Antipsychotics for Dementia Raises Mortality Rate

KINGSTON, Ontario, June 4 -- Using antipsychotic drugs to treat patients with dementia may be fatal, according to researchers here.

They found a sharply increased risk of death that was evident within a month of starting the drugs, reported Sudeep Gill, M.D., of Queen's University and St. Mary's of the Lake Hospital, and colleagues, in the June issue of Annals of Internal Medicine.

The mortality rate was higher with the older "conventional" medications than with the newer "atypical" antipsychotics, Dr. Gill said. "Our study adds to mounting concerns about the use of antipsychotic drugs in dementia."

The finding - from a large population-based cohort study here - reinforces warnings issued two years ago by both the FDA and Health Canada, Dr. Gill and colleagues reported.

On the basis of meta-analyses of randomized controlled trials, both agencies warned of an increased mortality risk when the atypical antipsychotic drugs were used to treatment patients with dementia. But the warnings were based on relatively small trials and did not address the issue of older medications.

The atypical drugs include such medications as olanzapine (Zyprexa) and risperidone (Risperdal), while the conventional drugs include such agents as haloperidol (Haldol) and chlorpromazine (Thorazine).

To fill in the gaps, Dr, Gill and colleagues conducted a retrospective study of 27,259 matched pairs of dementia patients - those treated with antipsychotics at least once and those who were never given the drugs from April 1, 1997 through March 31, 2002.

Patients in the cohort were matched according to whether they lived in the community or in long-term care facilities and whether they had atypical or older antipsychotic medications, Dr. Gill and colleagues said.

Data were derived from four administrative health care databases in Ontario, including pharmacy, hospitalization, physician billing and outpatient services records.

The researchers used the method of propensity score matching to ensure that the cohorts were well matched and to account for most possible confounding factors.

Analysis found:

• New use of atypical antipsychotics in the community was associated with a 31% increase in the risk of all-cause mortality 30 days after starting the prescription, compared to dementia patients not using the drugs. The hazard ratio was 1.31, with a 95% confidence interval from 1.02 to 1.70.

• New use of atypical antipsychotics in long-term care facilities was associated with a 55% increase in the risk of all-cause mortality, compared to dementia patients not using the drugs. The hazard ratio was 1.55, with a 95% confidence interval from 1.15 to 2.07.

When the older drugs were compared to the atypical medications, the 30-day mortality risk was even greater. In the community, the hazard ratio was 1.55 (with a 95% confidence interval from 1.19 to 2.02) while in the long-term care facilities it was 1.26 (with a 95% confidence interval from 1.04 to 1.53).

"The clinical message is that even short-term use of these drugs can be associated with an increased risk of death," Dr. Gill said. "Physicians need to carefully weigh potential risks and benefits of using these drugs to manage symptoms of dementia, and they need to reassess the use soon after they're initiated to see if they can be safely discontinued."

While the antipsychotics may benefit some patients, "they are not appropriate for everyday use for everyone with dementia," he said.

But, he added, "this study shouldn't lead to a panic about these drugs. The risk for an individual patient is relatively small. But our results are clinically important."

The researchers noted that the study was limited by its design and may be unable to account for all possible confounding factors.

Additional source:

Annals of Internal Medicine

Source reference: Gill SS et al. "Antipsychotic Drug Use and Mortality in Older Adults with Dementia."

Ann Intern Med

2007;146:775-786.