Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis

摘要: Summary Background The question of which antipsychotic drug should be preferred for the treatment schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on randomised evidence. We aimed to integrate available evidence create hierarchies comparative efficacy, risk all-cause discontinuation, major side-effects drugs. Methods did Bayesian-framework, multiple-treatments meta-analysis (which uses both direct indirect comparisons) controlled trials compare 15 drugs placebo in acute schizophrenia. searched Cochrane Schizophrenia Group's specialised register, Medline, Embase, Central Register Controlled Trials, ClinicalTrials.gov reports published up Sept 1, 2012. Search results were supplemented by from US Food Drug Administration website data requested pharmaceutical companies. Blinded, patients with or related disorders eligible. excluded done predominant negative symptoms, concomitant medical illness, resistance, those stable patients. Data seven outcomes independently extracted two reviewers. primary outcome was as measured mean overall change symptoms. also examined weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, sedation. Findings identified 212 suitable trials, 43 049 participants. All significantly more effective than placebo. standardised differences 95% credible intervals were: clozapine 0·88, 0·73–1·03; amisulpride 0·66, 0·53–0·78; olanzapine 0·59, 0·53–0·65; risperidone 0·56, 0·50–0·63; paliperidone 0·50, 0·39–0·60; zotepine 0·49, 0·31–0·66; haloperidol 0·45, 0·39–0·51; quetiapine 0·44, 0·35–0·52; aripiprazole 0·43, 0·34–0·52; sertindole 0·39, 0·26–0·52; ziprasidone 0·30–0·49; chlorpromazine 0·38, 0·23–0·54; asenapine 0·25–0·51; lurasidone 0·33, 0·21–0·45; iloperidone 0·22–0·43. Odds ratios compared discontinuation ranged 0·43 best (amisulpride) 0·80 worst (haloperidol); 0·30 (clozapine) 4·76 sedation 1·42 8·82 (clozapine). Standardised gain varied −0·09 (haloperidol) −0·74 (olanzapine), increase 0·22 (aripiprazole) −1·30 (paliperidone), prolongation 0·10 (lurasidone) −0·90 (sertindole). Efficacy not substantially after removal groups, when dose, percentage withdrawals, extent blinding, industry sponsorship, study duration, chronicity, year publication accounted meta-regressions sensitivity analyses. Interpretation Antipsychotics differed small but robust seen efficacy. Our findings challenge straightforward classification antipsychotics into first-generation second-generation groupings. Rather, different domains help clinicians adapt choice needs individual These considered mental health policy makers revision clinical practice guidelines. Funding None.