title: Systematic review and meta-analysis of combination therapy for smoking cessation.
abstract: OBJECTIVE
  To review published clinical trials on combination therapy for smoking cessation and determine the role of this regimen for treating tobacco dependence.
  
  
  METHODS
  Search terms included in this systematic review were nicotine replacement patch, nicotine replacement therapy, nicotine replacement gum, nicotine replacement inhaler, nicotine replacement nasal spray, nicotine replacement lozenge, bupropion SR (for sustained release), combination therapy, smoking cessation, and varenicline. Trials conducted from 1994 through October 10, 2007, were identified using EBM Reviews: Cochrane Central Register of Controlled Trials and Medline.
  
  
  METHODS
  Clinical trials of various regimens for smoking cessation were included based on a large sample size (n > or = 200); use of first-line smoking cessation therapies; double-blind, randomized, placebo-controlled design; and study duration of 1 year or more. The primary objective of the included clinical trials was to assess the efficacy of combination therapy. Studies that involved medications other than first-line therapies, adolescents, and post hoc analyses and that were not written in English were excluded.
  
  
  RESULTS
  Five clinical trials meeting the inclusion criteria were reviewed. All of the studies included the use of the nicotine replacement patch along with one other agent. A total of 2,204 patients were treated. Combination therapy was significantly better than monotherapy at all pooled comparisons (P < 0.05). The aggregated relative risk of abstinence comparing combination with single treatment groups was 1.42 (95% CI 1.21-1.67), 1.54 (1.19-2.00), and 1.58 (1.25-1.99) at 3, 6, and 12 months, respectively. Adverse effects with combination nicotine replacement therapy were minimal and similar to placebo or monotherapy.
  
  
  CONCLUSIONS
  Current literature indicates that combination therapy is statistically better than monotherapy in smoking cessation treatment as assessed by 3-, 6-, and 12-month abstinence rates. Adverse effects and adherence to combination therapy are similar to monotherapy and placebo.
authors.affiliation: Harvard School of Public Health, Boston, MA, USA.
authors.forename: Sima D
authors.initials: SD
authors.lastname: Shah
authors.forename: Lori A
authors.initials: LA
authors.lastname: Wilken
authors.forename: Susan R
authors.initials: SR
authors.lastname: Winkler
authors.forename: Swu-Jane
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016642:Bupropion / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000188:drug therapy*; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D011810:Quinoxalines; D016642:Bupropion; D009538:Nicotine; D000068580:Varenicline