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Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial


Boxer, Adam L., Appels, Bregje A., Kramer, Joel H., Merrilees, Jennifer, Neuhaus, John, Mesulam, M. Marsel, Miller, Bruce L.


The Lancet. Neurology, Volume: 12, No.: 2, Pages.: 149-156

Year of Publication



Background: Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26-week open-label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the neuropsychiatric inventory (NPI). We aimed to determine whether memantine is an effective treatment for FTD.; Methods: We did a randomised, parallel group, double-blind, placebo-controlled trial of 20 mg memantine taken orally daily for 26 weeks in patients with FTD. Participants met Neary criteria for behavioural variant FTD (bvFTD) or semantic dementia and had characteristic brain atrophy. Use of acetylcholinesterase inhibitors was prohibited. Individuals were randomly assigned to receive either memantine or matched placebo tablets (1:1) in blocks of two and four patients. All patients and study personnel were masked to treatment assignment. Primary endpoints were the change in total NPI score and clinical global impression of change (CGIC) score after 26 weeks and were analysed by intention to treat. This study is registered with, number NCT00545974.; Findings: Of 100 patients screened, 81 were randomly assigned to receive memantine (39 patients) or placebo (42 patients). Five (6%) patients discontinued, and 76 completed the 26-week treatment. Enrolment numbers were lower than planned because of many patients’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. Memantine treatment had no effect on either the NPI (mean difference 2·2, 95% CI -3·9 to 8·3, p=0·47) or CGIC (mean difference 0·0, -0·4 to 0·4, p=0·90) after 26 weeks of treatment. Memantine was generally well tolerated; however, patients in the memantine group had more frequent cognitive adverse events (six patients) than those in the placebo group (one).; Interpretation: Memantine treatment showed no benefit in patients with FTD. These data do not support memantine use in FTD.; Funding: Forest Research Institute.; Copyright © 2013 Elsevier Ltd. All rights reserved.

Bibtex Citation

@article{Boxer_2013, doi = {10.1016/s1474-4422(12)70320-4}, url = {}, year = 2013, month = {feb}, publisher = {Elsevier {BV}}, volume = {12}, number = {2}, pages = {149--156}, author = {Adam L Boxer and David S Knopman and Daniel I Kaufer and Murray Grossman and Chiadi Onyike and Neill Graf-Radford and Mario Mendez and Diana Kerwin and Alan Lerner and Chuang-Kuo Wu and Mary Koestler and Jill Shapira and Kathryn Sullivan and Kristen Klepac and Kristine Lipowski and Jerin Ullah and Scott Fields and Joel H Kramer and Jennifer Merrilees and John Neuhaus and M Marsel Mesulam and Bruce L Miller}, title = {Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial}, journal = {The Lancet Neurology} }