Three warnings from Health Canada on the risk of death and stroke among seniors taking antipsychotic drugs failed to reduce the prescription rates of those drugs, according to researchers who suggest health warnings are ineffective at protecting patients.

Between October 2002 and June 2005, Health Canada issued three warnings of increased risk of death or stroke in elderly patients with dementia who take atypical antipsychotic drugs.

In the 1990s, antipsychotics such as Zyprexa (olanzapine), Seroquel (quetiapine) and Risperdal (risperidone) were developed for schizophrenia and other psychiatric conditions.

Of the three drugs, only risperidone is approved by Health Canada to treat symptoms of aggression and psychosis in elderly patients with dementia, although doctors may prescribe conventional and atypical antipsychotic drugs off-label for dementia.

"The three warnings about serious adverse events associated with use of atypical antipsychotic agents in elderly people with dementia had a limited effect on the prescription rates of these agents," Dr. Geoffrey Anderson of the department of health policy, management and evaluation at the University of Toronto and his colleagues write in Tuesday's issue of the Canadian Medical Association Journal.

"We also found that the overall rates of use of these drugs actually increased between the first warning in 2002 and the end of our follow-up in 2007.

"This finding highlights the limited impact of warnings and suggests that more effective approaches are needed to protect vulnerable populations from potentially hazardous medications."

There was a small relative decrease in predicted growth of the use of atypical antipsychotic drugs:

• 5.0 per cent after the first warning.
• 4.9 per cent after the second warning.
• 3.2 per cent after the third warning.

The researchers found the overall prescription rate of antipsychotic drugs among patients with dementia increased by 20 per cent, from 1,512 per 100, 000 elderly patients in September 2002, the month before the first warning, to 1,813 per 100 000 in February 2007, 20 months after the last warning.

Info needed on alternatives

A comprehensive, co-ordinated approach between Health Canada, drug manufacturers, private and public drug insurers and physicians is needed, the study's authors say.

In both the antipsychotic case and warnings on use of antidepressants in children, the warnings did not achieve the desired outcome, Dr. Laurence Katz of the University of Manitoba said in a commentary accompanying the study.

The results suggest doctors will return to what they know, despite documented risks, if they are not given other options.

"Health care warnings should provide accurate, explicit and complete information about the risks and efficacy of the identified treatment in addition to providing the same information on alternative treatments," Katz wrote.

For seniors with dementia, alternative drug and behavioral treatments could be considered, although there is limited evidence to support their use, he said.

Katz agreed with the study's authors that to improve drug warnings, Health Canada will likely have to collaborate with the pharmaceutical industry and physicians and will need access to all data — published and unpublished.

The effectiveness of atypical antipsychotics for elderly patients with dementia was not shown in a randomized control trial and consensus meeting on the topic.

But to reach that conclusion, regulatory agencies and authors had to get access to unpublished reports of trials, mostly from pharmaceutical companies, Katz noted.