Butterworth 1971b.

Methods	Randomized, placebo‐controlled, double‐blind trial
Participants	40 depressed people with alcohol dependence (all men; mean age: majority aged 31‐50 years) Inclusion criteria: alcohol dependence requiring involuntarily admission for detoxification diagnoses of depression according to clinical impression LDRS score ≥ 12 Exclusion criteria: hepatic disease organic brain damage psychosis Participants with bipolar disorder: information not available
Interventions	Drugs: imipramine (75‐200 mg/day; 20 participants) placebo (20 participants) Psychotherapy: none Scheduled duration of treatment: 3 weeks Site: Alcoholic Treatment Service, East Louisiana State Hospital, Jackson, LA, USA Setting: inpatients for first 3‐4 days for treatment of alcohol withdrawal, then 3 weeks for trial Route of administration: orally Starting dose: 75 mg/day increased to maximum 200 mg/day according to individual requirements reduced if indicated by adverse effects Pattern of dose reduction: information not available
Outcomes	Depression: difference between basal and final LRDS score response Alcohol dependence: data not available Dropouts Adverse effects
Notes	Baseline characteristics of participants Depression: primary depression: information not available duration: information not available after detoxification and washout, LDRS score (mean ± SD): imipramine = 16.0 ± 3.1; placebo = 15.6 ± 3.3. Alcohol dependence: duration: for 24 participants = 1‐5 years; for 16 participants ≥ 10 years; severity: all participants required involuntarily admission for detoxification, many participants had been hospitalized repeatedly for detoxification, in some instances as many as 30 times; being actively drinking: participants were abstinent; length of abstinence: 0.5 weeks 3‐4 days for the treatment of alcohol withdrawal). Other psychiatric comorbidity: information not available. Other substance‐use disorders: information not available. Other characteristics of study Other pharmacological treatment offered: participants received pharmacological treatment to control the acute symptoms of alcohol withdrawal for 3‐4 days. Funding sources: information not available Declaration of interest: information not available
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Random allocation stated. No further details provided.
Allocation concealment (selection bias)	Unclear risk	Method of concealment not described.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blind stated. Medication and placebo prepared to appear identical. No specific reference made to blinding of participants and personnel.
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	High risk	Methods applied to account for missing data not described. Intention‐to‐treat approach not reported. People who left study were replaced by other people ("One patients taking imipramine left the hospital ... and global evaluation were omitted. Two additional patients left without permission just after entering the trial, and were therefore replaced in the study. One had received six doses of imipramine and the other one placebo").
Selective reporting (reporting bias)	Unclear risk	Information insufficient to permit judgement.