UCSF researchers recommend clinicians account for risk when prescribing to older adults.
Medications commonly used to treat dementia could result in harmful weight loss, according to UC San Francisco researchers, and clinicians need to account for this risk when prescribing these drugs to older adults, they said.
Their study appears online and in the August issue of the Journal of the American Geriatrics Society.
“This is very relevant to patient care because unintentional weight loss in older adults is associated with many adverse outcomes, including increased rates of institutionalization and mortality, a decline in functional status, and poorer quality of life,” said lead author Meera Sheffrin, MD, geriatrics fellow in the UCSF School of Medicine at the UCSF-affiliated San Francisco VA Medical Center. “Our study provides evidence in a large, real-world population that cholinesterase inhibitors may contribute to clinically significant weight loss in a substantial proportion of older adults with dementia.”
Alzheimer’s disease and other dementias are prevalent, affecting one in six people over age 80. The main drug treatments, a class of medications called cholinesterase inhibitors (i.e., donepezil, galantamine, rivastigmine), are marginally beneficial for most patients and may have serious side effects such as gastrointestinal symptoms.
Weight loss also is a significant problem in dementia patients and linked to increased mortality. Data from randomized controlled trials suggests this weight loss may be an under-recognized side effect of cholinesterase inhibitors, but evidence is limited and conflicting.
In this study, Sheffrin and her colleagues used national VA data from 2007-2010 to evaluate patients age 65 or older diagnosed with dementia who received a new prescription for a cholinesterase inhibitor or other new chronic medication. The primary outcome was timed to a 10-pound weight loss over a 12-month period, as this represents a degree of loss that would be noticed by a clinician and perhaps prompt further action in considering the causes and potential treatments.
A total of 1,188 patients started on cholinesterase inhibitors were matched to 2,189 patients started on other medications. At 12 months, 78 percent were still on the inhibitors, compared to 66 percent for other medications. About 29.3 percent of patients on the inhibitors experienced significant weight loss, compared to 22.8 percent of non-users.
These results demonstrated that patients started on the medications had a higher risk of clinically significant weight loss over a 12-month period compared to matched controls, Sheffrin said. Specifically, one out of every 21 patients treated experienced at least a 10-pound weight loss.
Further research is needed to validate these findings and address study limitations, including if there is a specific subgroup in which starting cholinesterase inhibitors had a higher risk of weight loss, as this study may have been underpowered to find those differences. The sample also included mainly older male veterans, so the generalizability of the findings to women is uncertain, the researchers said.
“Clinicians should take into account the risk of weight loss when weighing the risks and benefits of prescribing cholinesterase inhibitors in patients with dementia,” the authors write. “In addition, clinicians should monitor for weight loss if these medications are prescribed and consider discontinuing cholinesterase inhibitors if significant weight loss occurs.”
About this neuropharmacology research
Other UCSF contributors to the Journal of the American Geriatrics Society study were senior author Mike Steinman, MD, associate professor, and Yinghui Miao, MD, MPH, statistician, of geriatrics; and W. John Boscardin, PhD, professor of epidemiology and biostatistics.
Funding: Funding was provided by the National Institute on Aging and the American Federation on Aging Research.
Source: Scott Maier – UCSF Image Credit: The image is credited to the NIH and is in the public domain Original Research:Abstract for “Weight Loss Associated with Cholinesterase Inhibitors in Individuals with Dementia in a National Healthcare System” by Meera Sheffrin, Yinghui Miao, W. John Boscardin and Michael A. Steinman in Journal of the American Geriatrics Society. Published online August 3 2015 doi:10.1111/jgs.13511
Weight Loss Associated with Cholinesterase Inhibitors in Individuals with Dementia in a National Healthcare System
Objectives To determine whether initiation of cholinesterase inhibitors is associated with significant weight loss in a real-word clinical setting.
Design Retrospective cohort study from 2007 to 2010 comparing weight loss in individuals with dementia newly prescribed cholinesterase inhibitors and those newly prescribed other chronic medications.
Setting National Veterans Affairs data.
Participants Individuals aged 65 and older with a diagnosis of dementia who received a new prescription for a cholinesterase inhibitor or other new chronic medication.
Measurements The primary outcome was time to 10-pound weight loss over 12 months. Propensity score matching was used to control for the likelihood of receiving a cholinesterase inhibitor based on baseline characteristics. Data were analyzed in a priori defined subgroups according to age, comorbid burden, and initial weight.
Results Of 6,504 individuals that met study criteria, 1,188 started on cholinesterase inhibitors were matched to 2,189 started on other medications. The propensity-matched cohorts were well balanced on baseline covariates. Participants initiated on cholinesterase inhibitors had a higher risk of weight loss than matched controls at 12 months (hazard ratio = 1.23, 95% confidence interval (CI) = 1.07–1.41). At 12 months, 29.3% of participants taking cholinesterase inhibitors had experienced weight loss, compared with 22.8% of nonusers, corresponding to a number needed to harm of 21.2 (95% CI = 12.5–71.4) over 1 year. There were no significant differences in the risk of weight loss within subgroups.
Conclusion These results are consistent with the available data from randomized controlled trials. Clinicians should consider the risk of weight loss when prescribing cholinesterase inhibitors.
“Weight Loss Associated with Cholinesterase Inhibitors in Individuals with Dementia in a National Healthcare System” by Meera Sheffrin, Yinghui Miao, W. John Boscardin and Michael A. Steinman in Journal of the American Geriatrics Society. Published online August 3 2015 doi:10.1111/jgs.13511