Study Shows the Rate Smokers Metabolize Nicotine Predicts Best Method of Quitting

The success of different smoking cessation treatments could be predicted by how quickly smokers break down (metabolise) nicotine in their bodies, according to new research published in The Lancet Respiratory Medicine journal. The findings, from the largest pharmacogenetic [1] study of tobacco dependence treatment to date, reveal that normal metabolisers of nicotine have better quit rates with the non nicotine replacement therapy drug varenicline (trade name Chantix or Champix) compared with the nicotine patch, whereas slow metabolisers achieve similar quitting success using the nicotine patch but without the side-effects reported with varenicline.

“As many as 65% of smokers who try to quit relapse within the first week”*, explains Caryn Lerman co-lead author and a Professor of Psychiatry at the University of Pennsylvania in the USA. “Our findings show that matching a treatment based on the rate at which smokers metabolise nicotine could be a viable clinical strategy to help individual smokers choose the cessation method that will work best for them.”*

Every year, about 6 million people die of smoking-related diseases and an estimated US$200 billion is spent on tobacco-related health-care costs worldwide.

Smokers crave nicotine when their body’s nicotine levels drop. However, different people metabolise nicotine at different rates. Nicotine levels in the body drop more quickly in normal metabolisers (60% of smokers in the population) so they are more likely to smoke more and find it harder to quit. Previous research has identified a genetically informed biomarker of nicotine clearance–the nicotine metabolite ratio (NMR)–that reflects both environmental and genetic effects on nicotine metabolism. Until now, whether NMR status can be used to optimise treatment choice for individual smokers and improve outcomes has not been tested in a randomised trial.

In this study, Lerman and colleagues randomly assigned 1246 smokers who wanted to quit (662 slow metabolisers of nicotine and 584 normal metabolisers of nicotine) to 11 weeks of either the nicotine patch (plus a placebo pill), varenicline (plus placebo patch), or a placebo pill and patch. All participants also received behavioural counselling and were followed for 12 months after their quit date.

At the end of treatment (11 weeks), normal metabolisers taking varenicline were about twice as likely not to smoke as those using the nicotine patch, and were significantly more likely to still be abstaining from smoking 6 months later. Although varenicline was just as effective as nicotine patches at helping slow metabolisers to quit they reported more overall side-effects with the drug.

According to Dr Rachel Tyndale, co-lead author and Head of Pharmacogenetics at the Centre for Addiction and Mental Health at the University of Toronto, Canada, “To optimise quit rates for all smokers whilst minimising side effects, our data suggest treating normal metabolisers with varenicline and slow metabolisers with the nicotine patch. What is more, it is feasible that a point-of-care blood test to measure the rate at which nicotine is metabolised could be developed and implemented in clinical practice.”*

Writing in a linked Comment, Jennifer Ware, Neil Davies, and Marcus Munafò from the University of Bristol in the UK say, “The results reported by Lerman and colleagues are an important scientific advance. Should the findings be replicated, they might lead to changes in clinical practice through the implementation of prescriptions stratified on the basis of a biomarker test…[However] the extent to which tailoring treatment by a biomarker such as NMR is a cost-effective approach will depend on doing a full health economic assessment, including consideration of the relevant national context…which will also have to consider the effect of warnings stipulated by national regulatory bodies on prescribing rates of varenicline.”