A newer class of antipsychotic drugs is being prescribed with increasing frequency to older adults to manage agitation associated with dementia.
But a new study in the British Medical Journal has found that few randomized trials have evaluated these newer drugs in the management of behavioural and psychological symptoms (BPSD) of dementia. Although there is a perception of efficacy and improved adverse event profiles compared with typical antipsychotic drugs, this view is based on limited evidence.
Led by Baycrest Centre for Geriatric Care, the study is published in the July 10 issue of the BMJ.
Dr. Paula Rochon, Baycrest geriatrician and scientist, is senior author of the BMJ study. She is highly regarded for her research and advocacy in the area of improved prescribing practices for seniors. Dr. Rochon and colleagues from the BMJ study published another study – in the May 4, 2004 issue of the Journal of the American Geriatrics Society – that found a remarkable one quarter of Ontario seniors are managed with antipsychotic drugs within a year of admission to a long term care facility.
“Not only do we need to review how these therapies are being used in institutions, but we need to study atypical antipsychotic drugs more rigorously in the older population to be absolutely sure the benefits outweigh any harmful risks,” says Dr. Rochon.
Baycrest investigators conducted a systematic review of published clinical trial literature internationally, looking for double blind, randomized control trials of commonly used oral atypical antipsychotic drugs Ð such as risperidone, olanzapine and quetiapine. These drugs were introduced in the 1990s and have been promoted as having similar benefits as older typical neuroleptic agents, with fewer side effects. Randomized control trials (RCTs) are considered the gold standard in measuring a drug’s efficacy.
Only five RCTs, with a combined total of 1,570 patients, were identified. All five trials were sponsored by the pharmaceutical industry. These trials looked at risperidone or olanzapine, and no other atypical drugs.
Investigators found that efficacy evidence was variable; some trials showed benefit in their primary outcome measure and some did not. The trials were of short duration (six to 12 weeks) despite the fact that in clinical practice patients with BPSD are sometimes maintained on antipsychotic treatment for months or years. Most trials reported high withdrawal rates in the treatment and placebo groups. In two trials, half of the withdrawals were due to adverse events such as antipsychotic-induced parkinsonism, drowsiness and abnormal gait. None of the atypical drugs were compared to each other.
“Given that patients with dementia who experience BPSD are commonly treated with the newer class of antipsychotics, our study highlights the surprisingly few well-designed trials that evaluate their use in this population,” says behavioral neurology fellow and geriatrician Dr. Philip E. Lee, who co-authored the study with Dr. Rochon.
“We would urge that further investigation and evaluation of the drugs’ safety and efficacy in elderly patients be performed.”
There is increasing concern that treatment with atypical antipsychotics may be associated with other adverse events, such as impaired glucose metabolism (that can lead to diabetes). More recently, there has been concern about the risk of cerebrovascular events.
The study team included Drs. Paula Rochon, Philip E. Lee, Morris Freedman, Sudeep Gill and doctoral candidate Michael Hillmer.
Funding for the study was provided by the Canadian Institutes of Health Research.