Quitting smoking? Read this first

If you’re trying to quit smoking, new research from the University of Toronto suggests the first thing you need to understand is your DNA. 

“In this new trial, we’ve shown that it is possible to optimize quit rates for smokers, while minimizing side effects, by selecting treatment based on whether people break down nicotine slowly or normally,” said Dr. Rachel Tyndale, a professor of pharmacology & toxicology and psychiatry at U of T and a senior scientist at the Centre for Addiction and Mental Health’s Campbell Family Mental Health Research Institute. 

Tyndale was the co-lead on the study published recently online in The Lancet Respiratory Medicine. The randomized clinical trial, the first of its kind, was performed in collaboration with researchers from the University of Pennsylvania. The clinical portion of the study was undertaken at CAMH and led by Dr. Tony George, professor of psychiatry and clinical director of the schizophrenia program at CAMH. The research is already garnering headlines around the world: read the CBC story; read the International Business Times article; read the Huffington Post story; read the BBC coverage; read the New York Daily News story.)

At issue is how long nicotine stays in the body between cigarettes and after users stop smoking. In normal metabolizers, nicotine levels drop more quickly, putting them at risk of succumbing to cravings and relapse. Researchers said normal metabolizers are more likely to be helped by medications such as varenicline – known by the brand name Champix – which can increase levels of the “feel-good” hormone dopamine and reduce cravings.

Normal metabolizers of nicotine were significantly more likely to remain abstinent from smoking after treatment with varenicline compared to the nicotine patch, at the end of treatment and six months later. Slow metabolizers, on the other hand, could benefit the most from the nicotine patch, the authors suggest. Varenicline was just as effective as the patch for “slow” metabolizers, but it led to more side effects than the patch.

“This is a much-needed, genetically-informed biomarker that could be translated into clinical practice,” said co-lead Dr. Caryn Lerman, professor of psychiatry and director of the Center for Interdisciplinary Research on Nicotine Addiction at the University of Pennsylvania. “Matching a treatment choice based on the rate at which smokers metabolize nicotine could be a viable strategy to help guide choices for smokers and ultimately improve quit rates.”  

Unfortunately, there are no commercial tests for this biomarker on the market – so, right now, smokers and their physicians currently have no way of knowing which approach is likely to work best. Tyndale said she hopes the research findings will spur others to create such a test. Such a test could be used by doctors to optimize the cessation rates for all people without unnecessarily exposing people to a drug which doesn’t work as well, or has avoidable side effects, she said. 

In the clinical trial, 1,246 smokers seeking treatment were categorized as either slow metabolizers (662) or normal metabolizers (584). They were randomized to receive one of the following for 11 weeks: the nicotine patch plus a placebo pill; varenicline plus placebo patch; or both placebo pill and patch. All received behavioural counselling. The trial was conducted at four academic medical centres

Participants’ status as either a normal or slow metabolizer was based on a measure called the nicotine metabolite ratio (NMR). NMR is the ratio of two chemical products of nicotine, which break down at different rates based on different genetic versions of CYP2A6, a liver enzyme. Participants’ smoking behaviour was assessed at the end of treatment, and six and 12 months later. 

Among normal metabolizers, nearly 40 per cent taking varenicline were still abstaining from smoking at the end of treatment, compared to 22 per cent on the nicotine patch. The quit rates, as expected based on the difficulty of prolonged quitting success, decreased at six and 12 months, but the overall pattern of response for both normal and slow metabolizers on the patch and varenicline remained.

Smoking rates in North America have fallen substantially since the 1960s, but nearly 1.8 million Ontario adults and students still report smoking, according to recent CAMH surveys. Worldwide, about six million people die every year from smoking-related diseases, and $200 billion is spent on tobacco-related health care costs.  

Michael Kennedy writes about health for U of T News.