Risk of extrapyramidal syndromes with haloperidol, risperidone, or olanzapine.
OBJECTIVE
To compare the risk of extrapyramidal syndrome (EPS) between risperidone, olanzapine, and haloperidol, taking into account patients' past antipsychotic drug use and past EPS.


METHODS
Data were obtained from the PHARMO-database, containing filled prescriptions of 450,000 community-dwelling people in the Netherlands from 1986 through 1999. We defined cohorts of first-time users of haloperidol, risperidone, or olanzapine aged 15 to 54 years. In the first 90 days of treatment, we assessed the occurrence of EPS, defined as first use of any antiparkinsonian agent. We estimated relative risks of EPS for risperidone and olanzapine versus haloperidol using a Cox proportional hazards model. Patients were subdivided according to prior use of antipsychotic and antiparkinsonian drugs.


RESULTS
We identified 424 patients starting treatment with haloperidol, 243 with risperidone, and 181 with olanzapine. Prior use of antipsychotic plus antiparkinsonian medication was significantly more frequent among users of risperidone and olanzapine than in those using haloperidol (36.2%, 40.3%, and 4.5%, respectively; p < 0.001). Within most subgroups of comparable treatment history, patients using risperidone and olanzapine showed reduced risks of EPS compared with haloperidol, although some of these findings did not reach statistical significance (RR 0.03-0.22). However, this was not observed for patients using risperidone who had experienced EPS in the past (RR 1.30; 95% CI 0.24 to 7.18).


CONCLUSIONS
In general, we observed reduced risks of EPS for risperidone and olanzapine compared with haloperidol within subgroups of patients with a similar treatment history. However, the added value of risperidone in patients who have experienced EPS in the past needs further study.
Schillevoort
I
I
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, PO Box 80082, 3508 TB, Utrecht, The Netherlands. i.e.r.m.schillevoort@pharm.uu.nl
de Boer
A
A
Herings
R M
RM
Roos
R A
RA
Jansen
P A
PA
Leufkens
H G
HG
D000293:Adolescent; D000328:Adult; D000978:Antiparkinson Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000453:epidemiology; D001569:Benzodiazepines; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D012307:Risk Factors; D018967:Risperidone / Q000009:adverse effects*
D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine