Altintoprak 2008.

Study characteristics
Methods	Study design: randomized controlled trial Country: Turkey Setting: hospital specialized addiction unit Eligibility criteria: individuals who were 18‐65 years of age, met criteria for alcohol dependence and depressive disorder, were experiencing a current depressive episode, but had no serious physical illness. Female participants also needed to be adequately protected against pregnancy. Excluded were individuals with another major psychiatric disorder, a history of psychiatric problems other than depressive disorder, the presence of organic brain disease, a history of hypersensitivity to mirtazapine or amitriptyline, pregnant or breastfeeding, other substance (non‐alcohol, tobacco, or caffeine) use disorder, and having consumed alcohol during the study. Duration of follow‐up: 56 days Informed consent: all participants provided written informed consent Ethical approvals: all procedures were approved by Ege University Ethics Committee
Participants	Sample size: 36 (20 mirtazapine, 16 amitriptyline) Description of target population: patients seeking primary healthcare with alcohol dependence and depression Age: 44.0 years (range 18‐65) Sex: 8.3% female Race/Ethnicity: not reported Marital status: 63.9% married Harmful alcohol use (baseline): Michigant Alcoholism Screening Test (MAST): 38.9 (SD=6.1) Co‐occurring disorders: 100% major depressive disorder and current depressive episode
Interventions	Type: pharmacologic Description: mirtazapine following alcohol detoxification with diazepam taper and vitamin B Duration and frequency: started with 15 mg/day. On the third day patients were increased to 30 mg/day. At the end of the first week dose was increased to 45 mg to 60 mg/day if severity of symptoms persisted Delivery and provider: clinician delivered capsules consumed orally Comparison group: amitriptyline (50 mg/day increased to 100 mg/day on third day and 125‐150 mg/day at end of first week if severity of symptoms persisted) following detoxification with diazepam taper and vitamin B
Outcomes	Primary outcome(s): alcohol craving Primary outcome measurement tool(s): alcohol craving questionnaire developed by study investigators Secondary outcome(s): State anxiety, trait anxiety, Depression Secondary outcome measurement tool(s): Spielberger State‐Trait Anxiety Inventory (STAI); Hamilton Depression Rating Scale (HDRS) Time points: 0, 7, 14, 28, 42, 56 days
Notes	Study funding and conflicts of interest: not reported Linked study records: none
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "At the end of the alcohol detoxification treatment with diazepam (approximately 10–14 days), the patients with HDRS scores 14 were included in the study and they were randomly allocated to mirtazapine or amitriptyline treatment groups." Pg. 315
Allocation concealment (selection bias)	Unclear risk	Drugs were administered in identical looking opaque capsules, but unclear if allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Both the clinicians and patients were blind to the treatment." Pg. 315
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Initially, 97 patients were enrolled in the study but after the detoxification period there were only 44 patients meeting the criteria for current major depressive disorder. Eight of the patients dropped out (three of the patients dropped out due to adverse effects of drugs, one of them dropped out due to an another psychiatric disorder emerged during the study, two patients dropped out due to alcohol consumption in the treatment setting, and two patients decided not to remain in the study). Thirty‐six patients completed the study. Dropouts were not included in the analysis due to missing data." Pgs. 315‐316
Selective reporting (reporting bias)	Unclear risk	No protocol available