Increasing the Dose of Varenicline in Patients Who Do Not Respond to the Standard Dose

Varenicline is a partial agonist of α4β2 nicotinic acetylcholine receptors. It is effective at dosages of 2 mg/d for 12 weeks, but not for all smokers. It is possible that increasing the dose can increase the drug efficacy. We reviewed the clinical records of consecutive smokers who had been treated in 2 smoking cessation services with varenicline at doses of 3 mg/d. In all cases, the treatment program consisted of a combination of behavioral therapy and drug treatment. Varenicline was prescribed at a standard dosage for 8 weeks. After 8 weeks of treatment, the dose was increased to 3 mg/d if patients tolerated varenicline well and continued smoking or, in spite of not smoking, if they experienced severe withdrawal symptoms. The sample included 73 patients, of whom 52 continued to smoke at 8 weeks and 21 stopped smoking but reported severe withdrawal discomfort. Carbon monoxide-validated continuous abstinence rates from week 9 to week 24 were 40% and 48% in these 2 subgroups, respectively. The increase in dosage was associated with adverse events in 22 patients (30%). These were mostly mild and included nausea, vomiting, abnormal dreams, and insomnia. Only 2 patients discontinued treatment (both because of nausea and vomiting). Thus, we conclude that increasing the varenicline dose in smokers who do not respond to the standard dose after 8 weeks of treatment is associated with limited adverse events and high success rates.