Kranzler 2006 arm A.

Methods	Randomized, double‐blind, placebo‐controlled trial
Participants	189 depressed people with alcohol dependence (123 men; 66 women; age (mean ± SD): placebo = 44.0 ± 8.0 years; sertraline = 41.7 ± 9.4 years) Inclusion criteria: aged 21‐65 years current DSM‐IV diagnoses of alcohol dependence and depression (modified: to meet DSM‐IV criteria for depression, except that symptoms could have occurred during a period of heavy alcohol use) HRSD score ≥ 17 Exclusion criteria: pregnant, nursing, or of childbearing potential not using an effective method of contraception clinically significant co‐occurring psychiatric or medical diagnoses, including dependence on any psychoactive substance other than alcohol or nicotine during the preceding year current treatment with disulfiram, naltrexone, or psychotropic medication serum aminotransferase levels or other measures of hepatic function that were > 250% of normal significant suicidal risk Participants with bipolar disorder were excluded.
Interventions	Drugs: sertraline (up to 200 mg/day; 89 participants) placebo (100 participants) Psychotherapy: at each study visit, participants received supportive therapy delivered according to a manual developed specifically for study consisting in: general support for abstinence promotion of compliance monitoring of medication adverse effects Scheduled duration of treatment: for up to 10 weeks Sites: 13 investigative sites in USA Setting: outpatients Route of administration: orally Starting dose: 50 mg/day Pattern of dose reduction: participants who achieved a satisfactory therapeutic response and who wished to continue treatment beyond the end of week 10 were continued double‐blind on the same medication they were taking at the end of week 10 for an additional 14‐week period; participants who did not continue in the extension study were tapered off medication by reducing the daily dose by one capsule every 2 to 3 days until the medication was completely discontinued.
Outcomes	Depression: final HRSD score (obtained from a figure) difference between baseline and final HRSD score response Alcohol dependence: rate of abstinent days (obtained from a figure) Dropout Adverse effects
Notes	Baseline characteristics of participants Depression: primary depression (rate of participants): 100% duration: information not available number of DSM‐IV criteria (mean ± SD): sertraline = 6.7 ± 1.0; placebo = 6.8 ± 1.2 HRSD score (mean ± SD): sertraline = 20.3 ± 2.8; placebo = 20.9 ± 4.0 Alcohol dependence: number of DSM‐IV criteria (mean ± SD): sertraline = 5.6 ± 0.9; placebo = 5.5 ± 0.9 number of drinks per week (mean ± SD): sertraline = 45.9 ± 32.2; placebo = 63.1 ± 44.4 duration (mean ± SD): sertraline = 11.9 ± 9.0 years; placebo = 11.9 ± 9.9 years being actively drinking: participants had to have drunk a mean of 18 drinks weekly for men or 14 drinks weekly for women and at least 1 heavy drinking day per week during the month before screening length of abstinence: at least 4 days with no heavy drinking and no more than 16 days of abstinence Other psychiatric comorbidity: participants with other mental disorders were excluded. 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 source: supported by Pfizer Pharmaceuticals. Manuscript preparation supported by NIH grant K24 AA13736. Declarations of interest: information not available. Other information In the original study, 328 participants were divided into the 2 groups on whether initially elevated HRSD score declined with cessation of heavy drinking: HRSD score ≥ 17 (189 participants); HRSD score ≤ 16 (139 participants). In the present meta‐analysis, participants were divided into 2 substudies: Kranzler 2006 arm A (189 participants with HRSD scores ≥ 17); Kranzler 2006 arm B (139 participants which HRSD scores ≤ 16). Both the substudies (Kranzler 2006 arm A; Kranzler 2006 arm B) were included in the 'Effects of interventions: Antidepressants versus placebo' comparison. Unfortunately, the original study did not report the adverse events for the single substudies.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomization schedule.
Allocation concealment (selection bias)	Unclear risk	Assignment to medication group was done according to a computer‐generated randomization schedule for groups A and B, with the medication groups within each stratum balanced for recent outpatient/inpatient status. Despite random assignment, participants who received placebo were older, reported more drinks per week during the pretreatment period, and had higher CGI depression scores at baseline.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement.
Blinding of outcome assessment (detection bias) objective	Low risk	No information on the blinding of outcome assessors.
Blinding of outcome assessment (detection bias) subjective	Unclear risk	No information on the blinding of outcome assessors.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All analyses used an intention‐to‐treat approach.
Selective reporting (reporting bias)	Low risk	All expected outcomes were reported. However, some of them were reported only as a % reduction (e.g. BDI score).