In this study, we investigated the impact of Problem Drink on depression. Forty participants with depression were divided into 2 groups: non-Problem Drinker (NPD) group (n = 22) and Problem Drinker (PD) group (n = 18) according to Alcohol Use Disorder Identification Test (AUDIT) score (NPD < 12, PD > or = 12). Depression was assessed by the Mini-International Neuropsychiatric Interview. The effect of medication on depressive symptoms was monitored over 12 weeks using the Hamilton Rating Scale for Depression (HAM-D). Significant improvement in HAM-D score was observed at 2 weeks in NPD patients but not until 4 weeks in PD patients. Total HAM-D scores were lower in NPD than in PD patients at the end of the treatment period. Therapeutic doses (dose of antidepressant used was equivalent to greater than 75 mg of imipramine) of antidepressants resulted in significant improvement in HAM-D scores at 2 weeks in NPD patients, but not until 8 weeks in PD patients and brought lower HAM-D scores in NPD than in PD patients at the end of the treatment period. The AUDIT score and total alcohol consumption during the study period were negatively correlated to the improvement in HAM-D score. In NPD patients, the level of education of patients in remission was higher than those by patients not in remission. In contrast, level of education of patients in remission were similar to those in PD patients not in remission. The above results suggest that co-occurrence of alcohol use disorders with depression is associated with a lower response to antidepressants which may reflect not only the result of biological alterations in the brain by chronic ethanol ingestion but also an inhibitory effect of ethanol on antidepressant action in the brain. Drinking-related cognitive dysfunction may also relate to the decreased response to treatment in the depressed patients with comorbid Problem Drinker.