Older adults who suffer dementia and take antipsychotic drugs have a slightly higher risk of death than those who aren't prescribed these medications, a large Canadian study suggests.

And the older variety of antipsychotics, known as conventional agents, seem to be associated with a higher risk of death than newer atypical antipsychotics, researchers said in the study of Ontario patients, published Tuesday in the journal Annals of Internal Medicine.

The study builds on previous research that led to warnings in the spring of 2005 from Health Canada and the U.S. Food and Drug Administration on atypical antipsychotics and dementia.

Conventional antipsychotic drugs include chlorpromazine (brand names Largactil and Thorazine) and haloperidol (brand name Haldol). Examples of atypical antipsychotics are olanzapine, risperidone and quetiapine (brand names Zyprexa, Risperdal and Seroquel, respectively).

Lead author Dr. Sudeep Gill, a geriatric specialist and adjunct scientist for the Institute for Clinical Evaluative Sciences, said behavioural symptoms in people with dementia can run a full spectrum. Some people have hallucinations and are very suspicious and paranoid, and those symptoms are "well targeted" by antipsychotics.

But sometimes patients with dementia seem agitated and may articulate that they feel restless.

"Paradoxically these drugs may actually worsen that particular symptom," said Gill, an assistant professor of medicine at Queen's University in Kingston, Ont.

He said it's significant that conventional antipsychotics were associated with an even higher mortality risk than atypicals.

Call to expand warnings

After the warnings of two years ago, he noted that some physicians had switched their patients over from the atypical to conventional drugs.

"We were hoping that at a policy level there might be some interest from the drug regulatory agencies, Health Canada, and its comparative agencies in other countries, to look at maybe expanding the warning labels that they apply to atypical antipsychotics to the older conventional antipsychotics," he said.

A statement from Health Canada noted that there are no placebo-controlled clinical trial data on relative risks for illness and death in elderly dementia patients treated with conventional antipsychotics.

"Nevertheless, the data do suggest that the risks associated with treating elderly dementia patients with conventional antipsychotics may be similar to those associated with atypical antipsychotics," Renee Bergeron, a spokeswoman for Health Canada, said in an e-mail Monday.

"Health Canada is currently updating the product monographs for all conventional antispychotics to reflect findings from the available data."

Consider non-drug treatments

The study was based on anonymous data from Ontario residents aged 66 and older with dementia 1997 to 2002. The researchers did not have access to causes of death, so they could not determine why it was that people taking the drugs were more likely to die.

But they did find that the risk of death associated with these drugs, either atypicals or conventional agents, emerges within a month and presisted for at least six months, said Gill, who called the small risk clinically important.

The report looked at people both in the community and in long-term care homes, and Gill said the higher risk of death was comparable in both settings.

Antipsychotics are often prescribed to people with schizophrenia, and their use on people with dementia is very common, Gill said. The researchers hope doctors, patients and caregivers will think critically about the benefits and risks of prescribing the drugs and consider alternative non-drug treatments.  

Non-drug treatments that might help include recollection of pleasant events, physical activity, music therapy and behavioural analysis to find out what's going on. For example, a female patient may lash out to express discomfort with a male attendant bathing her, Gill said.

Caregivers may need more training on dealing with the behaviour of someone who might become aggressive because the person doesn't want a bath, such as backing down on requiring the bath at a particular time of day, said Dr. Michael Borrie, chair of the division of geriatric medicine at the University of Western Ontario, and medical director of a dementia special care unit at Parkwood Hospital, in London, Ont.

Dr. David Conn, co-chair of the Canadian Coalition for Seniors' Mental Health, said the organization released guidelines more than a year ago that say atypical antipsychotics should only be used if there's a risk of harm or if there's great suffering or disability caused by the symptoms.