ESTES PARK, COLO. – Three major drug classes with diverse mechanisms of action are now approved for smoking cessation, providing an unprecedented array of options in terms of sequential and combination therapies.
Trying different agents, recycling them, combining them, and providing more intensive behavioral support are all important strategies, Dr. Allan Prochazka said at a conference on internal medicine sponsored by the University of Colorado.
Combination drug therapy is usually more effective than monotherapy, particularly for more heavily tobacco-dependent patients, Dr. Prochazka said. His go-to combinations are nicotine replacement therapy (NRT) plus bupropion (Zyban), or high-dose NRT using a nicotine patch plus nicotine gum or lozenges.
There is a definite need for more studies aimed at defining the optimal drug combinations, according to Dr. Pro-chazka, professor of medicine at the university and acting associate chief of staff at the Denver VA Medical Center.
The third class of drugs approved by the Food and Drug Administration for smoking cessation, in addition to NRT and the antidepressant bupropion, is varenicline (Chantix), a nicotine receptor partial agonist and the first designer drug for tobacco dependence.
A Cochrane Review of the pivotal clinical trials leading to varenicline's 2006 marketing approval concluded it had a 52% better quit rate than did long-acting bupropion, and there was a suggestion of moderately greater efficacy than NRT, although there were few trials comparing the two (Cochrane Database Syst. Rev. 2008; doi:10.1002/14651858.CD006103.pub3
And varenicline has a relatively low discontinuation rate. But because of varenicline's psychiatric morbidity and hefty price, Dr. Prochazka reserves it as second-line therapy in patients who have failed NRT and bupropion.
The VA smoking cessation guidelines also categorize varenicline as second-line therapy.
In July, the FDA ordered a black box warning for both varenicline and bupropion, urging prescribers to watch for the development of hostility, agitation, depression, and suicidality. The VA guidelines now call for varenicline to be avoided in psychiatric patients unless the smoking cessation intervention is done in collaboration with a mental health professional. For the time being, the best approach to smoking cessation in psychiatric patients remains unclear, Dr. Prochazka said.
In a generally healthy population of smokers, however, all three FDA-approved types of medication are safe and effective, he stressed. Nearly all smokers–even those who don't meet formal diagnostic criteria for tobacco dependence–will benefit from drug treatment along with brief counseling to quit the habit, he added.
Dr. Prochazka cited a clinical trial of triple combination treatment with bupropion, an NRT patch, and a nicotine inhaler that produced a 35% quit rate at 26 weeks, compared with 19% for the patch alone.
Side effects of the combination therapy were acceptable. There was less weight gain with triple therapy than with the patch alone (Ann. Intern. Med. 2009;150:447-54).
Varenicline has been combined with bupropion in a 38-patient, open-label, phase II trial. The result was a 58% cessation rate at 6 months (Nicotine Tob. Res. 2009;11:234-9).
Varenicline costs about $370 for 12 weeks' worth of 1-mg tablets, a price similar to 3 months' worth of Marlboro cigarettes, the general internist noted. In contrast, 3 months of generic long-acting bupropion runs $210.
Transdermal nicotine costs $70-$100 per month; nicotine gum retails for $35-$50 for 108 pieces, with most patients using 5-8 pieces daily; and nicotine inhaler cartridges cost up to $160 for a 2- to 4- week supply. Nicotine lozenges run $30-$40 for a box of 72; the maximum dose is 20 per day. And nasal nicotine spray costs about $47 per 100 doses, with the typical patient using 3-6 doses per day.
The Agency for Healthcare Research and Quality smoking cessation guidelines are an excellent resource, according Dr. Prochazka.
“It's probably the most evidence-based guideline in medicine,” he said.
The guidelines, updated in April 2008 (www.ahrq.gov/clinic/tobacco
▸ Ask all patients aged 18 and older at each visit about whether they smoke.
▸ Advise to quit in clear, strong, personalized language.
▸ Assess the smoker's willingness to try to quit now.
▸ Assist the quit attempt with medications, counseling, and other help.
▸ Arrange for follow-up.
A 10%-15% long-term quit rate is realistic for smokers in motivated primary care practices that use the AHRQ guidelines, Dr. Prochazka said.