Hatsukami 2004.

Methods	BUPROPION Randomized controlled trial Setting: 12 clinical trial sites, USA Recruitment: community volunteers
Participants	594 smoker of >= 20 CPD wanting to reduce amount smoked. Not quit for > 3m in previous year, at least 2 failed quit attempts including 1 with NRT, not currently depressed, 6% had history of MDD. Excludes 15 who took no study medication.
Interventions	Not a cessation trial 1. Bupropion 300 mg/day, 26w 2. Placebo Both arms: written materials suggesting reduction techniques, monthly brief individual counselling, telephone contact 2 days, 12 days, 5w after target reduction date. Participants indicating a willingness to quit at any time were enrolled in a 7w cessation programme with weekly visits followed by 19w of follow up
Outcomes	Abstinence 6m after quit date (denominator 594; 214 entered cessation phase Validation: urine cotinine
Notes	Not used in main analysis 38% of bupropion and 34% of placebo group entered cessation phase. Median time to attempting cessation shorter in bupropion group Funding: GlaxoSmithKline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Subjects were assigned randomly using a computer‐generated schedule..."
Allocation concealment (selection bias)	Unclear risk	Allocation concealment not described.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"Double‐blind," unclear who was blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	Very high levels of attrition (at 6 months, 43% placebo and 39% control followed up). For cessation analyses, subjects who dropped out were considered to have resumed smoking [after withdrawal date].