Antidepressants as add-on treatment to antipsychotics for people with schizophrenia and pronounced negative symptoms: A systematic review of randomized trials

Abstract The aim of our meta-analysis was to review the evidence base for the efficacy and safety of antipsychotic and antidepressant combinations in the treatment of the negative symptoms of schizophrenia and schizophrenia-like psychoses. Randomized controlled trials comparing the combination of antidepressants and antipsychotics with antipsychotics alone for patients with pronounced negative symptoms in schizophrenia were searched for by accessing the register of randomized controlled trials of the Cochrane Schizophrenia group. The studies identified were independently inspected and their quality assessed by two reviewers. The principal outcome of interest was the reduction of negative symptoms. Dichotomous data were analyzed using the relative risk and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. It was possible to include seven trials ( n  = 202) examining antidepressants as add-on to antipsychotics in this review. Except for one study, all included studies used first generation antipsychotics. While there was often merely a trend in favour of augmentation of antipsychotics with antidepressants in the small single studies, the meta-analytic combination resulted in a statistically significant superiority in the outcome reduction of negative symptoms as a whole. Statistically significant differences between groups in terms of specific subscores of the SANS were found, but the results were inconsistent. The combination of antipsychotics and antidepressants may be more effective in treating negative symptoms of schizophrenia than antipsychotics alone, but this finding needs to be corroborated by further large trials.