By Dana Casciotti, PhD

May 2011

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.The FDA rejected the manufacturer’s application to expand approval to include moderate or mild Alzheimer’s.[i]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.“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.

Namenda works by decreasing abnormal activity in the brain and can therefore help people with Alzheimer’s think more clearly and accomplish daily activities more easily.[ii]However, responses to drugs differ for people at different stages of Alzheimer’s disease, so the same drug might not work for all patients.

The severity of Alzheimer’s disease 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 Alzheimer’s disease.

There is currently no cure for Alzheimer’s disease 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,[iii] 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.[iv]

In 2006, Namenda was prescribed to 19% of patients in the U.S. who had mild Alzheimer’s despite the lack of proof that it works.[v]Is this a reasonable strategy?

A study by Lon Schneider from the University of Southern California Keck School of Medicine and his colleagues published this year in the Archives of Neurology examined available evidence on the effectiveness of 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 memantine 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 memantine and placebo groups.

The study concluded that memantine was not effective in patients with mild AD. 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 memantine was very small.[vi]Looking at the trials separately, only one of the three trials found a statistically significant difference between memantine 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).

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 actually improve symptoms.Since the drug is costly and has a number of potential side-effects, patients with early Alzheimer’s disease are probably better off without Namenda.