April 22, 2001 (Dana Point, Calif.) -- Antidepressants can make it easier to quit smoking -- but at least one of these drugs doesn't work in people who carry a gene linked to addictive behavior.

The finding, reported here at the American Cancer Society's 2001 Science Writers Seminar, isn't all bad news. For one thing, it gives researchers a clear target to shoot for. "If we can show that a person's genetics plays a role in smoking behavior, we can develop drugs tailor-made for such people," says Paul M. Cinciripini, PhD, director of the tobacco research and treatment program at the University of Texas M.D. Anderson Cancer Center in Houston. Cinciripini and co-workers put 134 heavy smokers through an intensive stop-smoking treatment that used a combination of counseling and nicotine patches. Half the would-be quitters also got Effexor, an antidepressant medication, while the other half got sugar pills. Like other researchers, Cinciripini's team found that the antidepressant drug made it easier to quit. But unlike the others, they found out why. The mostly white, married men and women in the trial had also undergone tests for a gene linked to addictive behaviors such as drug use, pathological gambling, and smoking. The gene, known as DRD2, determines the makeup of a part of the brain that responds to a particular brain chemical -- dopamine. DRD2 comes in two types: A1 or A2. Since people get one copy from each parent, all people are pure A1/A1, pure A2/A2, or an A1/A2 mixture. People who had the pure A2/A2 gene type got a lot of help from the antidepressant drug. While struggling with quitting cigarettes, they didn't feel as bad as people who didn't get the drug. But people with even a single copy of the A1 gene didn't get any help from the antidepressant. They felt just as bad as people who didn't get the drug. "A fourth of the white U.S. population has the A1 [gene] -- but nearly 50% of current smokers have it," Cinciripini says. "But people don't have a smoker's gene. Not everybody who has the gene is destined to be a smoker. The environment, other genes, and behavior play major roles." So what can you say to a smoker who has the A1 gene? Tobacco-control expert David M. Burns, MD, has a suggestion. "What do you do with a kid who comes home with a bad grade in spelling? You don't say he never will learn to read and just give up on him -- you give him a little extra help," says Burns, a professor of medicine at the University of California, San Diego. "That is what we are trying to do by identifying people who may have more trouble when they are trying to quit."

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