title: Comparison of incidence rates of cerebrovascular accidents and transient ischaemic attacks in observational cohort studies of patients prescribed risperidone, quetiapine or olanzapine in general practice in England including patients with dementia.
abstract: Following changes in the safety information on the use of risperidone and olanzapine in elderly patients with dementia, data from prescription-event monitoring (PEM) studies of risperidone, quetiapine and olanzapine were examined. The aim was to compare incidence rates for events reported as cerebrovascular accident (CVA) and transient ischaemic attack (TIA) during the first 180 days of treatment in patients prescribed atypical antipsychotics for dementia or other indications, because of the possible association between dementia and stroke in users of atypical antipsychotics. A retrospective analysis of data from the three observational studies was conducted using Poisson regression modelling and survival analysis. Within the risperidone, quetiapine and olanzapine cohorts, 23 (0.30%), 6 (0.35%) and 10 (0.11%) patients respectively, were reported to have had a CVA/TIA event. Age, sex and indication (dementia or other) were identified as important confounding variables; age being the most important. The crude rate ratios (RRs) for CVA/TIA for risperidone or quetiapine vs. olanzapine indicated an approximate threefold relative difference in rate during the first six months but after adjustment for age, sex and indication, the RRs were non-significant (1.2 (95% CI 0.5,3.0) and 2.1 (95% CI 0.6,7.7), respectively). For risperidone vs. quetiapine, crude and adjusted RRs were not significantly different. Of the three drugs, the time to event was shortest for risperidone and also shortest for risperidone or quetiapine users where the indication was dementia. The age and sex adjusted RR of CVA/TIA in patients prescribed risperidone for dementia vs. other indications was 6.7 (95% CI 2.4,18.9). The adjusted RRs for quetiapine, according to indication, could not be calculated due to missing information on age and sex. There were no cases of CVA/TIA with dementia for olanzapine, thus the RRs and time to event curves according to indication could not be examined. This study revealed no significant difference in the adjusted RR of CVA/TIA events in the first 180 days of treatment in patients prescribed risperidone or quetiapine when compared with olanzapine. However, dementia appears to be an important risk factor. These results should be considered alongside other pharmacoepidemiological studies on this topic.
authors.affiliation: Drug Safety Research Unit, Bursledon Hall, Blundell Lane, Southampton, UK. deborah.layton@dsru.org
authors.forename: Deborah
authors.initials: D
authors.lastname: Layton
authors.forename: Scott
authors.initials: S
authors.lastname: Harris
authors.forename: Lynda V
authors.initials: LV
authors.lastname: Wilton
authors.forename: Saad A W
authors.initials: SA
authors.lastname: Shakir
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D003704:Dementia / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use; D004739:England / Q000453:epidemiology; D005194:Family Practice / Q000379:methods / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D015994:Incidence; D002546:Ischemic Attack, Transient / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011358:Product Surveillance, Postmarketing / Q000379:methods / Q000706:statistics & numerical data; D000069348:Quetiapine Fumarate; D012189:Retrospective Studies; D012307:Risk Factors; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone; D000077152:Olanzapine