title: Adverse Effects Cause Varenicline Discontinuation: A Meta-Analysis.
abstract: OBJECTIVE
  Varenicline, the newest agent marketed for smoking cessation is regarded as effective in providing prolonged smoking abstinence. However, its adverse effect profile may cause discontinuation, potentially reducing smoking abstinence rates, thus requiring an examination of the frequency and impact of adverse effects on discontinuation.
  
  
  METHODS
  We sought only Randomised Controlled Trials (RCTs) evaluating the effectiveness and safety of varenicline on humans, with a follow-up period of at least three months and an average Fagerstrom Test for Nicotine Dependence (FTND) score at least 5 (moderate dependence) for both the active and placebo groups. PubMed, Medscape, JCU One Search, ClinicalTrials.gov (U.S.), and the Cochrane Collaboration from January 2006 to January 2015 were searched. Fixed and random effects models were run to determine relationships between adverse effects and premature discontinuation from varenicline.
  
  
  RESULTS
  12 RCTs were included, involving 5 459 patients, with those receiving varenicline found to be nearly twice as likely (Odds ratio (OR) = 1.82 [1.47; 2.26]) to experience adverse effects compared to those patients on a placebo. The active group experienced nearly a 1.5 times higher (OR = 1.47 [1.19; 1.81]) rate of discontinuation. Nausea, insomnia, and headache are the most commonly reported adverse effects, with ORs of 4.40 [3.80; 5.11], 1.75 [1.48; 2.08], and 1.20 [1.02; 1.41] respectively.
  
  
  CONCLUSIONS
  Adverse effects experienced during varenicline treatment appear to be associated with higher discontinuation, which are linked to lowered smoking cessation rates, suggesting a need for strategies to minimise the impacts of adverse effects, to better ensure adherence.
authors.affiliation: Room 031, Building 47, James Cook University, Townsville, 4811, Australia. aaron.drovandi@jcu.edu.au.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Drovandi
authors.forename: Carla C
authors.initials: CC
authors.lastname: Chen
authors.forename: Beverley D
authors.initials: BD
authors.lastname: Glass
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D055118:Medication Adherence; D018722:Nicotinic Agonists / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012907:Smoking / Q000188:drug therapy* / Q000453:epidemiology; D016540:Smoking Cessation / Q000379:methods*; D000068580:Varenicline / Q000009:adverse effects*
chemical_list: D018722:Nicotinic Agonists; D000068580:Varenicline