Critical appraisal and role of memantine extended-release in the management of Alzheimer’s disease

Abstract

Correspondence: indrapal Singh Department of Neurology and Psychiatry, Division of Geriatric Psychiatry, Saint Louis University School of Medicine, 1438 South Grand Blvd, St Louis, MO 63108, USA Tel +1 314 977 4829 Fax +1 314 977 4878 email isingh2@slu.edu Abstract: Alzheimer’s disease (AD) is a progressive, degenerative brain disease. Currently available US FDA-approved pharmacological management options for AD are cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N-methyl-D-aspartate receptor antagonist (memantine). These treatment options may provide symptomatic benefits. Medication adherence is one of the many problems faced by the caregivers of patients with dementia. The currently available FDA-approved memantine immediate-release (IR) has been found safe and efficacious at a dose of 10 mg twice daily (20 mg/day) both as monotherapy and in combination with cholinesterase inhibitors in moderate to severe dementia. Memantine extended-release (ER) 28 mg, a new once-daily form at a higher dose, has also been found to be safe and well tolerated in 2 studies: one in 24 healthy volunteers which showed relatively minor fluctuation in plasma levels of memantine during the steady-state dosing interval and second, a multinational multi-center study, comparing memantine ER 28 mg and placebo in patients with moderate to severe AD stable on concurrent cholinesterase inhibitor (ChEI). In this study, memantine ER was found to be an efficacious drug with a good safety and tolerability profile. Both memantine IR 20 mg and memantine ER 28 mg are now FDA-approved for the treatment of moderate to severe AD, either alone, or in combination with a ChEI. Both are efficacious, safe, and well tolerated. Medication adherence with the ER preparation should improve because of once-daily dosing. There is a possibility of superior efficacy of the higher dose memantine ER (28 mg) over the currently approved dosage of memantine IR (20 mg). However, further randomized, controlled, double-blind comparator studies of memantine ER 28 mg vs memantine IR 20 mg and/or 30 mg in single and/or divided doses are required to assess the possible benefits of memantine ER over memantine IR.