Author(s): Laura J Morrison MD and Solomon Liao MD
Background In the past ten years new drugs have been marketed to delay the progression of dementia. No studies have addressed when or if these drugs should be stopped as cognitive and functional decline progress. Palliative care professionals are frequently asked about the continued role of these drugs in the face of functional decline and short prognosis. This Fast Fact will suggest guidelines for continued use or discontinuation in the hospice/palliative care setting.
Cholinesterase Inhibitors (ChEIs): e.g. galantamine, donepezil, rivastigmine
Indication: mild to moderate dementia—usually started as first line agents. Evidence: A 2005 meta-analysis has called into question the degree of benefit, if any, of ChEIs even in mild to moderate dementia (1), and expert opinions vary widely on the clinical significance of reported positive outcomes from earlier studies on ChEIs. Few studies have looked at efficacy in moderate to severe dementia. Some studies have suggested ChEIs have a role in controlling behavior problems (2) and lessening opioid related somnolence (3). One study suggested a potential precipitous cognitive decline if ChEIs are stopped suddenly (4). Cost: ~$129-135/month (average wholesale price). Side Effects: diarrhea, nausea, anorexia, insomnia, bradycardia.
N-methyl-D-aspartate (NMDA) receptor antagonist: memantine.
Indication: moderate to severe dementia. Evidence: Studies suggest a modest beneficial effect with decreased cognitive and functional decline in patients with moderate to severe dementia. Again, the clinical significance for patients is debated. Cost: $136/month at 10mg twice daily (average wholesale price). Side Effects: dizziness, headache, constipation.
Use a shared decision-making model with patients/surrogates guided by the goals of care (e.g. life prolongation and/or symptom relief), carefully weighing the expected benefits and burdens (see reference 5 for specific guidance on medication appropriateness late in life). Be prepared to make a clear recommendation based on best available evidence. Due to the advanced status of many dementia patients entering hospice or being seen by palliative care programs, it’s reasonable to recommend stopping ChEIs and memantine, as the evidence for their benefit is marginal at best. These medications may be viewed as prolonging a poor quality of life and/or the process of dying.
If there is uncertainty, consider a time-limited trial of medication continuation or discontinuation, with serial reassessment of target cognitive or behavioral indicators. Families should be made aware that a decline following discontinuation may not be reversible.
In the case of a patient with dementia-related behavior problems, clinicians or family may feel that medications play an important role in lessening the behaviors; continuing medications may be reasonable. Alternatively, using non-pharmacologic strategies and/or increasing or starting an antipsychotic can often help control behavior problems without the use of ChEls or memantine.
When the decision is made to stop a medication, common geriatrics wisdom supports a gradual dose taper rather than abrupt discontinuation.
Clinicians should inform all involved healthcare team members of a recommendation to discontinue medication along with the rationale for discontinuation (6).
Working with Families The reaction of families to a discussion of discontinuing these drugs is often emotional and may be a source of tension between family members. Some will view these medications as a final hope for prolonged life or improved function and will resist discontinuation. For others, permission to let go, to accept impending death and remove a perceived burden of cost and daily pill taking, will be welcomed. Clinicians can best help families by focusing discussion around the overall goals of care (see Fast Facts #29, 65).
Kaduszkiewicz H, Zimmerman T, Beck-Bornholdt H-P, van den Bussche H. Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomized clinical trials. BMJ. 2005; 331:321-27.
Wynn ZJ, Cummings JL. Cholinesterase inhibitor therapies and neuropsychiatric manifestations of Alzheimer's disease. Dement Geriatr Cogn Disord. 2004; 17(1-2):100-8.
Slatkin NE, Rhiner M. Treatment of opiate-related sedation: utility of the cholinesterase inhibitors. J Support Oncol. 2003; 1(1):53-63.
Minett TS, Thomas A, Wilkinson LM, Daniel SL, Sanders J. Richardson J, Littlewood E, Myint P, Newby J, McKeith IG. What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson’s disease with dementia. Int J Geriatr Psychiatry. 2003; 18(11):988-93.
Holmes HM, Hayley DC, Alexander GC, Sachs GA. Reconsidering medication appropriateness for patients late in life. Arch Intern Med. 2006;166(6):605-9.
Gwyther LP, Weinberg AD. Discontinuing medications for a resident with advanced Alzheimer’s disease. Ann Long-Term Care. 2006:14(5):46-8.
Fast Facts and Concepts are edited by Drew A Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: firstname.lastname@example.org. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu.
Version History: This Fast Fact was originally edited by David E Weissman MD and published in February 2007. Current version re-copy-edited in April 2009.
Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Morrison LF, Liao S. Dementia Medications in Palliative Care. Fast Facts and Concepts. February 2007; 174. Available at: http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_174.htm.
Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.
ACGME Competencies: Patient Care, Interpersonal and Communication Skills
Keyword(s): Non-Pain Symptoms and Syndromes