Haloperidol is one of the most frequently prescribed medications for the treatment of psychosis worldwide, but previous narrative, unsystematic reviews found no differences in efficacy between various first-generation (“conventional,” “typical”) antipsychotic agents for schizophrenia and schizophrenia-like psychosis. A review in the Cochrane Library assessed 63 randomized controlled trials (RCTs) comparing any oral form of haloperidol at any dose with another oral first-generation antipsychotic drug (excluding low-potency antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine, perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia-like psychosis. The primary outcome was clinically important response to treatment and secondary outcomes were global state, mental state, behavior, 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.

The antipsychotics most frequently compared to haloperidol were bromperidol (n = 9), loxapine (n = 7), and trifluoperazine (n = 6) in studies published from 1962–1993 with small sample sizes and incomplete reporting of predefined outcomes. All results for the main outcomes were based on very low or low quality data. In the trials conducted for up to 12 weeks (short-term), no clear differences between haloperidol and the pooled group of comparison first-generation antipsychotics for the primary outcome were evident. Haloperidol was less effective than other first-generation antipsychotic groups in medium-term (>12–26 weeks) studies, but this result was based on only one trial. There was statistically significant evidence indicating that haloperidol produced less akathisia in the medium-term trials than other antipsychotic medications, although there was no statistically significant difference between-global state, other mental state outcomes, behavior, and leaving the study early (due to any reason, inefficacy, or adverse effects).

Haloperidol and other evaluated first-generation antipsychotic agents had comparable efficacy and similar acceptability and tolerability in these results, but the authors warn that the low quality evidence from these RCTs should be taken into account in interpretation.