Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. doi:10.1016/ s0140-673(08)61764-X [published online

Background Because of the debate about whether second-generation antipsychotic drugs are better than fi rst-generation antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the eff ects of these two types of drugs in patients with schizophrenia. Methods We compared nine second-generation antipsychotic drugs with fi rst-generation drugs for overall effi cacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-eff ects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21 533 participants. We excluded open studies because they systematically favoured second-generation drugs. Four of these drugs were better than fi rst-generation antipsychotic drugs for overall effi cacy, with small to medium eff ect sizes (amisulpride −0·31 [95 % CI −0·44 to −0·19, p<0·0001], clozapine −0·52 [−0·75 to −0·29, p<0·0001], olanzapine −0·28 [−0·38 to −0·18, p<0·0001], and risperidone −0·13 [−0·22 to −0·05, p=0·002]). The other second-generation drugs were not more effi cacious than the fi rst-generation drugs, even for negative symptoms. Therefore effi cacy on negative symptoms cannot be a core component of atypicality. Second-generation antipsychotic drugs induced fewer extrapyramidal side-eff ects than did haloperidol (even at low doses). Only a few have been shown to induce fewer extrapyramidal side-eff ects than low-potency fi rst-generation antipsychotic drugs. With the exception of aripiprazole and ziprasidone, second-generatio