Randomized Clinical Trial Comparing a Medication, i.e., Sustained-Release Bupropion (Zyban®) With an Ultrashort (1 1/2 d) Manual-Based Psychotherapeutic Intervention, Psychodynamic Model Training®

Study design

This randomized clinical trial was designed to compare the efficacy and safety of a manual-based 1.5-day psychotherapeutic intervention, i.e., Psychodynamic Model Training®, with a medication, i.e., sustained-release bupropion (Zyban®), as smoking cessation aids. In order to render the data comparable to previously obtained bupropion data, the bupropion treatment regimen and study protocol closely followed that by Jorenby et al. 1999.(3) As an improvement over previous protocols(3-5), nonsmoking status was verified not only by determination of exhaled carbon monoxide (CO) levels but also by tandem mass spectrometric (LC/MS/MS) analysis of urine cotinine(6;7), a marker of higher sensitivity than CO.(8)

Subjects, screening, inclusion and exclusion criteria, and randomization

Female and male smokers were recruited between July 2005 and December 2005 by announcements in the local media (press, local radio stations) and in the newsletter (http://www.stgkk.at/mediaDB/104832.PDF) of the governmental Styrian Regional Health Care System (Steiermaerkische Gebietskrankenkasse, STGKK), the sponsor of the present study. Interested smokers were first screened by telephone interview and then scheduled for the study intake interview. The first subject was enrolled in July 2005, and follow-up was completed in January 2007. Of a total of 951 persons screened, 790 met the screening criteria and were enrolled and randomized to one of two treatments according to a randomization list in the care of the steering committee at the Medical University Innsbruck. Great care was taken to preserve treatment allocation concealment: Only after the subject had given his/her written consent, a sealed envelope containing the treatment allocation was broken by the interviewer and presented to the subject. The study protocol was registered with the European Medicines Agency (emea.europa.eu; EudraCT-Nr. 2005-006189-32) and was approved by the local governmental review board. The study was conducted in compliance with the ethical principles of the Declaration of Helsinki (www.wma.net/e/policy/b3.html ; accessibility verified May 16, 2007) and the standards on good clinical practice developed by the International Conference on Harmonization (www.ich.org/cache/compo/276-254-1.html ; accessibility verified May 16, 2007.)

Inclusion criteria were an age of at least 18 years, a cigarette consumption of at least 15 cigarettes per day in the last 3 months, and the willingness to contribute EUR 70 to the treatment costs, regardless of the treatment modality. Exclusion criteria, as assessed by the study-site physicians, were any psychiatric diagnosis except nicotine or caffeine dependence, any current psychopharmacological treatment, known hypersensitivity to bupropion, epilepsy, liver cirrhosis, brain tumor, pregnancy (verified by an immunological test at the intake interview and 3 weeks after the first day of the first menses occurring within treatment), lactation, any serious or unstable cardiac, renal, hypertensive, pulmonary, endocrine, or neurologic disorder, ulcers, dermatologic disorders, current use of other smoking cessation treatments, and regular use of any noncigarette tobacco product. After induction of the first 620 subjects, it became apparent that more subjects randomized to the bupropion group dropped out immediately after learning of their treatment allocation. To compensate for this higher rejecter rate in the bupropion group, the remaining 170 subjects were randomized to bupropion vs psychotherapy at a ratio of 2:1. Seven of the 420 subjects randomly allocated to the bupropion group and 4 of the 370 to the psychotherapy group were found to meet exclusion criteria by the study's physicians only after the randomization (bupropion: bulimia, 3 cases of major depression, 2 cases with antidepressant medication, anticoagulant medication; psychotherapy: 4 cases with a previously undisclosed psychiatric diagnosis) and had to be excluded before treatment started. Therefore, the final intention-to-treat (ITT) sample consisted of 413 subjects in the bupropion and 366 subjects in the psychotherapy group.