Background: Antidepressants can have an effect on depressive symptoms in participants with comorbid drug or alcohol dependence and mood disorder, but their effect on drug use is not known. It has been suggested that adding psychosocial intervention to antidepressants would enhance the effect on drug use.Method: A meta-analysis was conducted on trials of antidepressants for this comorbidity with and without psychosocial treatment.Results: Studies using cognitive-behavioural therapy (CBT) found no medication effect, whereas with no intervention, medication was superior to placebo, manualised counselling falling in between.Conclusion: There is no evidence that antidepressant medication is more efficacious in reducing drug use with conjunctive psychosocial treatment. Antidepressant medication and psychotherapy may both be useful in the treatment of substance-dependent depressed patients, but combining psychotherapy and medication may only be useful in patients failing to respond to one treatment.