Antipsychotics for dementia may raise death risk
Atypical antipsychotic drugs used to treat Alzheimer’s disease and other types of dementia for relatively brief periods, less than 8 to 12 weeks, may be associated with a small increased risk of death, according to an analysis of 15 clinical trials.
“These findings emphasize the need to consider changes in some clinical practices,” Dr. Lon S. Schneider and colleagues at the University of Southern California in Los Angeles contend in the Journal of the American Medical Association.
“Antipsychotic drugs have been dispensed fairly frequently to patients with dementia and used for long periods,” they explain. “The established risks for cerebrovascular adverse events together with the present observations suggest that antipsychotic drugs should be used with care in these patients.”
In their analysis, which included 3,353 patients randomly assigned to treatment with an antipsychotic - risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), or aripiprazole (Abilify) - and 1,757 to placebo, the risk of death was 54 percent higher in subjects randomly assigned to an antipsychotic drug.
Alzheimer’s disease (AD), one form of dementia, is a progressive, degenerative brain disease. It impairs memory, thinking, and behavior.
Memory impairment is a necessary feature for the diagnosis of this or any type of dementia. Change in one of the following areas must also be present: language, decision-making ability, judgment, attention, and other areas of mental function and personality.
The rate of progression is different for each person. If AD develops rapidly, it is likely to continue to progress rapidly. If it has been slow to progress, it will likely continue on a slow course.
More information: Alzheimer’s disease
Specifically, there were 118 deaths in antipsychotic-treated and 40 in placebo-treated subjects (3.5 percent vs 2.3 percent).
Sensitivity analyses did not show evidence for different risks associated with individual drugs, severity of illness or specific diagnosis.
According to the investigators, “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 trial results that there is substantial improvement in both drug and placebo groups during the first 1 to 4 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 of a related editorial encourage clinicians caring for patients with dementia who develops psychotic symptoms or aggression to consider causes other than dementia.
There are two types of AD - early onset and late onset. In early onset AD, symptoms first appear before age 60. Early onset AD is much less common, accounting for only 5-10% of cases. However, it tends to progress rapidly.
The cause of AD is not entirely known but is thought to include both genetic and environmental factors. A diagnosis of AD is made based on characteristic symptoms and by excluding other causes of dementia.
Prior theories regarding the accumulation of aluminum, lead, mercury, and other substances in the brain leading to AD have been disproved. The only way to know for certain that someone had AD is by microscopic examination of a sample of brain tissue after death.
More information: Alzheimer’s disease
“Delirium, untreated or undertreated medical illnesses, overmedication, environmental triggers, lack of engaging activities, and misinterpretation of disease symptoms are among the potential (causes) of such behaviors and symptoms,” Dr. Peter V. Rabins and Dr. Constantine G. Lyketsos of Johns Hopkins in Baltimore write.
They also encourage clinicians to consider the risk/benefit ratio of these agents on an individual basis. “For example, patients with hallucinations and delusions that are neither distressing nor placing them or others at risk or harm should not be treated with antipsychotic drugs,” Rabins and Lyketsos suggest.
Once antipsychotic drugs are prescribed, careful follow-up to determine the need for continuing the medication is crucial, they add.
SOURCE: JAMA, October 19, 2005.
Revision date: June 18, 2011
Last revised: by Sebastian Scheller, MD, ScD