Hernandez‐Avila 2004.

Methods	Randomized, double‐blind, placebo‐controlled trial
Participants	41 depressed people with alcohol dependence (20 men and 21 women; age (mean ± SD): 42.9 ± 8.6 years) Inclusion criteria: current DSM‐IV diagnoses of alcohol dependence and depression HRSD score ≥ 17 with a score ≥ 1 on item 1 aged 21‐65 years Exclusion criteria: history of major medical or psychiatric problems other than major depression or an anxiety disorder clinically significant baseline laboratory abnormalities or a positive pregnancy test current DSM‐IV diagnosis of drug dependence other than for alcohol or nicotine positive urine drug screen being treated with disulfiram or naltrexone or with any psychotropic drug being at serious suicide risk Participants with bipolar disorder were excluded.
Interventions	Drugs: nefazodone (200‐600 mg/day; 21 participants; 10 men and 11 women; age (mean ± SD): 43.1 ± 9.0 years) placebo (20 participants; 10 men and 10 women; age (mean ± SD): 42.7 ± 8.4 years) Psychotherapy: participants received manual‐guided supportive psychotherapy at each study visit Scheduled duration of treatment: 10 weeks Site: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA Setting: outpatients Route of administration: orally Starting dose: 100 mg twice daily then titrated up to a maximum dose of 300 mg twice daily Pattern of dose reduction: information not available
Outcomes	Depression: final HRSD score Alcohol dependence: rate of abstinent days (obtained from weekly drinking days) number of abstinent participants number of drinking days per week number of drinks per week number of heavy drinking days per week final DrinC score final GGT levels Anxiety: final STAI score Sleep quality: final PSQI score Dropouts Adverse effects
Notes	Baseline characteristics of participants Depression: primary depression: information not available duration: information not available HRSD score (mean ± SD): nefazodone = 16.3 ± 2.3; placebo = 17.3 ± 2.0 Alcohol dependence: drinks per drinking days (mean ± SD): nefazodone = 6.4 ± 6.5; placebo = 8.4 ± 5.2 duration: information not available being actively drinking: participants were not abstinent alcohol (their consumption had to be a mean ≥ 18 drinks per week for men or 14 drinks per week for women; heavy drinking (≥ 5 drinks for men and ≥ 4 drinks for women) on at least 1 day/week during the month preceding screening) length of abstinence at entry: 0 weeks Anxiety: STAI score (mean ± SD): nefazodone = 51.1 ± 9.9; placebo = 47.9 ± 9.4 Quality of sleep PSQI score (mean ± SD): nefazodone = 22.2 ± 4.5; placebo = 22.1 ± 3.9 Other psychiatric comorbidity: participants with other mental disorders were included. Other substance use disorders: participants with substance use disorders were excluded. Other characteristics of study Other pharmacological treatment offered: other pharmacological treatments were not allowed. Funding sources: study supported by NIH Grants P50‐AA03510, K24‐AA13736, and M01‐RR06192 and the Bristol‐Myers Squibb Co. Declarations of interest: information not available Other information After a baseline assessment, participants entered a 1‐week single‐blind placebo treatment, followed by random assignment to nefazodone or placebo groups.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Assignment to treatment groups used an urn randomization procedure, which balanced group assignment on sex, age, educational level, percentage of heavy drinking days, and severity of depressive symptoms at the time of the initial assessment.
Allocation concealment (selection bias)	Low risk	Method of concealment not reported but unlikely that selection bias was introduced.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and key study personnel ensured.
Blinding of outcome assessment (detection bias) objective	Low risk	No information provided on blinding of assessors.
Blinding of outcome assessment (detection bias) subjective	Unclear risk	No information provided on blinding of assessors.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Mixed model analysis used to examine variables measured at each visit during study. This procedure allows the inclusion of all cases (41 participants) by estimating individual trajectories even when other data points are missing because of participant attrition.
Selective reporting (reporting bias)	Low risk	All expected outcomes were reported.