A genetic variation that impacts how quickly smokers process nicotine can help predict whether those who try to quit are likely to respond to nicotine replacement therapy, according to a new study published in the journal Addiction.
The gene, however, has very little effect on the success of treatment with the drug buproprion (Zyban), an antidepressant that is often prescribed help people quit smoking by reducing their cravings and other withdrawal effects.
“Smokers often struggle with cravings and withdrawal when stopping smoking.” said lead researcher Laura Jean Bierut, M.D., professor of psychiatry.
“This study gives us insights into who may respond to different types of smoking cessation medications so that we can improve the odds of quitting.”
“Clinically, we often observe that responses to medication vary from one patient to another,” said first author Li-Shiun Chen, M.D., assistant professor of psychiatry. “To understand those differences, we studied a gene called CYP2A6, which controls nicotine metabolism in our bodies.
“It turns out that most of us metabolize nicotine rapidly, but others can metabolize it much more slowly.”
Earlier research has shown that roughly 70 percent of individuals have a variation of the CYP2A6 gene that helps them metabolize nicotine quickly, while 30 percent metabolize nicotine more slowly.
“Nicotine levels drop more quickly in fast metabolizers after they quit smoking,” Chen said.
“In slow metabolizers, nicotine stays in the body longer. We have found that fast metabolizers of nicotine are more likely to relapse when they try to quit because when their nicotine levels drop rapidly, they can fall victim to cravings, but they’re also more likely to be helped by nicotine replacement therapy, which can increase nicotine levels and help control those cravings.”
For the study, the researchers evaluated more than 700 smokers, who were at least 18 years old, smoked 10 or more cigarettes per day, were of European ancestry and wanted to quit smoking.
Through eight weeks of smoking cessation therapy, participants received six 10-minute counseling sessions to help them quit. Some also received buproprion or nicotine replacement therapy with nicotine patches and/or lozenges. Another group was given both buproprion and nicotine replacement, and the rest were given inactive placebos.
The findings showed that one in three fast metabolizers responded to nicotine replacement therapy. Among slow metabolizers, the response rate was only one in 1,000.
Furthermore, the researchers found that the CYP2A6 gene could not predict whether a smoker would respond to treatment with the drug buproprion.
“Individual genetic analysis is becoming more and more common, and the cost is getting lower all the time,” Chen said. “I think eventually we will be able to locate these gene variants quickly and inexpensively so that we can tailor treatments to individuals so they can avoid therapies that probably won’t help them very much.”
About seven in 10 former smokers start smoking again within three months of quitting. At the one-year mark, this number is close to nine in 10, even with the help of medication.
The study was conducted by researchers at Washington University School of Medicine in St. Louis, the University of Wisconsin School of Medicine and the University of Minnesota.