Commentary

What Matters – Higher-dose varenicline


 

Although some may perceive that cigarette smoking is the leading cause of statistics, smoking sadly remains the leading cause of preventable death and disability in the United States. Smoking causes one of every five deaths. Tobacco dependence is an addiction, and addiction is hard – really hard. That is why, despite mass casualties from a risk known to arguably all smokers, an estimated 45.3 million U.S. adults (19.3%) currently light up some days or every day.

Because there is no safe level of smoking, abstinence remains the goal. Varenicline, an alpha 4 beta 2 nicotine acetylcholine receptor partial agonist, is one of the most effective treatments we have ever had to combat tobacco dependence. Varenicline is given at a target dose of 1 mg twice per day by mouth. But, as most of us have realized, varenicline does not work for everybody.

New data suggest, however, that for patients who do not respond to the standard dose of varenicline, a higher dose may be helpful (Mayo Clin. Proc. 2013;88:1443-5).

Dr. Carlos A. Jiménez-Ruiz of Spain’s Smoking Cessation Service in the County of Madrid reviewed data from a clinical program consisting of behavioral and pharmacologic components. Patients received varenicline at a target dose of 1 mg twice a day for 8 weeks. After 8 weeks, if patients were still smoking or were smoking abstinent but experienced significant withdrawal, the dose was increased to 3 mg a day (1 mg every 8 hours).

Biochemically confirmed smoking abstinence from week 9 to week 24 was 40% in those who had continued smoking after 8 weeks and 48% in the group abstinent from smoking but experiencing significant withdrawal. In those two groups, 30% of patients had adverse events, which included nausea, vomiting, abnormal dreams, and insomnia.

Smokers receiving varenicline 3 mg per day in this study smoked an average of 36 cigarettes per day. The study authors hypothesized that a higher dose may be required for some smokers, because the standard dose does not saturate enough nicotinic receptors.

We do not know the extent to which this is true, but data suggest that higher doses of other medications, such as nicotine patches, are more effective for smokers than lower doses. Prescribing may work for some smokers, but the higher dose may generate a preauthorization. Let me know if it does.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. Dr. Ebbert has received research funding from Pfizer, manufacturer of varenicline. Contact him at imnews@frontlinemedcom.com.

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