Smokers' nicotine metabolism determines best way to quit

The effectiveness of a nicotine patch or pills in helping smokers quit may depend on how quickly they metabolise the nicotine in their body after kicking the habit, a new study has found.

In a first-of-its-kind randomised clinical trial, researchers found that 'normal' metabolisers of nicotine were significantly more likely to stay quit with the help of the drug varenicline compared to the nicotine patch at the end of treatment and 6-months later.

"Slow" metabolisers, on the other hand, would most likely benefit from the nicotine patch.

Varenicline (Chantix, manufactured by Pfizer) was just as effective as a nicotine patch at helping those people quit, but there were more overall side effects reported with the drug.

"Matching a treatment choice based on the rate at which smokers metabolise nicotine could be a viable strategy to help guide choices for smokers and ultimately improve quit rates," said lead author Caryn Lerman, a professor of Psychiatry and director of the Center for Interdisciplinary Research on Nicotine Addiction at Penn's School of Medicine.

The difference between slow and normal metabolisers is how long nicotine stays in the body after quitting. Nicotine levels drop more quickly in normal metabolisers, putting them at risk to succumb to the cravings and relapse.

But they are also more likely to be helped by medications like varenicline, which can increase levels of the "feel-good" hormone dopamine in their bodies and reduce cravings.

In the multi-center clinical trial, treatment-seeking smokers (1,246 in total) were categorised as either slow metabolisers (662) or normal metabolisers (584) and randomised to 11-weeks of either the nicotine patch (plus a placebo pill), varenicline (plus placebo patch), or a placebo pill and patch.

All received behavioural counselling, as well.

Participants were blood tested within seven days of beginning treatment to assess their nicotine metabolite ratio. To distinguish between slow or normal, the researchers looked at the ratio of two metabolites derived from nicotine during smoking, 3'hydroxycotine/cotine.

That ratio reflects the activity of the liver enzyme CYP2A6, the major nicotine and cotinine-metabolising enzyme that helps people metabolise nicotine more quickly.

At the end of treatment (week 11), participants' smoking behaviour was accessed to determine abstinence in both groups.

Researchers also followed up with participants at six and 12 months. Nearly 40 per cent of normal metabolisers on varenicline were still abstaining from smoking at the end of treatment compared to 22 per cent on the patch.

The findings indicated that varenicline was more efficacious than the nicotine patch for normal metabolisers, while the efficacy was equivalent for slow metabolisers.

However, this group reported more overall side effects, suggesting those smokers would gain more benefit from the patch.

The research is published in the journal Lancet Respiratory Medicine.