Haloperidol versus first‐generation antipsychotics for the treatment of schizophrenia and other psychotic disorders

Background Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences in terms of efficacy between the various first‐generation (“conventional”, "typical") antipsychotic agents. This established the unproven psychopharmacological assumption of a comparable efficacy between the first‐generation antipsychotic compounds codified in textbooks and treatment guidelines. Because this assumption contrasts with the clinical impression, a high‐quality systematic review appeared highly necessary. Objectives To compare the efficacy, acceptability, and tolerability of haloperidol with other first‐generation antipsychotics in schizophrenia and schizophrenia‐like psychosis. Search methods In October 2011 and July 2012, we searched the Cochrane Schizophrenia Group’s Trials Register, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. To identify further relevant publications, we screened the references of all included studies and contacted the manufacturers of haloperidol for further relevant trials and missing information on identified studies. Furthermore, we contacted the corresponding authors of all included trials for missing data. Selection criteria We included all randomised controlled trials (RCTs) that compared oral haloperidol with another oral first‐generation antipsychotic drug (with the exception of the low‐potency antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine, perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia‐like psychosis. Clinically important response to treatment was defined as the primary outcome. Secondary outcomes were global state, mental state, behaviour, overall acceptability (measured by the number of participants leaving the study early due to any reason), overall efficacy (attrition due to inefficacy of treatment), overall tolerability (attrition due to adverse events), and specific adverse effects. Data collection and analysis At least two review authors independently extracted data from the included trials. The methodological quality of the included studies was assessed using The Cochrane Collaboration`s 'Risk of bias' tool. We analysed dichotomous outcomes with risk ratios (RR) and continuous outcomes with mean differences (MD), both with the associated 95% confidence intervals (CI). All analyses