Winhusen 2007.

Methods	Multi‐centre randomised controlled trial
Participants	Participants: 141 cocaine‐dependent patients; mean age 42.5 years; male 67%; African American 67%; full‐time employment 29%; married 18.5% Reporting cocaine use: 100% Route of cocaine administration: smoked 95%, intranasal 4%, intravenous 0.5%; oral 0.5% Cocaine use past 30 days: mean 17.2 (SD 9.4) Inclusion criteria: at least 28 years old, good physical health, at least 1 positive urine toxicology screen for cocaine metabolites, met DSM‐IV criteria for cocaine dependence Exclusion criteria: requirement of detoxification for alcohol, met DSM‐IV criteria for dependence on other substances than cocaine, alcohol, nicotine and marijuana; serious psychological disorders, enrolment in opiate substitution programme, current suicidal ideation, currently taking tiagabine or having medical condition exacerbated by tiagabine; pregnant or unwilling to use an adequate method of birth control (women)
Interventions	(1) tiagabine 20 mg/d, 70 participants; (2) placebo 71 participants All participants received 1 h of manualised individual cognitive‐behavioural therapy on a weekly basis Outpatients Duration: 12 weeks Country of origin: USA
Outcomes	Cocaine non‐use days (self report confirmed or disproved by urine BE levels) expressed as weekly proportion of non‐use days to total number of use and non‐use study days that week; Craving (BSCS); Addiction Severity (ASI); Clinical Global Impression scores (CGI‐O); Compliance
Notes	Supported by the National Institutes of Health, National Institute on Drug Abuse through contract N01‐DA‐9‐ 8095 (E. Somoza). The study medication and matching placebo were provided by Cephalon at no cost as a consultant for Alkermes, Astra Zeneca, Bristol Myers Squibb, Cephalon, Johnson & Johnson, Ortho‐McNeil and UCB Pharma
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Stratified randomization, balancing for gender and self‐report of cocaine use (<18 or ≥18 days of use in the last 30 days), was used to assign eligible participants to tiagabine or placebo within each study site"
Allocation concealment (selection bias)	Unclear risk	Information not reported
Blinding of participants and personnel (performance bias) objective outcomes	Low risk	Study declared as double‐blind Quote: "Participants assigned to placebo took tablets that looked identical to the tiagabine tablets and were scheduled to take the same number of tablets as those in the tiagabine condition"
Blinding of participants and personnel (performance bias) subjective outcomes	Low risk	Study declared as double‐blind Quote: "Participants assigned to placebo took tablets that looked identical to the tiagabine tablets and were scheduled to take the same number of tablets as those in the tiagabine condition"
Blinding of outcome assessment (detection bias) objective outcomes	Low risk	Information not reported Comment: objective outcomes unlikely to be biased by lack of blinding
Blinding of outcome assessment (detection bias) subjective outcomes	Unclear risk	Information not reported
Incomplete outcome data (attrition bias) All outcomes	High risk	Only 56% of participants completed the study; study completion rates did not differ significantly between tiagabine (54%) and placebo (58%) treatment groups (Chi2 = 0.17, df = 1, P value > 0.05) Reason for discontinuation reported and not significantly different between groups Comment: high dropout rate; per‐protocol analysis
Selective reporting (reporting bias)	Low risk	Study protocol is not available, but published reports include all expected outcomes, including those that were prespecified in the Methods section

ADHD: attention deficit hyperactivity disorder.
 CRES: Cocaine Rapid Efficacy Screening Trial.
 DSM: Diagnostic and Statistical Manual of Mental Disorders.
 MMT: methadone maintenance treatment.