BACKGROUND AND OBJECTIVE:Clonidine in doses of 150 to 450 micrograms per day has been reported to reduce symptoms of craving associated with tobacco withdrawal and, in some cases, to improve long-term abstinence rates of smoking cessation programs. However, subjects frequently experienced symptoms of dry mouth and drowsiness. This study investigated the lower end of the effective dose range of clonidine for smoking cessation to identify the lowest useful dose and thus minimize the adverse effects of the drug. METHODS: A randomized, double-blind, four-way crossover 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 placebo and 300, 200, and 100 micrograms clonidine per day. Subjects were treated for 4 days of each treatment week and began smoking cessation from the end of day 2. Smokers recorded withdrawal symptoms on multiple visual analog scales during days 3 and 4 before resuming normal smoking until the next period of smoking cessation. RESULTS: A statistically significant dose-response effect was found for craving scores (dose-response gradient, -3.8/100 micrograms; 95% confidence interval [CI], -6.2 to -1.5; p = 0.002) but not for pooled tobacco withdrawal scores. The dose of 300 micrograms per day reduced mean craving scores significantly (-16%; 95% CI, -31% to -1%). Dosing with 200 micrograms approached statistical significance (-14%; 95% CI -30% to 1%) but dosing with 100 micrograms did not (-6%; 95% CI, -22% to 9%). Troublesome adverse experiences were reported by more than 67% of subjects during 200 and 300 micrograms dosing. CONCLUSIONS: This study showed a statistically significant dose-response effect of clonidine on tobacco withdrawal craving and a reduction in mean craving scores of 16% during 300 micrograms dosing. However, its clinical usefulness is doubtful because of frequently reported adverse experiences.
RCT Entities:
BACKGROUND AND OBJECTIVE:Clonidine in doses of 150 to 450 micrograms per day has been reported to reduce symptoms of craving associated with tobacco withdrawal and, in some cases, to improve long-term abstinence rates of smoking cessation programs. However, subjects frequently experienced symptoms of dry mouth and drowsiness. This study investigated the lower end of the effective dose range of clonidine for smoking cessation to identify the lowest useful dose and thus minimize the adverse effects of the drug. METHODS: A randomized, double-blind, four-way crossover 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 placebo and 300, 200, and 100 micrograms clonidine per day. Subjects were treated for 4 days of each treatment week and began smoking cessation from the end of day 2. Smokers recorded withdrawal symptoms on multiple visual analog scales during days 3 and 4 before resuming normal smoking until the next period of smoking cessation. RESULTS: A statistically significant dose-response effect was found for craving scores (dose-response gradient, -3.8/100 micrograms; 95% confidence interval [CI], -6.2 to -1.5; p = 0.002) but not for pooled tobacco withdrawal scores. The dose of 300 micrograms per day reduced mean craving scores significantly (-16%; 95% CI, -31% to -1%). Dosing with 200 micrograms approached statistical significance (-14%; 95% CI -30% to 1%) but dosing with 100 micrograms did not (-6%; 95% CI, -22% to 9%). Troublesome adverse experiences were reported by more than 67% of subjects during 200 and 300 micrograms dosing. CONCLUSIONS: This study showed a statistically significant dose-response effect of clonidine on tobacco withdrawal craving and a reduction in mean craving scores of 16% during 300 micrograms dosing. However, its clinical usefulness is doubtful because of frequently reported adverse experiences.