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Fluoxetine, trazodone and ritanserin are more effective than placebo when used as add-on therapies for negative symptoms of schizophrenia

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Are antidepressents effective add-ons to antipsychotics for the treatment of negative symptoms in chronic schizophrenia?


Change in negative symptoms.



Systematic review and meta-analysis.

Data sources

PubMed, Cochrane Library, EMBASE, CINAHL and PsycINFO were searched in August 2009, and supplemented with handsearch for relevant studies.

Study selection and analysis

Randomised, placebo-controlled trials published were eligible. Studies were excluded if antidepressant was used to treat an explicit comorbid psychiatric disorder, for example, postpsychotic depression, obsessive-compulsive disorder, emergence of major depression in remitted schizophrenia; if an antidepressant was not used as add-on medication; or if an antidepressant was not normally classified under a standard antidepressant category.

Main results

22 randomised controlled trials (RCTs) met inclusion criteria; comparing 23 add-on antidepressant interventions with placebo. The total sample size was 819 (416 in pooled experimental groups). Onset of schizophrenia was in early adulthood for all participants with an average duration of illness over 15 years. There was a greater proportion of …

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  • Sources of funding Supported in part by the Quality of Life Research and Development Foundation.


  • Competing interests None.