Saturday, November 16, 2013

Drug Treatments and Dementia

Cholinesterase inhibitors (ChEIs) are the most common medications used for the treatment of symptoms of Alzheimer disease (AD). Although not recommended for the treatment of vascular dementia (VD), standard recommendations for AD often include a trial of treatment with ChEIs with discontinuation of drug therapy in non-responding patients.

Currently, three ChEIs are prescribed in Canada: donepezil (Aricept), galantamine (Reminyl), and rivastigmine (Exelon). The benefits of cholinesterase inhibitors for people with AD are generally small. The drugs do not reverse the effects of dementia. However, research suggests that in about half of patients, the drugs delay the worsening of cognitive decline for between six months to a year. A minority of patients may benefit more. Side effects of ChEIs include nausea, vomiting, diarrhea, anorexia, weight loss, dizziness, bradycardia (heart rate of under 60 BPM), myalgias (muscle pain), and insomnia.

It appears that the cardiovascular toxicity of ChEIs is underappreciated by physicians. At St. Michael’s hospital in Toronto, the health records of elderly patients were examined. Researchers concluded that ChEI therapy more than doubles the risk of hospitalization for bradycardia.  Of the ChEI-bradycardia patients studied, 11% required a pacemaker and 4% died before discharge. Findings showed that among those patients discharged from hospital more than half resumed ChEI therapy.

Non-drug therapies for dementia include cognitive-behavioural interventions, validation therapy, multisensory therapies such as music and art therapy, and others. Studies of non-drug therapies for dementia have been shown to delay cognitive decline without adverse side-effects, with studies yielding effect sizes similar to those of ChEIs. These therapies have also been shown to a) enhance the ability of AD patients to carry out activities of daily living (housekeeping, meal preparation, eating, personal hygiene, dressing etc.), and b) enhance the quality of life for both patient and their primary caregiver. Data show that day-to-day functioning and quality of life are not enhanced by ChEI medication. 

Increasingly, second-generation antipsychotic medications (or atypical antipsychotics), (originally developed to treat schizophrenia and other psychoses, have been used in AD to stabilize mood and reduce anxiety, tension, and hyperactivity, and control agitation and aggressiveness. Increased use of these drugs has continued despite the known side-effects and risks, including sedation, higher risks of falls and hip fractures, tardive dyskinesia (Parkinson's disease-type symptoms), cardiovascular events (stroke and heart attack), and overall greater risk of death. In response, Health Canada issued a warning in June, 2005:
"…treatment with atypical antipsychotic medication of behavioral disorders in elderly patients is associated with an increased risk for all-cause mortality. Except for risperidone (RISPERDAL), these medications are not approved for use in elderly patients with dementia."
In 2007, the BC Clinical Practice Guideline on Cognitive Impairment in the Elderly recommended environmental, behavioural, and psychosocial interventions as the first line of treatment for behavioural and psychological symptoms of dementia. The Guideline also recommended that physicians exercise caution when prescribing antipsychotic medications for elderly persons with dementia due to their side effects and the increased risk of death. Yet data collected in British Columbia between April 2010 and June 2011 showed that 50.3 percent of residential care patients were prescribed an antipsychotic. The data included 477,765 prescriptions dispensed at a cost of $9.245 million.

Earlier this month, the pharmaceutical company Johnson & Johnson agreed to pay over $2.2 billion to resolve allegations that the company downplayed known side-effects of Risperdal and aggressively marketed its use for seniors, children and the disabled. Other drugs companies have also agreed to pay billions of dollars in response to similar allegations regarding other atypical antipsychotics. A class action suit against Johnson & Johnson is currently underway in Canada (see http://risperdalcanadaclassaction.com/).

References

British Columbia Ministry of Health. (2011). A review of the use of antipsychotic drugs in British Columbia residential care facilities. Retrieved from http://www.health.gov.bc.ca/library/publications/year/2011/use-of-antipsychotic-drugs.pdf

Globe and Mail (November 2013). Johnson & Johnson to pay $2.2-billion to settle U.S. drug probes. Retrieved from http://www.theglobeandmail.com/report-on-business/international-business/us-business/johnson-johnson-settles-suit-over-marketing-unapproved-drugs/article15242384/

Graessel1, E., Stemmer, R., Eichenseer, B., Pickel1, S., Donath, Kornhuber, J., & Luttenberger, K. (2011).  Non-pharmacological, multicomponent group therapy in patients with degenerative dementia: A 12-month randomized, controlled trial. BMC Medicine (9)129. Retrieved from http://www.biomedcentral.com/content/pdf/1741-7015-9-129.pdf

Hagen. B., Armstrong Esther, C., Ikuta, R., Williams, R. J., Le Navenec, C., & Aho, M. (2005). Antipsychotic drug use in Canadian long-term care facilities: prevalence, patterns following resident relocation. International Psychogeriatrics, 17(2). Retrieved from https://www.uleth.ca/dspace/bitstream/handle/10133/378/Antipsychotic_drug_use.pdf%3Fsequence%3D1

Health Canada (2005). Health Canada endorsed important safety information on atypical antipsychotic drugs and dementia. Retrieved from http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2005/14307a-eng.php

Lee, P.E., Hsiung, G. R., Seitz, D., Gill, S. S., & Rochon, P. A. (2011) Cholinesterase inhibitors. BCMJ 53(8). Retrieved from http://www.bcmj.org/articles/cholinesterase-inhibitors

Park-Wyllie, L. Y., Mamdani, M. M., Li, P., Gill, S. S., Laupacis, A., & Juurlink, D. N. (2009). Cholinesterase inhibitors and hospitalization for bradycardia: A population-based study. PLoS Med (6), 9. Retrieved from http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000157 
 
Smith, B., Chur-Hansen, A., Neale, A., & Symon, J. (2008). Quality of life and cholinesterase inhibitors: A qualitative study of patients with Alzheimer's Disease and their carers. Australasian Psychiatry, (16), 6. doi:10.1080/10398560802375990

 

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