A new analysis of patient records in the UK confirms that prescribing antipsychotics to people with dementia is not only ethically dubious but carries a serious risk of stroke, particularly when the newer atypical antipsychotics are used.

Researchers from the London School of Hygiene and Tropical Medicine found that any patients given antipsychotics were 1.73 times more likely to have a stroke than when they were not taking the drugs, with 1.69 times the risk on typical and 2.32 times on atypical antipsychotics.

When those patients had recorded dementia, they were 3.50 times more likely to have a stroke while on antipsychotics than when not taking the drugs. The risk was slightly lower at 3.26 times the non-exposed population on typical antipsychotics but rose to 5.86 times when patients took atypical antipsychotics.

Patients without recorded dementia were 1.41 times more likely to have a stroke if they were taking antipsychotics, with the risk dropping marginally to 1.40 times with typical antipsychotics but increasing to 1.90 times on the atypicals.

The team led by Ian Douglas, research fellow in the School’s Department of Epidemiology and Population Health, used data from the General Practice Research Database, which includes clinical information on more than six million patients registered at over 400 general practices in the UK.

The assessed the effect of exposure to antipsychotic drugs on the likelihood of stroke in 6,790 patients with a recorded incident of stroke and at least one prescription of any antipsychotic between January 1988 and the end of 2002. Of the total cohort, 1,423 patients had recorded dementia during the study period.

The study design was the self-controlled case series method, which is derived from cohort studies and relies on intra-person comparisons in a population of individuals who have both the outcome (i.e., stroke in this case) and exposure (i.e., antipsychotics) of interest.

Rate ratios compare the rate of events during periods of exposure with the rate during all other observed time periods. This removes the potential confounding effect of characteristics that vary between individuals, such as frailty and risk factors for vascular disease, the authors explained.

Presenting their results in the BMJ, they commented: “As the background risk of stroke in elderly patients is relatively high, we re-affirm that the risks associated with antipsychotic drug use in patients with dementia generally outweigh the potential benefits, and use of antipsychotic drugs in these patients should be avoided wherever possible”.

In March 2004, the UK’s Committee on Safety of Medicines (CSM) warned that Eli Lilly’s Zyprexa (olanzapine) and Johnson & Johnson’s Risperdal (risperidone) had been linked to a three-fold increase in stroke when used to treat behavioural problems in older patients with dementia. The CSM recommended against off-label use of the antipsychotics in this setting.

Earlier this year, however, a report published by the All Party Parliamentary Group on Dementia in partnership with the Alzheimer’s Society claimed that as many as 105,000 dementia patients in the UK were being treated inappropriately with antipsychotic drugs.