title: A double-blind randomized placebo-controlled pilot study of neuropsychiatric adverse events in abstinent smokers treated with varenicline or placebo.
abstract: BACKGROUND
  Varenicline is an α4β2 partial nicotinic agonist approved for smoking cessation. There have been spontaneous postmarketing reports of neuropsychiatric adverse events (NPAEs) in smokers without a history of psychiatric illness quitting with varenicline.
  
  
  METHODS
  One hundred ten smokers without history of psychiatric illness (screened by Structured Clinical Interview for DSM-IV) were randomized to 12 weeks of varenicline 1 mg twice daily (n = 55) or placebo. Adverse events were solicited systematically. Depressive symptoms, anxiety, aggression, and irritability were measured at baseline and weekly using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Hamilton Anxiety Scale (HAM-A), and the Overt Aggression Scale-Modified (OAS-M). The Profile of Mood States (POMS) was administered daily. Mixed-model analysis of repeated measures was conducted to compare mean changes in scores between groups across study periods.
  
  
  RESULTS
  Participants' mean baseline characteristics were 33 years of age, 22 cigarettes/day and Fagerström Test for Nicotine Dependence score > 7. Reported NPAEs were similar between groups. No suicidal events were reported. There were no significant differences between groups for the MADRS (treatment difference vs. placebo = .03, 95% confidence interval [CI] -.68-.73; NS), HAM-A (treatment difference [TD] = .14, 95% CI -.62-.90; NS), OAS-M Aggression subscale (TD = .5, 95% CI -1.18-2.18; NS), OAS-M Irritability subscale (TD = .08, 95% CI -.17-.34; NS), and the POMS total scores (TD = .5, 95% CI -.52-1.53; NS).
  
  
  CONCLUSIONS
  There were no significant differences between groups on measures of depressive symptoms, anxiety, or aggression/hostility. Systematically solicited NPAEs were similar between the varenicline and placebo groups.
authors.affiliation: Pfizer Pharmaceuticals Inc., New York, New York 10017, USA. dahlia.garza@pfizer.com
authors.forename: Dahlia
authors.initials: D
authors.lastname: Garza
authors.forename: Michael
authors.initials: M
authors.lastname: Murphy
authors.forename: Li-Jung
authors.initials: LJ
authors.lastname: Tseng
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Riordan
authors.forename: Anjan
authors.initials: A
authors.lastname: Chatterjee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000374:Aggression / Q000187:drug effects; D001007:Anxiety / Q000139:chemically induced; D001552:Benzazepines / Q000009:adverse effects* / Q000627:therapeutic use; D003863:Depression / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D011810:Quinoxalines / Q000009:adverse effects* / Q000627:therapeutic use; D012907:Smoking / Q000188:drug therapy*; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000188:drug therapy*; D016896:Treatment Outcome; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D000068580:Varenicline