University of Toronto. Canada: Researchers from University of Toronto and the University of
Pennsylvania can tell whether smokers will fare better with nicotine
patch or varenicline pill.
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.