Alzheimer dementia: Starting, stopping drug therapy
ABSTRACT
Alzheimer disease is the most common type of dementia. Two classes of cognition-enhancing drugs are approved to treat the symptoms, and both have provided modest benefit in clinical trials. Psychotropic drugs are sometimes used off-label to treat behavioral symptoms of Alzheimer disease. All these medications should be continuously evaluated for clinical efficacy and, when appropriate, discontinued if the primary benefit—preservation of cognitive and functional status and a reduction in behaviors associated with dementia—is no longer being achieved.
KEY POINTS
- In 2016, an estimated 5.2 million Americans age 65 and older had Alzheimer disease; by 2050, the prevalence is expected to be 13.8 million.
- Cognitive enhancers (cholinesterase inhibitors and an N-methyl-d-aspartate receptor antagonist) have shown modest efficacy in preserving cognitive function.
- When evaluating therapy with a cognitive enhancer, practitioners need to consider the potential adverse effects, especially gastrointestinal effects with cholinesterase inhibitors.
- Discontinuation should be considered when the dementia reaches the advanced stage and the initial intended purpose of these drugs is no longer achievable.
CONSIDERATIONS FOR OTHER DEMENTIA THERAPY
Behavioral and psychiatric problems often accompany dementia; however, no drugs are approved to treat these symptoms in patients with Alzheimer disease. Nonpharmacologic interventions are recommended as the initial treatment.29 Some practitioners prescribe psychotropic drugs off-label for Alzheimer disease, but most clinical trials have not found these therapies to be very effective for psychiatric symptoms associated with Alzheimer disease.30,31
Recently, a randomized controlled trial of dextromethorphan-quinidine showed mild reduction in agitation in patients with Alzheimer disease, but there were significant increases in falls, dizziness, and diarrhea.32
Patients prescribed medications for behavioral and psychological symptoms of dementia should be assessed every 3 to 6 months to determine if the medications have been effective in reducing the symptoms they were meant to reduce. If there has been no clear reduction in the target behaviors, a trial off the drug should be initiated, with careful monitoring to see if the target behavior changes. Dementia-related behaviors may worsen off the medication, but a lower dose may be found to be as effective as a higher dose. As dementia advances, behaviors initially encountered during one stage may diminish or abate.
In a long-term care setting, a gradual dose-reduction trial of psychotropic medications should be conducted every year to determine if the medications are still necessary.33 This should be considered during routine management and follow-up of patients with dementia-associated behavioral problems.
REASONABLE TO TRY
Cognitive enhancers have been around for more than 10 years and are reasonable to try in patients with Alzheimer disease. All the available drugs are FDA-approved for reducing dementia symptoms associated with mild to moderate Alzheimer disease; donepezil and memantine are also approved for severe Alzheimer disease, either in combination or as monotherapy.
When selecting a cognitive enhancer, practitioners need to consider the potential for adverse effects. And if a cholinesterase inhibitor is prescribed, it is important to periodically assess for perceived cognitive benefits and adverse gastrointestinal effects. The NMDA receptor antagonist has a more favorable side effect profile. Combining the drugs is also an option.
Similarly, patients prescribed psychotropic medications for behavioral problems related to dementia should be reassessed to determine if the dose could be reduced or eliminated, particularly if targeted behaviors have not responded to the treatment or the dementia has advanced.
For patients on cognitive enhancers, discontinuation should be considered when the dementia advances to the point where the patient is totally dependent for all basic activities of daily living, and the initial intended purpose of these medications—preservation of cognitive and functional status—is no longer achievable.
