According to a 2007 article on the severe side effects of memantine and other drugs for Alzheimer’s disease, cardiovascular events were the most frequent type of serious side effect reported. The article states that “the potential benefits of these treatments are often too limited to warrant exposing patients to the risk of such serious adverse effects.”
Thirty-six cases of cardiovascular adverse events associated with memantine use were reported to France's PharmacoVigilance Database. There were 18 cases of bradycardia (slow heart rate) and 18 cases of various other cardiovascular reactions.
The liver partially metabolizes memantine. Though no dosage adjustment is needed in patients with mild or moderate liver impairment, memantine should be administered with caution to patients with severe liver impairment.
Studies show ...
In a review of memantine, the editors of Prescrire International state: “Data on the effects of memantine in severe Alzheimer’s disease are sparse and weak.”
Authors in another medical journal, the Drug and Therapeutics Bulletin, agreed with the statements in Prescrire International, concluding their review of the drug by saying:
On published evidence, memantine produces, at best, only a small reduction in the rate of deterioration in global, functional, and cognitive scales in such patients. Whether this translates into important changes in quality of life or how long the effects last is unclear.
A meta-analysis was undertaken by the Cochrane Collaboration to determine efficacy and safety of memantine for people with Alzheimer’s disease, vascular and mixed dementia. Their published review stated:
The conclusion of the data suggest a small beneficial effect of memantine at six months in moderate to severe [Alzheimer's disease]. The beneficial effect on cognition in patients with mild to moderate vascular dementia was not detectable on global assessment at six months. Whether memantine has any effect in mild to moderate [Alzheimer’s disease] is unknown.
One highly touted study purports to show that that using memantine significantly decreases caregiver time spent helping those with Alzheimer’s disease. Although this study allegedly randomized patients to get either memantine or a placebo, before the patients ever got their drugs there were statistically significant differences between the patients who eventually got the placebo and those who eventually were given memantine. Thus, any conclusions about the positive effects of the drug are, at the least, highly suspect.
A study published in the April 2011 medical journal Archives of Neurology revealed no statistical differences in outcomes between mild Alzheimer’s disease patients treated with memantine and those given a placebo.
Drug barely meets FDA guidelines
The FDA guidelines for approval of drugs to treat Alzheimer’s disease require that studies demonstrate a statistically significant effect on two primary outcome measures: (1) cognitive function; and (2) global patient functioning or activities of daily function. The FDA medical officer reviewing the data submitted by the drug's manufacturer, Forest Laboratories, stated: “There was a small effect size [difference] between memantine treated and placebo treated groups on cognitive improvement.”
He continued to comment on the measures of global functioning: “Only a small minority of patients treated with memantine showed even a minimal or moderate improvement, with no patients showing a marked improvement, and the most common response being no change.”
Furthermore, an FDA statistician's analysis of a subgroup of patients showed memantine failed to demonstrate a significant effect on patient global function for severe dementia of the Alzheimer’s type.
Although memantine shows a modest effect on improvement compared with placebo for moderately severe Alzheimer’s disease, the effectiveness of memantine has not been compared with any of the acetylcholinesterase inhibitors, none of which has persuasive evidence of efficacy.
The effect of memantine on the progression of the disease is summed up in the drug’s professional product labeling, which states: “At this time, there is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease.”
Regulatory action surrounding memantine
2005: The FDA revised the drug product label to include hepatic and renal impairment.