By Dana Casciotti, PhD
Memantine, known by the brand name Namenda, was approved by the FDA in 2003 for use in people with “moderately severe to severe” Alzheimer’s disease or dementia.The FDA rejected the manufacturer’s application to expand approval to include moderate or mild Alzheimer’s or dementia.1 However, the drug is often prescribed “off-label” for patients with mild Alzheimer’s and mild cognitive impairment even though there is no evidence of its benefit and other drugs, such as Aricept and Razadyne, are more effective. “Off label” means that the use is not on the FDA-approved label for the drug, because of lack of proof that it is safe and effective for that use.
Although “Alzheimer’s disease” is the more common diagnosis, Alzheimer’s disease is just one type of dementia and it is usually impossible to tell them apart until there is an autopsy. Studies of “Alzheimer’s disease” are usually studies of people with dementia, so we use the terms interchangeably in this article. Namenda works by decreasing abnormal activity in the brain and can therefore help people with Alzheimer’s or other dementias think more clearly and accomplish daily activities more easily.2 However, responses to drugs differ for people at different stages of dementia, so the same drug might not work for all patients.
The severity of these diseases is usually diagnosed using a test called the Mini-Mental State Examination (MMSE). A score of around 20-23 usually indicates mild disease; 10-19 indicates moderate to moderately severe disease; and less than 10 is considered severe disease.
There is currently no cure for most dementia and treatments have limited effectiveness. For that reason, doctors, patients, and family members are willing to try almost anything. But Namenda is an expensive drug, costing an estimated $1,600 a year,3 and can cause debilitating side effects such as extreme fatigue, dizziness, confusion, headache, sleepiness, constipation, vomiting, pain (especially in the back), and coughing. More serious side effects are rare but include shortness of breath and hallucination.4
In 2006, Namenda was prescribed to 19% of patients in the U.S. who had mild Alzheimer’s or dementia despite the lack of proof that it works.5 Is this a reasonable strategy?
A study by Lon Schneider from the University of Southern California Keck School of Medicine and his colleagues published in 2011 in the Archives of Neurology examined available evidence on the effectiveness of Namenda (memantine) in patients with mild Alzheimer’s disease. The researchers conducted a meta-analysis, meaning they pooled and analyzed data available from several different clinical trials, in order to evaluate a larger number of people. They analyzed data from three clinical trials that included 431 patients with mild Alzheimer’s disease and 697 patients with moderate Alzheimer’s.
All three clinical trials randomly assigned patients to either receive Namenda or a placebo, and neither patients nor investigators were aware of who was receiving the drug and who was not. This is called a “double-blind” study and it prevents bias based on expectations that a drug will improve the outcome being measured. In this case, investigators measured patient’s cognitive functioning, behavior, and ability to perform activities of daily living. They also measured “impression of change” in the patient according to the patient’s clinician and caregiver. Four different scales were used to measure these outcomes and then scores were compared between the Namenda and placebo groups.
The study concluded that Namenda was not effective in patients with mild dementia.This was true when they looked at each trial separately and also when they pooled data from the three studies and analyzed that.
Among patients with moderate Alzheimer’s disease, the effect of Namenda was very small.6 Looking at the trials separately, only one of the three trials found a statistically significant difference between Namenda and placebo. But that effect was seen on only one of the four outcomes measured (the impression of change according to clinician and caregiver). When the data were combined there was a statistically significant effect on two of the four outcomes measured: cognitive functioning and impression of change. However, the effects were small—about half the effect sizes seen in clinical trials of cholinesterase inhibitors (drugs like Aricept or Razadyne that are commonly prescribed to treat Alzheimer’s symptoms).
A 2014 study found that male military veterans with mild to moderate dementia did not benefit from Namenda, whether taken alone or together with vitamin E.7 However, vitamin E taken alone did slow the progression of mild to moderate Alzheimer’s. More research is needed to determine if vitamin E has the same effects on women with mild to moderate dementia, but these findings suggest that vitamin E is a more effective, lower-cost treatment than Namenda. For more information on vitamin E, please visit here.
Depending on which drug they are taking, patients are usually prescribed between 10mg-20mg each day. The cost of Namenda (20mg/day) is similar to the cost of the generic version of Aricept (10mg/day), but it seems to be less effective. The generic version of Razadyne (12mg/day) is the cheapest of the three drugs.
This study suggests that frequent off-label prescriptions of Namenda to mild Alzheimer’s patients do not improve symptoms. Since the drug is costly and has a number of potential side-effects, patients with early Alzheimer’s disease or dementia are likely to be better off without Namenda.
- Forest Receives Non-Approvable Letter for Expanded Namenda Indication.Drug Industry Daily, Vol. 4 No. 145. July 26, 2005. ▲
- National Library of Medicine. Medline Plus, Drugs & Supplements: href=”http://www.nlm.nih.gov/medlineplus/druginfo/meds/a604006.html”>http://www.nlm.nih.gov/medlineplus/druginfo/meds/a604006.html.Accessed May 16, 2011. ▲
- American Academy of Family Physicians, Memantine (Namenda) for Moderate to Severe Alzheimer’s Disease href=”http://www.aafp.org/afp/2004/0315/p1491.html”>http://www.aafp.org/afp/2004/0315/p1491.html ▲
- National Library of Medicine. Medline Plus, Drugs & href=”http://www.nlm.nih.gov/medlineplus/druginfo/meds/a604006.html”>http://www.nlm.nih.gov/medlineplus/druginfo/meds/a604006.html. Accessed May 16, 2011. ▲
- McManus T. Stakeholder insight: Alzheimer’s disease-prescribing trends indicate that neurologists are not adhering to guidelines. Datamonitor Web site. href=”http://www.marketresearch.com/vendors/viewVendor.asp?VendorID=72″>http://www.marketresearch.com/vendors/viewVendor.asp?VendorID=72.December 2006. ▲
- Schneider LS, Dagerman KS, Higgins JP, McShane R (2011). Lack of Evidence for the Efficacy of Memantine in Mild Alzheimer Disease. Arch Neurol. Apr 11. (Epub ahead of print) href=”http://www.archneurol.com/”>www.archneurol.com ▲
- Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease. JAMA; 2014; 311(1):33-44. doi: 10.1001/jama.2013.282834 ▲