece of the puzzle that will help us individualize treatment," said Dr. Julio Licinio, chairman of psychiatry at the University of Miami Miller School of Medicine. He was not involved in the research.

The study, conducted by researchers in the United States and Korea, shows "that it's important to look at gene variants in terms of treatment response," Licinio said.

Some 30 percent to 40 percent of patients fail their first drug treatment for major depression. Experts say that, right now, it's not possible to predict with any degree of accuracy which drug will work best for each patient.

Clinicians are pinning future hopes on "pharmacogenetics," or genetic factors that influence an individual's response to drugs.

There's reason for some optimism. Previous studies have shown that polymorphisms (individual differences in the DNA sequence) in the serotonin transporter gene might predict response to SSRIs, which include drugs such as Celexa, Paxil, Prozac and Zoloft.

Ethnic variations may also play a role. Prior studies have shown that gene variants linked to poor response to SSRIs among white patients were actually associated with a good response in Japanese and Korean patients.

"This raises some basic genetic questions about what exactly is the signal coming from the polymorphisms as to function and as to interaction with the drugs," Bernard Carroll, co-author of the research and scientific director of the Pacific Behavioral Research Foundation in Carmel, Calif., said in a prepared statement. "And it serves as a caution that results found in one ethnic group can't necessarily be transposed straight across to another ethnic group."

The new research was conducted at Samsung Medical Center in Seoul and was supported by the South Korean Ministry of Health and Welfare.

The study authors tracked the outcomes of a group of 241 Koreans diagnosed with major depression that had begun, on average, in the individuals' early-to-mid 50s.

The researchers were interested in two different types of antidepressants and associated pathways in the body: SSRIs and the serotonin transporter gene, as well as NRIs and the associated norepinephrine transporter (NET) gene.

Participants were treated for six weeks with an SSRI (either Prozac or Zoloft) or the NRI nortriptyline (brand names Aventyl or Pamelor).

Individuals who carried the "GG" polymorphism of NET had a better rate of response to NRI treatment than to SSRI treatment (83.3 percent and 58.7 percent, respectively).

"That's a 25 percent difference in response rate, so that is going to have a major impact, we would predict, on clinical practice," Carroll said.

The research also confirmed that response to SSRIs was associated with a genetic variation in the serotonin transporter gene.

Although the findings are preliminary and need to be replicated, particularly in a white population, "we're certainly optimistic that it's going to stand up," Carroll said.

More than half (56 percent) of Koreans and about 45 percent of whites have the GG polymorphism, the researchers noted.

"This is likely to still be a major finding in [whites] if the replications studies hold up," Carroll said. "If our findings are confirmed and if this genotyping is taken up in clinical services, then the market for SSRI drugs as first-line treatment will fall by around 50 percent. Another implication is that new drug development will shift to dual-action agents."

"The word is now out that depression is a very serious disorder with major public health and economic consequences," he continued. "There is a great deal of motivation on the professional side to do a better job of treating depression and this genetic prediction is an obvious place to start."

More information

For more on depression, visit the U.S. National Institute of Mental Health.