smoking and varenicline

there were a few important articles in the jan 8th JAMA on smoking -- i will highlight 2 of them on varenicline, a partial agonist which binds with high affinity as well as specificity to neuronal acetylcholine receptors. smoking cessation in smokers is the most significant single intervention to decrease mortality, and 62% of deaths in female smokers/60% of deaths in male smokers are attributable to smoking.

1. i had sent out a general smoking cessation article about one year ago from JAMA which referenced some small study finding benefit of combining varenicline with bupropion. the current study (see smoking varenicline and buprop jama 2014 in the dropbox, or doi:10.1001/jama.2013.283185) was a 12-month multi-center RCT comparing varenicline with bupropion vs varenicline with placebo, with both medications dosed as is generally recommended.  results:

    --500 patients (mean age 42, 94% white, 45% women, 78% completed at least some college -- study done at Mayo clinic and univ minnesota), though only 62% completed the study (dropout rates similar in both groups)
    --of those completing study:
        --at 12 weeks: 53% in combo group achieved smoking abstinence and 56% 7-day point-prevalence smoking abstinence (ie, self-reported tobacco cessation for previous 7 days, confirmed by carbon monoxide level), vs 43% and 49% with varenicline alone
        --at 26 weeks: 37% with prolonged and 38% with 7-day point prevalence abstinence in combo and 28% and 32% with varenicline alone
        --at 52 weeks:31% with prolonged and 37% with 7-day point prevalence abstinence in combo and 25% and 29% with varenicline alone
    --adverse effects: combo with more anxiety (7% vs 3%) and depressive sx (4% vs 1%) -- a bit surprising since the combo group had bupropion, a pretty potent anti-depressant....
    --of the above, the only findings reaching statistical significance were: smoking abstinence at 12 and 26 weeks. no significance at 52 weeks, or any of the measures of 7-day point prevalence.
    --subgroup analysis: for heavy smokers (>20 cigs/day), combo therapy assoc with statistically significant prolonged smoking abstinence at 12 weeks (50% vs 36%), 26 weeks (35% vs 19%) and 52 weeks (32% vs 17%), with similar numbers for those with high levels of nicotine dependence.
    --less weight gain in combo group than in varenicline alone (1.1 vs 2.5kg at 12 weeks, 3.4 vs 3.8kg at 26 weeks, and 4.9 vs 6.1kg at 52 weeks)

this trial confirms the concept of combination therapy and extends it to varenicline plus bupropion. other studies have found improved abstinence rates with combo of bupropion and nicotine replacement therapy (NRT), and with using combo NRTs (eg patch for maintenance nicotine levels, with inhaler or lozenge for times of increased urge to smoke).  this study, though small numbers of patients and pretty high dropout rate, does suggest that the combo of bupropion and varenicline is effective, esp in those who are heavy smokers.

there are minimal studies of electronic cigarettes, as per a prior email/blog. mostly short-term (eg 12 weeks: 14% abstinence with e-cigarettes vs 4% with nicotine-free device; another study for 6 months found no statistical difference between e-cigarettes, nicotine patch or placebo). of note, the FDA has found important carcinogenic contaminants in 2 brands of e-cigarettes: polycyclic aromatic hydrocarbons and nitrosamines. (though my experience in a relatively small number of smokers is that the e-cigs did help them quit, and cigarettes have many more dangerous additives)


2. the above study excluded patients with major medical or psych illnesses, and there is concern that varenicline could exacerbate psych problems. in addition, the baseline smoking rates are significantly higher in people with mental illness (25% vs 19%, in 2011). not surprisingly, those with mental illness who received mental health treatment quit smoking at a higher rate than those who did not receive treatment (37% vs 33%). another JAMA article looked at patients with schizophrenia or bipolar disease who had quit smoking on varenicline and then were put on maintenance of varenicline plus cognitive behavioral therapy (CBT) vs CBT alone (see varenicline schiz jama 2014 in the dropbox, or doi:10.1001/jama.2013.285113), as follows:

    --of 203 smokers (60% smoking more than 20 cigs/d) with medically-treated and stable schizophrenia or bipolar dz, then treated with varenicline in a 12-week open trial, 87 had at least 14 days of continuous abstinence by the end of this period (88% had schizophrenia, 12% bipolar)
    --these 87 abstinent patients were randomized to continued varenicline to complete 52 weeks, along with tapering CBT sessions (median of 26 sessions), vs  placebo and CBT (24 sessions)
    --at the end of the varenicline intervention (52 weeks), point prevalence abstinence rate of 60% with varenicline vs 19% placebo
    --at the end of the study (76 weeks -- ie, 24 weeks after stopping intervention), abstinence rates of 30% vs 11% (pretty impressive!!)
    --and, perhaps most noteworthy, no difference in adverse events with varenicline in the open-label part of the study, and there were actually fewer reports of agitation or excitement with the maintenance varenicline than placebo (though more headaches)

so, small study, but does suggest that we can use varenicline in patients with schizophrenia or bipolar disease, which i think many of us were wary about.