Memantine for the treatment of Alzheimer's disease: Tolerability and safety data from clinical trials

Martin Farlow, Stephen M. Graham, Gustavo Alva

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background: Memantine, a moderate-affinity, uncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, is the first non-cholinergic agent approved for the treatment of Alzheimer's disease (AD), and the first medication approved in the US and Europe for the treatment of moderate to severe stages of the disease. The objective of this study was to analyse safety and tolerability data from phase III memantine trials and from the open-label extensions of those trials. Method: We conducted an analysis of the pooled data for tolerability and safety from six double-blind, placebo-controlled, memantine trials with a minimum duration of 24 weeks (three trials in mild to moderate AD and three in moderate to severe AD; 20 mg/day; 2311 patients) and four open-label extensions of those trials (two in mild to moderate AD and two in moderate to severe AD; 20 mg/day, 1405 patients), for a total treatment period of up to 2 years. Results: The analysis revealed that adverse events occurring during both short- and long-term memantine treatment were minimal, and similar in type and frequency to those reported for placebo-treated patients. The most frequently reported adverse events in placebo-controlled trials included agitation (7.5% memantine vs 12.0% placebo), falls (6.8% vs 7.1%), dizziness (6.3% vs 5.7%), accidental injury (6.0% vs 7.2%), influenza-like symptoms (6.0% vs 5.8%), headache (5.2% vs 3.7%) and diarrhoea (5.0% vs 5.6%). Discontinuations due to adverse events were similar in memantine- and placebo-treated groups (8.9% vs 9.8%, respectively). Conclusion: Consistent with the favourable tolerability profile of memantine observed in clinical use, this analysis of pooled safety data indicates that both short- and long-term memantine treatment of patients with AD is safe and well tolerated, with an adverse event profile similar to that of placebo.

Original languageEnglish
Pages (from-to)577-585
Number of pages9
JournalDrug Safety
Volume31
Issue number7
DOIs
StatePublished - 2008

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Memantine
Alzheimer Disease
Clinical Trials
Safety
Placebos
Therapeutics
Labels
Dizziness
N-Methyl-D-Aspartate Receptors
Human Influenza
Headache
Diarrhea
Wounds and Injuries

Keywords

  • Alzheimer's disease, treatment
  • Memantine, adverse reactions

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Memantine for the treatment of Alzheimer's disease : Tolerability and safety data from clinical trials. / Farlow, Martin; Graham, Stephen M.; Alva, Gustavo.

In: Drug Safety, Vol. 31, No. 7, 2008, p. 577-585.

Research output: Contribution to journalArticle

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abstract = "Background: Memantine, a moderate-affinity, uncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, is the first non-cholinergic agent approved for the treatment of Alzheimer's disease (AD), and the first medication approved in the US and Europe for the treatment of moderate to severe stages of the disease. The objective of this study was to analyse safety and tolerability data from phase III memantine trials and from the open-label extensions of those trials. Method: We conducted an analysis of the pooled data for tolerability and safety from six double-blind, placebo-controlled, memantine trials with a minimum duration of 24 weeks (three trials in mild to moderate AD and three in moderate to severe AD; 20 mg/day; 2311 patients) and four open-label extensions of those trials (two in mild to moderate AD and two in moderate to severe AD; 20 mg/day, 1405 patients), for a total treatment period of up to 2 years. Results: The analysis revealed that adverse events occurring during both short- and long-term memantine treatment were minimal, and similar in type and frequency to those reported for placebo-treated patients. The most frequently reported adverse events in placebo-controlled trials included agitation (7.5{\%} memantine vs 12.0{\%} placebo), falls (6.8{\%} vs 7.1{\%}), dizziness (6.3{\%} vs 5.7{\%}), accidental injury (6.0{\%} vs 7.2{\%}), influenza-like symptoms (6.0{\%} vs 5.8{\%}), headache (5.2{\%} vs 3.7{\%}) and diarrhoea (5.0{\%} vs 5.6{\%}). Discontinuations due to adverse events were similar in memantine- and placebo-treated groups (8.9{\%} vs 9.8{\%}, respectively). Conclusion: Consistent with the favourable tolerability profile of memantine observed in clinical use, this analysis of pooled safety data indicates that both short- and long-term memantine treatment of patients with AD is safe and well tolerated, with an adverse event profile similar to that of placebo.",
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