Muhonen 2008.

Methods	Randomized, double‐blind, comparative trial
Participants	80 depressed people with alcohol dependence (44 men and 36 women; age (mean ± SD): memantine = 47.5 ± 8.3 years; escitalopram = 47.9 ± 8.3 years) Inclusion criteria: aged 26‐65 years current DSM‐IV diagnoses of alcohol dependence and depression Exclusion criteria: other substance use dependence schizophrenia or other psychotic disorder and bipolar I and II disorder acute risk of suicide pregnant or breastfeeding severe untreated somatic problem or a serious liver dysfunction mental disability Participants with bipolar disorder were excluded.
Interventions	Drugs: escitalopram (20 mg/day; 40 participants) memantine (20 mg/day; 40 participants) Psychotherapy: no psychosocial intervention was offered. Scheduled duration of treatment: 26 weeks (6 months) Sites: 3 centres, Helsinki, Finland, and Europe. Setting: outpatients Route of administration: orally Starting dose: 5 mg/day increased at weekly intervals by 5 mg/day to 20 mg/day for both drugs. Pattern of dose reduction: information not available
Outcomes	Depression: final MADRS score final BDI score response (participants reporting that their depression was reduced) Alcohol dependence: number of abstinent participants Anxiety: final HRSA score final BAI score Cognitive functioning: final MMSE score final score in a retrieval wordlist Quality of life: final VAS score final SOFAS score Dropouts Adverse effects
Notes	Baseline characteristics of participants Depression: primary depression: information not available duration (mean ± SD): memantine = 1.9 ± 2.5 years; escitalopram = 3.9 ± 5.6 years MADRS score (mean ± SD): memantine = 25.8 ± 4.4; escitalopram = 26.8 ± 4.1 Alcohol dependence: AUDIT score (mean ± SD): memantine = 27.4 ± 7.1; escitalopram = 28.4 ± 6.4 number of heavy drinking days per week (mean ± SD): memantine = 2.9 ± 1.1; escitalopram = 3.1 ± 1.0 duration: participants had a history of heavy drinking for at least 10 years being actively drinking (rate of participants): memantine = 43.6%; escitalopram = 42.5% length of abstinence: abstinence not required but encouraged 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 medications prescribed by the patient's physician were allowed, except other antidepressants. Funding source: National Public Health Institute, the Finnish Foundation for Alcohol Research and Helsinki Health Center Research. Study medication provided by Lundbeck Oy Ab, Turku, Finland Declaration of interest: no conflicts of interest.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	All participants meeting the inclusion criteria were randomly assigned by an independent person to escitalopram or memantine groups using a 1:1 ratio and random permuted blocks (Vassar Statistics randomizing algorithm).
Allocation concealment (selection bias)	Low risk	Randomization was concealed until study database was locked on by an independent clinical study monitor.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Study medication was double‐dummy packed: participant took 2 tablets every time, 1 of which was the active medicine and 1 was an identical placebo for the second medication. The medication was labelled and controlled by an independent supplier.
Blinding of outcome assessment (detection bias) objective	Low risk	Outcome analysis was performed by an independent source.
Blinding of outcome assessment (detection bias) subjective	Low risk	Outcome analysis was performed by an independent source.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat analysis used.
Selective reporting (reporting bias)	Low risk	Data of all randomized participants were reported except for 1 participant due to an interrupted interview.