Background: Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue.

Aims: To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia.

Method: Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms.

Results: There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (-0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin.

Conclusions: Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.