Haloperidol Dose When Used as Active Comparator in Randomized Controlled Trials With Atypical Antipsychotics in Schizophrenia: Comparison With Officially Recommended Doses
J Clin Psychiatry 2006;67:897-903
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Objective: To determine the doses of haloperidol as a comparator drug
in randomized controlled trials (RCTs) with atypical antipsychotics in patients
with schizophrenia and to compare these doses with the officially recommended
doses for haloperidol in the United States and the United Kingdom.
Data Sources: We searched for RCTs conducted and published in English
in full before January 2005 in which atypical antipsychotics were compared with
haloperidol for the treatment of schizophrenia. We searched for Cochrane
Reviews in which 1 of the following atypical antipsychotics was evaluated for
the treatment of patients with schizophrenia, schizophreniform psychosis, or
other primary psychosis: amisulpride, aripiprazole, olanzapine, quetiapine,
risperidone, sertindole, and ziprasidone. For the gap between the end point of
inclusion of the studies in the Cochrane Reviews and January 2005, we
electronically searched the Cochrane Central Register of Controlled Trials for
any further RCTs in which atypical antipsychotics were compared with
haloperidol for the same indication. Search terms used were haloperidol and
schizophren* and haloperidol and psychotic*, as well as the names of the
selected atypical antipsychotics for the years that were not covered by the
Cochrane Reviews. For each study, the required dose and mean dose of
haloperidol were compared with officially recommended doses of haloperidol in
U.S. (Food and Drug Administration) and U.K. (British National Formulary)
Data Synthesis: In all of the included studies (N=49), the midpoints
of the required doses were above the midpoint of the official recommended doses
in the United States and United Kingdom for moderately ill patients. In 94%
(U.S.) and 80% (U.K.) of the studies, they were above the upper border of the
recommended doses. Compared with recommended doses for severely ill patients in
both the United Kingdom and United States (range, 6-15 mg daily), in 17 studies
(35%) the mean actual used dose was above the upper dose border for severely
ill patients (15 mg daily).
Conclusions: Nearly all randomized clinical trials used haloperidol
in doses that were higher than the official recommended doses for moderately
ill or even severely ill patients. Therefore, it is probable that the results
of the RCTs were affected by the high dose of haloperidol, hampering the
interpretation of the effects of atypical antipsychotics in their comparison