Chengappa 2014

Methods	Country: Pittsburgh, USA Setting: 2 outpatient clinics, Western Psychiatric Institute and Clinic; and Dubois Medical Regional Center, Pennsylvania Aim: To assess the efficacy and safety of varenicline to assist in smoking cessation among patients with bipolar disorder who were euthymic and motivated to quit smoking Study Design: Double‐blind placebo‐controlled RCT Dates conducted: February 2010 ‐ March 2013 Analysis: Power calculation of 60 in each arm Randomised placebo‐controlled quadruple‐blind trial
Participants	60 outpatient smokers with DSMIV‐diagnosed bipolar disorder, aged 18 ‐ 65, stable state or on medication, willing to quit in the next 30 days, 10+ CPD; randomised to varenicline (31) or placebo (29) Mean age 46, 69% women, 66% white, mean CPD 18.1, mean FTND 6.2 Exclusions: Bupropion use (for SC); usual pharmacological criteria
Interventions	1. Varenicline 1 mg x 2/day, titrated for first wk 2. Placebo inactive tablets, same regimen All participants received 15‐minute SC counselling at each visit. CO tested and pill counts at each visit. Participants in both groups could reduce the dosage if they wished. TQD was set for wk 2 onwards (i.e. full dosage reached) Treatment period was 12 wks. Weekly pill counts to assess adherence Safety data were reviewed blind monthly by an external independent data safety and monitoring board (DSMB)
Outcomes	Primary: 7‐day PPA, CO‐verified, at 12 wks Secondary outcomes: 7‐day PPA at 24 wks; CA at 12, 24 wks Validation: CO < 10 ppm
Treatment type	Medication: VARENICLINE
Notes	New for 2016 update Funding from the National Insitute of Mental Health, and Pfizer
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method not stated, other than "stratified by gender"
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding (performance bias and detection bias) All outcomes	Low risk	"The treatment assignment was blinded to participating subjects, raters, investigators and statisticians"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	24 participants in each group completed treatment phase, and 24 (77%) and 20 (69%) completed full study in varenicline and placebo groups respectively Data were analysed using ITT with LOCF
Selective reporting (reporting bias)	Unclear risk	None noted
Other bias	Unclear risk	8 participants (4 in each arm) were on bupropion for depression; 3/15 varenicline quitters and 1/3 placebo quitters were on long‐term bupropion