Antipsychotics continue to be prescribed widely to elderly people to control behavioural and psychotic symptoms in a number of diagnoses. The adverse effects of first-generation antipsychotic agents (FGAs; e. g., haloperidol and phenothiazines), particularly cardiovascular events and movement disorders, such as extrapyramidal symptoms (EPS) and tardive dyskinesia, are well known and documented. However, there are concerns about the use of the newer second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine), which were originally promoted as being safer than the FGAs. For example, several health agencies (Health Canada, FDA, EMA) have advised healthcare professionals and the public of the increased risk of cerebrovascular events and death in patients with dementia treated with antipsychotic agents.
The authors of this population based, retrospective cohort study note that risperidone is the only SGA with an official indication for behavioural disturbances of dementia in Canada as well as in Europe and the US. It is also the antipsychotic agent most commonly prescribed to the over-65 age group. In the UK, specifically, risperidone is indicated for: “The short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others.”
The cohort study included all residents of a Canadian province aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007. The primary outcome measure considered was a composite outcome of a diagnosis for a movement disorder, EPS or parkinsonism, and/or a dispensation of antiparkinson drugs at 360 days. Secondary outcomes were the composite outcomes of a diagnosis of movement disorder, EPS or parkinsonism, and/or a dispensation of antiparkinson drugs at 30, 60, 90, and 180 days. After accounting for all exclusion criteria a total of 8,885 individuals were included in the cohort for analysis: 4,242 persons were in the FGA-exposed group and 4,643 in the risperidone-exposed group.
After controlling for potential confounders (demographics, co-morbidity and medication use):
• The primary outcome measure at 360 days was not statistically significant. The adjusted hazard ratio (HR) was 0.75 with the 95% CI crossing 1.00 (0.54–1.05)
• For the secondary outcome measures, the use of risperidone was associated with a lower risk of EPS adverse events at 30, 60, 90, and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22–0.67; 0.45, 95% CI: 0.28–0.73; 0.50, 95% CI: 0.33–0.77; 0.65, 95% CI: 0.45–0.94, respectively).
The following points are noted in the study discussion:
• The interpretation of these results needs to consider the limitations of observational studies based on administrative data. The authors note, however, that a number of steps were taken to account for potential confounding
• Although it is well known that EPS are dose-related and high doses of risperidone are expected to cause movement effects similar to those caused by FGAs, no attempt was made to evaluate the effect of dose on incidence of EPS in this population
Although the authors present a positive conclusion for their study, it should be noted that their conclusion is based on the secondary outcome measures of this observational study.
The Department of Health launched a Dementia Strategy in 2009, which highlighted concerns around the use of antipsychotics for the management of behavioural and psychological symptoms in people with dementia. The MHRA issued advice for healthcare professionals on initiatives to reduce prescribing of antipsychotics for the behavioural and psychological symptoms of dementia.