Many Alzheimer's patients get drugs with opposing effects, study finds

"Cholinesterase inhibitors are today's primary therapy for slowing Alzheimer's disease," said study leader Denise Boudreau, PhD, RPh, an associate scientific investigator at Group Health Research Institute. "Anticholinergic properties are often found in drugs commonly used to treat gastrointestinal disorders, allergies, urinary incontinence, depression, and Parkinson's disease, and they can have negative effects on cognition and function in the elderly. There's concern that if someone is taking both types of drugs -- cholinesterase inhibitors and anticholinergic medications -- they will antagonize each other, and neither will work."

In clinical trials, cholinesterase inhibitors show modest effects against the functional and cognitive decline of people with Alzheimer's disease. These medications, such as donepezil (Aricept) work by inhibiting the breakdown of acetylcholine, which sends signals in the nervous system. By contrast, anticholinergics -- such as diphenhydramine (Benadryl) and oxybutynin (Ditopan) -- block the action of acetylcholine. Since the two types of drugs have opposite effects, it makes sense not to give both kinds of drugs to an individual person. But until Dr. Boudreau's study, few researchers had explored how often patients are prescribed both types of medications and which harms this might cause.

Dr. Boudreau and colleagues conducted a retrospective cohort study of 5,625 people aged 50 or older who received a new prescription for cholinesterase inhibitors between 2000 and 2007. The researchers used electronic pharmacy records of Group Health Cooperative and Kaiser Permanente Colorado, nonprofit health care systems that together provide care to more than a million people. The research team found patients who also had a prescription for anticholinergics from the year before their cholinesterase prescription until the analysis ended on December 31, 2008, or the patient left the health care system or died. The study was the first to use state death records and insurance claims for nursing home care to look for effects of taking both drug types.

The researchers found:

• Of the cholinesterase inhibitor users, 37 percent were also taking at least one anticholinergic drug, and more than 11 percent took two or more. This was similar to other studies of Medicare beneficiaries.
• For those using both medication types, dual use generally lasted three to four months, but 25 percent used both classes of drugs for more than a year.
• Anticholinergics were already being used in 23 percent of people receiving a new cholinesterase inhibitor prescription, and 77 percent continued, even after starting the cholinesterase inhibitor.
• Subjects using both medication types were not more likely to enter a nursing home or to die than those taking only cholinesterase inhibitors.

"It's reassuring that we did not observe an association between simultaneous use of the two types of drugs and increased risk of death or nursing home placement," said Dr. Boudreau. "But concomitant use of these drugs is, at the very least, not optimal clinical practice." Preventing concurrent use of opposing drugs could also be a chance to reduce waste in health care spending, since a month of donepezil treatment costs approximately $180.

One reason that health care providers might prescribe conflicting medications is that dementia patients often have multiple medical conditions. Also, anticholinergics are often given to counteract the side effects of cholinesterase inhibitors, which are one of the few available treatments for people with Alzheimer's. Dr. Boudreau hopes the study raises awareness about the potential inappropriateness of prescribing both types of drugs -- and stimulate discussions about the best way to make therapeutic decisions for people with Alzheimer's.

"Providers, families, and patients should carefully consider the extent to which demonstrated benefits or harms in an individual patient justify long-term use of these drugs," said Dr. Boudreau. "A good first step is to have clearly agreed-upon goals for therapy and a plan to monitor for effects and side effects." Now Group Health Research Institute scientists have started to work with Group Health Cooperative on steps like these to improve the quality of care.

A contract with the National Heart, Lung, and Blood Institute supported this research.

Dr. Boudreau's co-authors are Senior Biostatistician Onchee Yu, MS, Group Health Vice President for Research and Executive Director Eric B. Larson, MD, MPH, and Jeanene Johnson, MPH, of Group Health Research Institute, in Seattle; Shelly L. Gray, PharmD, MS, of the University of Washington; and Marsha A. Raebel, PharmD, of the Kaiser Permanente Colorado Institute for Health Research and the University of Colorado at Denver. Drs. Boudreau and Larson are also affiliated with the University of Washington.