A Cochrane review [Abstract] 1included 17 RCTs and 877 participants with schizophrenia. Thirteen studies were conducted in hospitals. The follow-up time was between 2 and 12 weeks for all studies. The low-potency, first-generation antipsychotic comparators were chlorpromazine (8 trials), levomepromazine (2 trials), mesoridazine (one trial), perazine (2 trials) and thioridazine (4 trials). There was no clear evidence that haloperidol was superior to low-potency antipsychotic drugs in terms of clinical response (haloperidol 40%, low-potency drug 36%, RR 1.11, CI 0.86 to 1.44; 14 RCTs, n = 574). There was also no clear evidence of benefit for either group in acceptability of treatment with equivocal difference in the number of participants leaving the studies early due to any reason (haloperidol 13%, low-potency antipsychotics 17%, RR 0.82, CI 0.38 to 1.77; 11 RCTs, n = 408). Similar equivocal results were found between groups for experiencing at least one adverse effect (haloperidol 70%, low-potency antipsychotics 35%, RR 1.97, CI 0.69 to 5.66; 5 RCTs n = 158). More participants from the low-potency drug group experienced sedation (haloperidol 14%, low-potency antipsychotics 41%, RR 0.30, CI 0.11 to 0.82; 2 RCTs, n = 44), orthostasis problems (haloperidol 25%, low-potency antipsychotics 71%, RR 0.35, CI 0.16 to 0.78; 1 RCT, n = 41) and weight gain (haloperidol 5%, low-potency antipsychotics 29%, RR 0.22, CI 0.06 to 0.81; 3 RCTs, n = 88). In contrast, the outcome 'at least one movement disorder' was more frequent in the haloperidol group (haloperidol 72%, low-potency antipsychotics 41%, RR 1.64, CI 1.22 to 2.21; 5 RCTs, n = 170). No data were available for death or quality of life. The results of the primary outcome were robust in several subgroup and sensitivity analyses.
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, short follow-up time) and imprecise results (few patients and wide confidence intervals).
A Cochrane review [Abstract] 2 included 14 studies with a total of 794 subjects. Most of the studies comparing haloperidole with chlorpromazine were conducted before 1980. Nine compared oral formulations of both compounds, and five compared intramuscular formulations. The efficacy outcome 'no significant improvement' tended to favour haloperidol, but this difference was not statistically significant (9 RCTs, n=400, RR 0.81 CI 0.64 to 1.04). Movement disorders were more frequent in the haloperidol groups ('at least one extrapyramidal side effect': 6 RCTs, n=37, RR 2.2 CI 1.1 to 4.4, NNH 5 CI 3 to 33), while chlorpromazine was associated with more frequent hypotension (5 RCTs, n=175, RR 0.31 CI 0.11 to 0.88, NNH 7 CI 4 to 25). Haloperidol was associated with significantly fewer people leaving the studies early (13 RCTs, n=476, RR 0.26 CI 0.08 to 0.82). Only one trial had a duration of more than six months. Similar trends were found when studies comparing intramuscular formulations and studies comparing oral formulations were analysed separately.
Comment: The quality of evidence is downgraded by study quality (inadequate follow up) and imprecise results (few patients and wide confidence intervals).
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