A PLACEBO-CONTROLLED STUDY OF 3 CLONIDINE DOSES FOR SMOKING CESSATION

Background and objective: Clonidine in doses of 150 to 450 mu g per da y has been reported to reduce symptoms of craving associated with toba cco withdrawal and, in some cases, to improve long-term abstinence rat es of smoking cessation programs. However, subjects frequently experie nced symptoms of dry mouth and drowsiness. This study investigated the lower end of the effective dose range of clonidine for smoking cessat ion to identify the lowest useful dose and thus minimize the adverse e ffects of the drug. Methods: A randomized, double-blind, four-way cros sover design compared the effects of clonidine doses or placebo within individual subjects for 4 consecutive weeks. Smokers who were highly nicotine dependent were randomly assigned to different sequences of pl acebo and 300, 200, and 100 mu g clonidine per day. Subjects were trea ted for 4 days of each treatment week and began smoking cessation from the end of day 2. Smokers recorded withdrawal symptoms on multiple vi sual analog scales during days 3 and 4 before resuming normal smoking until the next period of smoking cessation. Results: A statistically s ignificant dose-response effect was found for craving scores (dose-res ponse gradient, -3.8/100 mu g; 95% confidence interval [CI], -6.2 to - 1.5; p = 0.002) but not for pooled tobacco withdrawal scores. The dose of 300 mu g per day reduced mean craving scores significantly (-16%; 95% CI, -31% to -1%). Dosing with 200 mu g approached statistical sign ificance (-14% 95% CI -30% to 1%) but dosing with 100 mu g did not (-6 %; 95% CI, -22% to 9%). Troublesome adverse experiences were reported by more than 67% of subjects during 200 and 300 mu g dosing. Conclusio ns: This study showed a statistically significant dose-response effect of clonidine on tobacco withdrawal craving and a reduction in mean cr aving scores of 16% during 300 mu g dosing. However, its clinical usef ulness is doubtful because of frequently reported adverse experiences.