Weight Loss Associated With Cholinesterase Inhibitors in the Elderly

[[{"type":"media","view_mode":"media_crop","fid":"41351","attributes":{"alt":"© JPC-PROD/SHUTTERSTOCK.COM","class":"media-image media-image-right","id":"media_crop_3656432484128","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4353","media_crop_rotate":"0","media_crop_scale_h":"167","media_crop_scale_w":"150","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"© JPC-PROD/SHUTTERSTOCK.COM","typeof":"foaf:Image"}}]]Is cholinesterase inhibitor therapy associated with clinically significant weight loss? Cholinesterase inhibitors are commonly prescribed for dementia because they are one of the few available treatments, even though they have only modest effects on cognition and function in most patients. We already know cholinesterase inhibitors often cause gastrointestinal adverse effects (nausea, vomiting, diarrhea, and anorexia) in many patients when they are first started; however, the data on weight loss from randomized controlled trials are very limited and inconclusive.

Weight loss is an important issue in the elderly population because it has been associated with increased morbidity, functional decline, and poorer quality of life. Although weight loss is noted as an adverse effect in the existing randomized trials, the selected patient populations in these trials may not reflect drug effects in real-world settings. To understand whether cholinesterase inhibitors lead to weight loss in older adults with dementia, we studied a very large sample of patients in a real-world setting who had newly started these medications.¹

Included in the trial were 3377 patients with dementia in the VA Healthcare system: 1188 patients who had started cholinesterase inhibitors were matched with 2189 similar patients who had started other new long-term medications. The primary outcome was time to a 10-lb weight loss over a 12-month period, as this represents a degree of loss that would be clinically meaningful-not only noticeable to a clinician but that would perhaps prompt further action in considering the causes of the weight loss and medical work-up.

We used propensity score matching to control for the likelihood of receiving a cholinesterase inhibitor based on baseline characteristics, and to ensure that the groups were similar. It took into account demographic factors, baseline medical conditions and medication, baseline weight, and intensity of medical care during the past year and ensured that the 2 groups were matched on these factors.

The mean age in the study population was 78 years, 98% were male, and mean weight at baseline was 175 ± 35 lb. Of patients who started cholinesterase inhibitors, 58% were prescribed donepezil, 41% rivastigmine, and 1% galantamine. Overall, 78% of patients who started a cholinesterase inhibitor were still taking the drug 12 months later.

We found that the initiation of cholinesterase inhibitor therapy was associated with a 24% greater risk of weight loss. Overall, 29% of patients who started cholinesterase inhibitors experienced a weight loss of 10 lb or more in the first year, compared with 23% of the control group. This corresponds to a number needed to harm of 21 over 1 year, meaning only 21 patients need to be treated with a cholinesterase inhibitor over the course of a year for one patient to experience a 10-lb weight loss.

Patients with dementia who started cholinesterase inhibitors had a substantially higher risk of clinically significant weight loss over a 12-month period compared with matched controls. We did not find a group at high risk of weight loss, such as older patients, those with more medical problems, or those who were thinner to start with, but we may have been unable to detect small differences in this study.

Given that we know cholinesterase inhibitors cause nausea and anorexia, this finding may not be that surprising. However, these medications are commonly prescribed, and this adverse effect may have large implications for individuals. Clinicians should take the risk of weight loss into account when weighing the modest benefits and possible harms associated with these medications.

Cholinesterase inhibitors are prescribed often in part because there are no good treatments for dementia, and they are seen as a treatment that may or may not help but will probably not hurt. However, there are possible harms associated with these medications: initial nausea, vomiting, diarrhea, bradycardia-and now weight loss. Clinicians and prescribers should take into account and counsel patients on the possible adverse effects of weight loss when starting a cholinesterase inhibitor, monitor for weight loss if these medications are prescribed, and consider discontinuing cholinesterase inhibitors if significant weight loss occurs.

The decision to prescribe a cholinesterase inhibitor is a complex one and should be made only after a thoughtful and informed discussion with patients and their families about the possible benefits, expected adverse effects, and other risks. In addition, as recommended by the America Geriatrics Society and American Board of Internal Medicine Foundation’s Choosing Wisely initiative, periodic re-evaluation of the perceived benefits, as well as the adverse effects, should be performed regularly for every patient who is taking a cholinesterase inhibitor.

Disclosures:

Dr Sheffrin is a Geriatrics Fellow in the division of geriatrics, department of medicine at the San Francisco VA Medical Center. She reports no conflicts of interest concerning the subject matter of this article.

References:

1. Sheffrin M, Miao Y, Boscardin WJ, Steinman MA. Weight loss associated with cholinesterase inhibitors in individuals with dementia in a national healthcare system [published online ahead of print August 3, 2015]. J Am Geriatr Soc. doi: 10.1111/jgs.13511.