A new study is set to examine how two drugs commonly used in dementia treatment may lead to a cascade of side effects when taken together.

Cholinesterase inhibitors (ChEIs) such as donepezil are a first-line treatment for confusion in dementia. The drugs often trigger urinary incontinence, which in turn is treated with antimuscarinics such as oxybutynin. Taken together, the two drug classes may set off a series of side effects that require additional drug treatment, said lead researcher Rajender Aparasu, MPharm, Ph.D., from the University of Houston.

With a grant from the National Institute of Aging, Aparasu’s team will analyze health records from four million Medicare beneficiaries over the age of 65 in whom Alzheimer’s has been diagnosed, to examine how the medications interact. “[Our aim is] to assess all severe adverse effects associated with ChEI-antimuscarinic interaction in older adults with the disease,” Aparasu said.

“With a cascading effect, basically it is the medication that is making you worse rather than the disease,” said Aparasu. “[T]he combination of the two drugs worsens the dementia in patients, causing them to have behavioral issues, which is why they end up on memantine [which treats severe confusion] and antipsychotic medications, which may lead to even more severe adverse events,” he said. 

In earlier research, the study team found that cascading side effects from ChEI use led to 30% of patients being prescribed memantine and 23% being prescribed antipsychotics.