To examine the efficacy of second-generation-antipsychotics (SGAs) in the treatment of negative symptoms in Schizophrenia.

Two meta-analyses were carried out using placebo or haloperidol as comparators. Studies were identified by searching for randomized, double-blind, placebo and/or haloperidol -controlled trials reporting data on efficacy of SGAs. Search was extended to the following databases: Pubmed, The Cochrane Central Register of Controlled Trials, Proquest Health and Medical Complete, Science Citation Index Expanded, and Current Contents Connect. The outcome measure used was the change in negative symptoms, choosing a standardized statistic (Cohen's d) to synthesize data.

A total of 46 homogeneous trials (Q=45.18, df=50, p=0.667, I2=0%) were included. In the placebo-controlled meta-analysis, the effect sizes (Cohen's d) obtained for amisulpride, haloperidol, olanzapine, quetiapine, risperidone and ziprasidone were 0.52, 0.34, 0.43, 0.36, 0.40 and 0.46, respectively, favoring active treatment against placebo (p< 0.001 in all cases). Comparing SGAs against haloperidol, showed just a statistically significant trend favoring SGA's in treatment of negative symptoms (Cohen's d = 0.15, p=0.008). Comparisons by drug showed a significant low and low-to-moderate standardized mean favoring SGA: Cohen's d = 0.34, p< 0.001; Cohen's d = 0.27, p< 0.001 and Cohen's d = 0.19, p=0.030, respectively for ziprasidone, risperidone and olanzapine.

Most antipsychotics (aminosulpride, haloperidol, olanzapine. quetiapine, risperidone, ziprasidone) are effective in treatment of negative symptoms, showing moderate effect sizes. Amisulpride and ziprasidone were slightly better than the rest of drugs when compared with placebo. Compared with haloperidol, SGA showed controversial results.