Mortality Risk in Elderly Dementia Patients May Rise With Newer Anti Psychotics

Elderly patients with dementia who take so-called atypical anti-psychotic drugs have an increased risk of death, according to a meta-analysis of clinical trials.

The increased risk of about 50% compared with placebo was not found for any individual drug and could not have been detected by any of the individual trials included in the analysis, according to a report published in the Oct. 19 issue of the Journal of the American Medical Association.

“It is only when all trials are combined that a statistically significant effect is found,” said Lon S. Schneider, M.D., and colleagues at the University of Southern California, Los Angeles.

During the past decade, the atypical antipsychotics have largely replaced conventional antipsychotics such as Haldol (haloperidol) and Mellaril (thioridazine). They are used to treat delusions, aggression, and agitation in patients with Alzheimer’s and other dementia.

However, there has been concern about a possible increased risk of cerebrovascular events and mortality associated with the use of atypical antipsychotics. Atypical antipsychotic drugs include Risperdal (risperidone), Zyprexa (olanzapine), Seroquel (quetiapine), and Abilify (aripiprazole).

The meta-analysis included 15 randomized, placebo-controlled trials (nine unpublished) of eight to 12 weeks’ duration. Sixteen different antipsychotic drugs were covered. The trials included 3,353 patients randomized to treatment groups and 1,757 to placebo. Patient age averaged 77 to nearly 84, depending on the trial.

Death occurred more often in patients randomized to drugs (118 or 3.5%) than placebo (40 or 2.3%). The odds ratio for increased mortality risk was 1.54 (95% confidence interval=1.06-2.23; P=.02).

Sensitivity analyses did not find differential risks associated with individual drugs, diagnosis, or disease severity.

The researchers speculated that elderly patients with dementia, who are often frail and ill with comorbid conditions, may be at increased mortality risk when given a wide variety of drugs, including not only antipsychotics but antidepressants, sedatives, hypnotics, anticonvulsants, and antihypertensive drugs. The increased mortality risk may also be associated with conventional antipsychotics, they said.

“These findings emphasize the need to consider certain changes in some clinical practices,” the study authors wrote.

“The fact that excess deaths and cerebrovascular adverse events can be observed within 10 to 12 weeks of initiating medication, coupled with observations from individual clinical trials results that there is substantial improvement in both drug and placebo groups during the first one to four weeks of treatment, lead to the consideration that antipsychotic drugs should be prescribed and dosage adjusted with the expectation of clinical improvement within that time,” the authors said. “If improvement is not observed, the medication could be discontinued.”

Dr. Schneider has served as a consultant to AstraZeneca, Eli Lilly, Bristol-Myers Squibb, Johnson & Johnson, Novartis, and Pfizer, all manufacturers of antipsychotic medications.

Print Version
Tell-a-Friend