Namenda only works for severe Alzheimer’s disease and dementia

By Dana Casciotti, PhD and Stephanie Fox-Rawlings, PhD

Updated 2016

Namenda (also called Memantine) was approved by the FDA in 2003 for use in people with “moderate to severe” Alzheimer’s disease or other types of dementia. The FDA rejected the manufacturer’s application to expand approval to include mild Alzheimer’s or dementia.1 However, the drug is often prescribed “off-label” for patients with mild Alzheimer’s or dementia even though there is little evidence of its benefit at this stage of disease 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. It is currently impossible to be sure if the type of dementia is caused by Alzheimer’s disease until there is an autopsy. Doctors can make a probable diagnosis through additional lab tests. These tests cannot diagnose Alzheimer’s disease, but rule out other causes for dementia symptoms, some of which should be treated differently. These tests are expensive and can be very time consuming.  For that reason, studies of “Alzheimer’s disease” are usually studies of people with multiple types of dementia, so we use the terms interchangeably in this article.

The severity of dementia 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.

Depending on which drug they are taking, patients are usually prescribed between 3mg-20mg each day. The cost of a generic version of Namenda (20mg/day) is typically a little more than of the generic version of Aricept (10mg/day), and seems to be less effective for most patients. The generic versions of Razadyne and Exelon are usually more expensive, but this varies depending on insurance coverage and where the drugs are purchased. Aricept, Razadyne, and Exelon work in the same way in the brain, while Namenda works through a different system. That is why doctors sometimes hope that adding Namenda to Aricept or the other drugs might have an added benefit for patients with moderate or severe dementia.

There is no cure for most types of dementia and treatments are not very effective. Current drugs merely delay decline and help reduce symptoms.  Patients with mild Alzheimer’s disease won’t benefit from Namenda but will cost them money and could cause side effects. Some side effects of Namenda are 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.2

A study by Lon Schneider and his colleagues from the University of Southern California Keck School of Medicine examined available evidence on the effectiveness of Namenda in patients with mild Alzheimer’s disease. 3  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.3 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.3 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.3 Looking at the trials separately, only one of the three trials found any statistically significant improvement for patients taking Namenda compared to patients taking placebo. Even that improvement was for only one measure – a subjective measure of the doctor or caregiver’s impressions of the patients’ behavior. When the data were combined, there was a statistically significant effect on cognitive functioning and impression of change. However, these differences were small—about half the impact of drugs like Aricept, Exelon, or Razadyne, which are commonly prescribed to treat Alzheimer’s symptoms.

A 2014 study found that male military veterans with mild or 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. Several other studies have also suggested that vitamin E can provide a moderate benefit for Alzheimer’s patients.4  However, high levels of vitamin E may be dangerous, sometimes increasing the chances of heart failure and death.5 For more information on vitamin E, please visit here.

More recent meta-analyses have evaluated Namenda for dementia ranging from mild to severe, based on  randomized controlled trials.  These have found a significant benefit of Namenda compared to placebo for patients with dementia ranging from moderate to severe for cognitive function, behavioral disturbances, and ability to function in activities related to daily life dementia, but not for patients with milder dementia.6 7 8

None of the current treatments for dementia will radically improve patients’ memory or thinking, nor will they stop the progression of the disease. However, Namenda may help moderate or severe dementia, while Aricept, Razadyne, or Exelon may help patients with dementia ranging from mild to severe.





  1. Forest Receives Non-Approvable Letter for Expanded Namenda Indication. Drug Industry Daily, Vol. 4 No. 145. July 26, 2005.  
  2. National Library of Medicine. Medline Plus. Memantine.  
  3. Schneider LS, Dagerman KS, Higgins JP, McShane R (2011). Lack of Evidence for the Efficacy of Memantine in Mild Alzheimer Disease. Arch Neurol. 68(8):991-998.  
  4. La Fata G, Weber P, & Mohajeri MH (2014). Effects of Vitamin E on Cognitive Performance during Ageing and in Alzheimer’s Disease. Nutrients. 6:5453-547.  
  5. American Psychiatric Association (2010). Practice guideline for the treatment of patients with Alzheimer’s Disease and other dementias. Second edition.  
  6. Matsunaga S, Kishi T, & Iwata N (2015). Memantine monotherapy for Alzheimer’s disease: A systematic review and meta-analysis. PLoS ONE. 10(4):e0123289.  
  7. Di Santo SG, Princelli F, Adorni F, Caltagirone C, & Musicco M (2013). A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer’s disease. Journal of Alzheimer’s Disease.35:349-361.  
  8. Rive B, Gauthier S, Costello S, Marre C, & Francois C (2013). Synthesis and comparison of the meta-analyses evaluating the efficacy of memantine in moderate to severe stages of Alzheimer’s disease. CNS Drugs. 27:573-582.