The agony of quitting smoking is all too familiar: a repeated cycle of determination and then dwindling resolve, peppered with trials of nicotine gum, patches, and even medication. Some people find success with drugs, such as bupropion (trade name Zyban), an antidepressant commonly prescribed for smoking cessation. But for others, counseling and other strategies seem much more useful than medication.
New research suggests that genetic testing could quickly distinguish which smokers would benefit from bupropion. The findings add to a growing number of studies linking genetics to nicotine addiction and the ability to quit, and raise the possibility that quitting strategies could be more effectively tailored to individual patients.
“It takes a lot for a smoker to prepare themselves to quit smoking,” says Rachel Tyndale, a scientist at the University of Toronto and one of the authors of the new pharmacogenetics study. “If we could identify the right approach in that time, I think it would improve quit rates.”
Bupropion–one of only two non-nicotine smoking-cessation drugs approved by the U.S. Food and Drug Administration–inhibits the rewarding effects of smoking. The drug is broken down by an enzyme called CYP2B6I, whose structure and function vary from individual to individual. In the new study, published this month in the journal Biological Psychiatry, scientists developed a genetic test to identify which of two variations of the enzyme an individual carried–either CYP2B6*6 or CYP2B6*1. They found that people with the CYP2B6*1 variation (about 55 percent of people of European descent) showed no added benefit in quitting smoking when given bupropion: about 30 percent of smokers quit regardless of whether they took the drug or a placebo. Most of the people in this group who successfully quit at the start of treatment were still not smoking six months later.
People with one or two copies of the CYP2B6*6 mutation had a harder time quitting smoking. (In fact, none of the people with two copies of the mutation–one from their mother and one from their father–could quit on placebo.) But this group also showed greater benefit from bupropion: those taking the drug were three times more likely to have stayed off cigarettes at six months than were those taking placebo.
“This is exactly what is needed in the clinical realm,” says Joni Rutter, a program director at the National Institute of Drug Abuse, in Bethesda, MD, which partly funded the study. She points out that in the general population, 80 to 90 percent of those who try to quit relapse within six months. “If we can figure out who will benefit from bupropion before we give it to them, it takes some of the guesswork out of treating the smoking population.”