The novel antipsychotic drugs olanzapine (Zyprexa®) and risperidone (Risperdal®)
Dementia involves progressive loss of intellectual abilities such as language, comprehension, memory and learning, as well as changes in behaviour. This report focuses on agitation (restless movement with feelings of tension and irritability) occurring in those diagnosed with dementia.
Novel antipsychotics are a new generation of drugs developed to overcome the significant side effects associated with conventional antipsychotic drugs. Antipsychotic drugs may be used to treat dementia-associated agitation, typically after or in combination with environmental or behavioral changes. The novel antipsychotics clozapine, olanzapine, risperidone and quetiapine are available in Canada. Of these, only risperidone is approved for the treatment of behavioural disturbances in patients with dementia.
DAA causes stress for caregivers and affects quality of life for patients. Conventional antipsychotic drugs have a number of significant side effects, such as extrapyramidal symptoms. Although the efficacy and safety of novel antipsychotic drugs may not be clear for all conditions, the number of prescriptions and indications for the use of novel antipsychotics continue to increase.
This assessment critically examines the evidence on the efficacy and safety of novel antipsychotics as compared to placebo and as compared to conventional antipsychotics, for the management of patients with DAA.
Published and grey literature were systematically searched. All relevant trials enrolling patients with DAA were included. A total of seven randomized controlled trials reporting on olanzapine and risperidone met the inclusion criteria for the review.
- The efficacy of intramuscular olanzapine for the rapid treatment of DAA was found to be comparable to that of lorazepam (a benzodiazepine), and better than that of placebo, for institutionalized elderly patients. Adverse events at 24 hours were the same for all three patient groups.
- Over the longer term (6 to 12 weeks), the evidence regarding the efficacy, measured using behavioural scales in elderly patients, of olanzapine and risperidone compared to placebo was variable: some trials showed benefit and some did not. Both drugs increased some types of side effects.
- In two 12-week trials in elderly patients with DAA, risperidone was compared to the conventional antipsychotic agent haloperidol. Efficacy was similar with both drugs. However, haloperidol increased the incidence of extrapyramidal symptoms significantly.
- DAA is a long-term condition often requiring treatment for years, yet trials have been relatively short (6 to 12 weeks).
- Health Canada has recently advised that elderly dementia patients on risperidone may have an increased risk of cerebrovascular adverse events.
- Novel antipsychotics are expensive drugs, relative to more established alternatives. Cost-effectiveness analyses may clarify relative costs and benefits.