VANCOUVER—Medications can help manage symptoms and prolong function in patients with dementia, even if the effects are modest and do not affect the underlying disease, according to an overview of dementia management provided at the 68th Annual Meeting of the American Academy of Neurology. Neurologists should bear in mind drug indications and patient diagnoses because certain drugs are indicated for Alzheimer’s disease dementia only, and it is unclear if they provide benefit in other forms of dementia.
Psychotropic medications also may play a role in treating behavioral and psychiatric symptoms, although it is important to first identify underlying causes that could trigger these symptoms, said Gregory S. Day, MD, MSc, Instructor in Neurology at Washington University in St. Louis.
Gregory S. Day, MD, MSc
Two Drug Types
Two types of medications are FDA-approved for the treatment of dementia: acetylcholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and memantine, a partial NMDA-receptor antagonist. The FDA first approved an acetylcholinesterase inhibitor to treat dementia in 1993. Memantine was approved in 2003.
More recently, new formulations and dosages of those four drugs have been approved by the FDA, including a rivastigmine transdermal patch, a once-daily dose of memantine, and a donepezil and memantine combination pill.
Each medication requires a dose titration schedule. Donepezil is taken once daily; rivastigmine, galantamine, and memantine have once- and twice-daily formulations.
The acetylcholinesterase inhibitors are approved for the treatment of dementia due to Alzheimer’s disease. Rivastigmine also is FDA-approved for Parkinson’s disease dementia. Each drug also is used off label for the treatment of other forms of dementia, particularly dementia with Lewy bodies, Parkinson’s disease dementia, and vascular dementia, although it is unclear if off-label use in other forms of dementia provides benefit, Dr. Day said.
Donepezil and rivastigmine are approved for all stages of dementia, whereas galantamine is not approved for severe dementia because a controlled trial was never conducted in that patient population. A systematic review found no measurable effect of acetylcholinesterase inhibitors in patients with undifferentiated mild cognitive impairment.
In clinical trials, individuals with mild to moderate dementia due to Alzheimer’s disease taking acetylcholinesterase inhibitors had a modest benefit in function and cognition, compared with those taking placebo. “That benefit is relatively sustained throughout the course of the trial, but it is modest at best,” he said.
Adverse Events
Side effects of acetylcholinesterase inhibitors occur in 10% to 20% of patients. Gastrointestinal side effects (eg, nausea, vomiting, diarrhea, or anorexia) are the most common. Starting patients at a lower dose, varying the time of day the medication is taken, and taking the medication with food may alleviate some of these symptoms. Side effects may subside after one or two weeks, so it may be worth continuing the medication if the side effects are not severe, Dr. Day said.
Serious side effects can include syncope, convulsive seizures, loss of consciousness, and rhabdomyolysis. Less common side effects can include changes in cognitive or psychiatric comportment and cardiac complications. Rivastigmine in the transdermal formulation has an additional caveat because the patches can cause hypersensitivity reactions on the skin.
A 2015 review of drug prescribing records in North America found an increased risk of death in individuals taking acetylcholinesterase inhibitors. “Digging a little deeper, we see that this risk is almost entirely accounted for by rivastigmine,” Dr. Day said. “If anything, we could argue that people prescribed donepezil and galantamine have a lower risk of death than those not on these medications.”
Various factors could account for the elevated risk with rivastigmine. The drug has a slightly different mechanism of action and a longer half-life. Perhaps more importantly, as the only medication that can be delivered via transdermal patch, it may be prescribed to people with more severe forms of dementia who are no longer able to take medications by mouth, or who have agitation or psychoses. In addition, patients may forget to remove a patch and end up wearing multiple patches. Finally, rivastigmine is FDA-approved for Parkinson’s disease dementia, and the risk of death may be higher in those patients, Dr. Day said.
Memantine Alone and in Combination
Memantine is FDA-approved for patients with moderate to severe dementia due to Alzheimer’s disease. Pooled data indicate a small beneficial effect on cognition, activities of daily living, and behavior in this population. Despite multiple trials, there is no evidence of benefit of memantine in patients with mild dementia due to Alzheimer’s disease, and there is no convincing evidence to support the use of memantine in other forms of dementia.