Examining the side effects of Alzheimer’s disease dementia drugs

In a first of its kind study, a University of Houston researcher is examining two common drugs used for dementia in patients with Alzheimer’s disease to determine the extent to which they don’t mix well together and cause a cascading event of side effects, prompting the need for even more medications. The medications are cholinesterase inhibitors (ChEIs) like donepezil, which curbs dementia symptoms and antimuscarinics like oxybutynin, which treats urinary incontinence, often caused by taking the ChEIs.

“With a cascading effect, basically it is the medication that is making you worse rather than the disease,” said Rajender Aparasu, professor and chair of the Department of Pharmaceutical Health Outcomes & Policy at the University of Houston College of Pharmacy, who has been awarded $450,000 by the National Institute of Aging to investigate the adverse effects of mixing cholinesterase inhibitors and antimuscarinics in older adults with Alzheimer’s disease.

For patients with dementia caused by Alzheimer’s disease, the first line treatment is a cholinesterase inhibitor. While they have moderate success in curbing dementia symptoms, they often lead to the use of antimuscarinics to treat overactive bladder symptoms. This begins a cascade of events that often causes other symptoms which must be medicated with other drugs, including antipsychotics to treat behavioral symptoms like agitation, delusions and hallucinations.

“What is happening is the combination of the two drugs worsens the dementia in patients, causing them to have behavioral issues, which is why they end up on antipsychotic medications, which may lead to even more severe adverse events,” said Aparasu, referring to the FDA’s black box warning on antipsychotics which cautions that the medications can increase the risk of death in dementia patients. Many patients with worsening dementia also end up taking the drug memantine. Preliminary research by Aparasu’s research team found memantine and antipsychotics were initiated by 30% and 23% of Alzheimer’s patients, respectively, after the initial cascade. Alzheimer’s disease accounts for 50% to 60% of dementia cases and nearly half of dementia-related deaths.

Aparasu will examine the records of over four million adults on Medicare, over the age of 65, who suffer from Alzheimer’s disease.

“Our aim is to examine the extent of prescribing cascades of ChEIs in older adults with Alzheimer’s disease and to assess all severe adverse effects associated with ChEI-antimuscarinic interaction in older adults with the disease,” said Aparasu. The research will help to reduce drug interactions and their adverse effects in dementia.

“The goal is to evaluate the drug interactions and their adverse effects so we can come up with information which practitioners can use to improve quality of medication use in dementia,” he said.

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