Negative symptoms are common in schizophrenia, but often difficult to differentiate from depression. They are associated with long-term impairment and do not respond well to current treatment approaches. Even though antidepressants are commonly prescribed in schizophrenia, their beneficial effect is still under debate. In the present study, we aimed to investigate the effect of serotonergic versus noradrenergic antidepressant add-on therapy on negative symptoms in schizophrenia.Fifty-eight patients with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and with predominant negative symptoms were randomized in a double-blind design to add-on treatment with citalopram, reboxetine, or placebo for 4 weeks. Analysis of covariance with repeated-measures design was used to compare improvement between treatment groups in scores of the Positive and Negative Syndrome Scale and the Hamilton Rating Scale for Depression. A χ2 test was used to compare responder rates between treatment groups.Repeated-measures analysis of covariance revealed no differences between treatment groups over time (treatment × time, not statistically significant) for Positive and Negative Syndrome Scale subscales. Although a subgroup analysis in subjects fulfilling the criteria for minor depression was suggestive of higher responder rates in the citalopram group compared with reboxetine, the results did not reach significance level.Our findings do not support a beneficial effect of adjunctive antidepressant treatment on negative symptoms in schizophrenia. However, depressive symptoms are reduced in patients with minor depression by citalopram but not reboxetine, which is in line with previous findings.