Williams 2012

Methods	Countries: Canada, USA Setting: 12 sites Aim: To evaluate primarily safety, but also efficacy of varenicline in smokers with schizophrenia or schizoaffective disorders Dates conducted: May 2008 ‐ April 2010 Study Design: Double‐blind placebo‐controlled RCT. Sample size [120] was considered sufficient to detect a between‐group difference in 7‐day PPA "for a medium effect size"
Participants	128 adults, diagnosed with stable schizophrenia or schizoaffective disorders, smoking at least 15 CPD and motivated to quit. Randomised to varenicline (85) or placebo (43). 77% men aged 18 ‐ 75
Interventions	1. Varenicline 1.0 mg x 2/d for 12 wks, including wk 1 at titrated dose 2. Placebo tablets as above. Weekly clinic visits, for safety and efficacy, ≤ 30‐min counselling sessions; after treatment phase, clinic visits at wks 13, 16, 20, 24, with brief phone calls at wks 14, 18 and 22. Follow‐up sessions included brief (≤ 10 mins) counselling. AEs collected to 30 days after treatment, and neuropsychiatric AEs to wk 24
Outcomes	Primary outcome: N of participants with adverse and serious adverse events from baseline to 30 days after end of treatment (12 wks). N of participants with psychiatric adverse events, including suicidal ideation or behaviour Secondary outcomes: CO‐confirmed PPA at wks 12 and 24; 50%+ reduction in CPD; change in CPD from baseline. Assessments on mood and psychiatric scales Validation was by exhaled CO ≤ 10 ppm Dropouts in treatment phase: 14 (varenicline), 3 (placebo); follow‐up phase: 10 (varenicline), 3 (placebo) 1 varenicline participant died during follow‐up phase
Treatment type	Medication: VARENICLINE
Notes	The study was funded by Pfizer New for 2012 update
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Subjects were randomized (2:1) to varenicline or placebo ... and were stratified according to antipsychotic medication type (typical vs atypical)."
Allocation concealment (selection bias)	Unclear risk	Not stated
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not yet reported