HIGH-DOSE NICOTINE PATCH THERAPY - PERCENTAGE OF REPLACEMENT AND SMOKING CESSATION

Objective.-To assess the level of nicotine replacement, evidence of ni cotine toxicity, and withdrawal symptom relief with placebo and 11-, 2 2-, and 44-mg/d doses of transdermal nicotine. A secondary objective w as to assess short- and long-term smoking cessation rates. Design.-Ran domized, double-blind, placebo-controlled inpatient/outpatient trial. Subjects.-Seventy-one cigarette smokers stratified according to light (n=23), moderate (n=24), and heavy (n=24) smoking rates. Interventions .-After baseline measures were obtained, subjects were randomly assign ed to placebo or an 11-, 22-, or 44-mg/d dose of transdermal nicotine and admitted to a special hospital unit for intensive inpatient treatm ent of nicotine dependence. During the 6-day inpatient stay, daily nic otine and cotinine levels were determined from trough and peak blood s amples. Outpatient patch therapy continued for 7 weeks following the h ospital stay, and those initially assigned to placebo were randomly as signed to 11 or 22 mg/d. At week 4, the dosage of those initially assi gned to 44 mg/d was reduced to 22 mg/d. Main Outcome Measures.-Percent age of replacement of cotinine was calculated by dividing the steady-s tate levels attained during patch therapy by the corresponding baselin e levels. Abstinence from smoking was verified by expired air carbon m onoxide. Withdrawal symptoms and nicotine toxicity were assessed daily through questionnaires during the inpatient stay. Follow-up visits we re at 3, 6, 9, and 12 months. Results.-There was a statistically signi ficant relationship between baseline smoking rate and baseline trough and peak blood cotinine levels (r(s)=0.39, r(s)=0.45; P<.001 in both i nstances). A dose-response relationship was observed with higher patch doses, which produced a higher percentage of cotinine replacement and better withdrawal symptom relief. Only one subject (a light smoker as signed to the 44-mg dose) developed signs of nicotine toxicity. There was a positive association between the week 2 patch dose and the bioch emically confirmed abstinence at the end of patch therapy (P=.007) but not for subsequent follow-up times, A higher percentage of cotinine r eplacement was associated with the higher 8-week smoking abstinence ra te (P=.03), an association not found at long-term follow-up. Conclusio n.-A 44-mg/d dose of nicotine patch therapy appears to be safe for use in heavy smokers. Cigarette smoking rates can be used to estimate the initial nicotine patch dose. Monitoring blood cotinine levels at base line and steady state can be used for assessing the adequacy of nicoti ne replacement. Withdrawal symptom relief can be improved with more co mplete nicotine replacement. Achieving a greater percentage of nicotin e replacement may increase the efficacy of nicotine patch therapy.