Haloperidol dose for the acute phase of schizophrenia.
BACKGROUND
Haloperidol is a benchmark, accessible antipsychotic against which the effects of newer treatments are gauged.


OBJECTIVE
The primary goal of this review is to determine the best range of doses for haloperidol for the treatment of people acutely ill with schizophrenia.


METHODS
The reviewers searched Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (1999, Issue 2), The Cochrane Schizophrenia Group's Register (December 1999), EMBASE (1980-1999), MEDLINE (1966-1999) and PsycLIT (1887-1999). They also inspected all references of all identified trials and included studies sought as a citation on SCISEARCH database (1980-1999). Authors of identified studies and pharmaceutical companies were also contacted.


METHODS
Studies were selected if they involved people being treated for acute schizophrenia, randomised to two or more dose ranges of non-depot haloperidol, and if they reported clinically meaningful outcomes.


METHODS
The reviewers independently and blindly inspected citations (10% reliability check), they ordered papers, and reliably re-inspected and quality assessed the full reports. The reviewers, again working independently, also extracted data. For homogeneous dichotomous data the relative risk (RR), 95% confidence intervals (CI) were calculated on an intention-to-treat basis. Reviewers assumed that people who left the study early or were lost to follow-up had a negative outcome. Weighted mean differences (WMD) were calculated for continuous outcomes that reported intention to treat (ITT), last observation carried forward (LOCF) data. Data was excluded if loss to follow-up was greater than 50%.


RESULTS
Sixteen trials with nineteen different randomised dose comparisons were included. No studies reported data on relapse rates, quality of life and none compared >1.5-3.0 mg/day haloperidol to higher dose ranges. Using low doses (>3-7.5mg/day) did not clearly result in loss of efficacy (no clinically important improvement in global state, versus >7.5-15mg/day n=48, 1 RCT, RR 1.09 CI 0.7 to 1.8; versus >15-35mg/day n=81, 2 RCTs, 0.95 CI 0.8 to 1.2). Doses of haloperidol in the range of >3-7.5 mg/day had a lower rate of development of clinically significant extrapyramidal adverse effects than higher doses (clinically significant extrapyramidal adverse effects, versus >7.5-15mg/day n=64, 2 RCTs, RR 0.12 CI 0.01 to 2.1; versus >15-35mg/day n=144, 3 RCTs RR 0.59 CI 0.5 to 0.8, NNH 3 CI 2 to 6; versus >35mg/day n=86, 2 RCTs, RR 0.70 CI 0.5 to 1.1). All other comparisons between dose ranges did not yield statistically significant differences, but several, particularly with lower dose ranges, were underpowered to detect clinically meaningful differences.


CONCLUSIONS
No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.
Department of Psychiatry, University of British Columbia, 1081 Burrard St., Rm 306, Comox Building, Vancouver, British Columbia, Canada, V6Z 1Y6. waraich@interchange.ubc.ca
P S
PS
Waraich
C E
CE
Adams
M
M
Roque
K M
KM
Hamill
J
J
Marti
D000208:Acute Disease; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D006220:Haloperidol / Q000008:administration & dosage*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D006220:Haloperidol