Risky in Alzheimer’s: Zyprexa, Risperdal, Seroquel

The anti-psychotic drugs Zyprexa (olanzapine), Risperdal (risperidone) and Seroquel (quetiapine) do not offer people with Alzheimer’s disease significant relief from symptoms of delusion and aggression, according to a new study. Moreover, the drugs carry risks of sudden death and other side effects that may offset any benefit within this patient population. The Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer’s Disease (CATIE-AD) trial was the first major study of its kind to include people with Alzheimer’s living outside a nursing home. Results were reported in The New England Journal of Medicine (NEJM) and summarized by the Associated Press (AP) on October 12. Among the approximately 4.5 million Americans diagnosed with Alzheimer’s disease, approximately 75% will develop aggressive behavior, delusions or hallucinations, according to the AP report, and consequently may try to harm their caregivers or themselves – often prompting a move to a nursing home. About 25% of people in nursing homes are on drugs such as Zyprexa, Risperdal or Seroquel, according to the AP, and roughly an equal number of people with Alzheimer’s living at home have also taken them – despite very limited evidence of benefit. Unfortunately, no alternative drugs currently exist, and better medications will not be approved for some years. The 42-site, placebo-controlled study by Lon S Schneider, MD, and colleagues involved 421 people with Alzheimer’s disease and psychosis who were living at home (or with a relative or in an assisted-living situation) and required a high level of care. All participants received either olanzapine (mean 5.5 mg daily), quetiapine (mean 56.5 mg daily), risperidone (mean 1.0 mg daily) or placebo. All of the active drugs are newer-generation anti-psychotics developed to treat schizophrenia. However, they may be prescribed off-label by doctors for other indications, and all carry warnings that they raise the risk of death for elderly people with dementia-related psychotic symptoms and are not approved for use in these patients. Researchers followed participants for 36 weeks – a longer time-period than in prior studies – and doses were adjusted as needed. Results showed symptom improvement in about 30% of participants receiving active drugs, and in about 21% of participants on placebo. Some participants switched treatments during the study’s second phase (results of which are scheduled for release in spring 2007). Although the rate of death was higher in the group taking active medication (5 versus 2 deaths), the researchers noted that this difference may purely have been due to chance, and they did not report the causes of death. The study’s lead investigator, Dr Schneider, director of the Alzheimer’s Disease Center of California and a University of Southern California professor, noted that doctors should try using the anti-psychotic drugs on patients as needed, but recommended that they be closely monitored for both improvement and side effects: “Patients are put on these kinds of medications and not particularly monitored and treated for indefinite periods of time,” Schneider reportedly said. “That just maximizes risk.” He added that, while people with Alzheimer’s in nursing homes need symptom relief more because they generally have worse behavior problems, their health tends to be more fragile and they are therefore more vulnerable to developing side effects. In an editorial appearing in the same issue of the NEJM, Dr Jason Karlawish of the University of Pennsylvania’s Alzheimer’s Disease Center wrote that Zyprexa, Risperdal and Seroquel offered benefits to some people with Alzheimer’s, with few or no side effects. However, he noted that the study suggest that Zyprexa and Risperdal are equally effective and superior to placebo and Seroquel in treating behavioral problems related to Alzheimer’s, “but this benefit was limited to a subgroup of patients who either tolerated or did not have side effects such as parkinsonism and sedation… “These results …suggest that these drugs have a limited, but at times necessary, role in the care of patients with Alzheimer’s disease.”