Narrative, unsystematic reviews revealed no differences in terms of efficacy between the various first-generation antipsychotics (FGAs) resulting in the psychopharmacological assumption of comparable efficacy between the different FGAs. Because this assumption contrasts with the clinical impression a high-quality systematic evaluation of this issue appeared highly necessary.

A systematic literature survey was applied to identify all randomized controlled trials (RCTs) that compared oral haloperidol with another oral FGA in schizophrenia. Primary outcome was clinically important response to treatment and secondary outcomes were overall acceptability, efficacy, tolerability, and specific adverse effects. Study selection and data extraction were carried out independently by at least two authors. All analyses were based on a random-effects model.

We included 63 RCTs with 2819 participants in our meta-analysis. In short term studies (up to 12 weeks) there was no statistically significant difference between haloperidol and the other FGAs in achieving response to treatment (40 RCTs, n=2132, RR 0.93 CI 0.87-1.00). In medium term trials haloperidol was significantly less effective than the other FGAs (1 RCT, n=80, RR 0.51 CI 0.37-0.69). There were no significant between-group differences regarding the other outcomes with the exception that haloperidol produced less akathisia in the medium term.

The findings of this meta-analysis support the statements of previous narrative, unsystematic reviews suggesting comparable efficacy of FGAs. Additionally, we demonstrated that haloperidol is characterized by a similar risk profile compared to the other FGAs. The results were limited by the low methodological quality in many of the included original studies.