Document Detail

Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial.
MedLine Citation:
PMID:  23290598     Owner:  NLM     Status:  MEDLINE    
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.
Adam L Boxer; David S Knopman; Daniel I Kaufer; Murray Grossman; Chiadi Onyike; Neill Graf-Radford; Mario Mendez; Diana Kerwin; Alan Lerner; Chuang-Kuo Wu; Mary Koestler; Jill Shapira; Kathryn Sullivan; Kristen Klepac; Kristine Lipowski; Jerin Ullah; Scott Fields; Joel H Kramer; Jennifer Merrilees; John Neuhaus; M Marsel Mesulam; Bruce L Miller
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  The Lancet. Neurology     Volume:  12     ISSN:  1474-4465     ISO Abbreviation:  Lancet Neurol     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-03-17     Revised Date:  2014-08-15    
Medline Journal Info:
Nlm Unique ID:  101139309     Medline TA:  Lancet Neurol     Country:  England    
Other Details:
Languages:  eng     Pagination:  149-56     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Ltd. All rights reserved.
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MeSH Terms
Chi-Square Distribution
Double-Blind Method
Excitatory Amino Acid Antagonists / therapeutic use*
Follow-Up Studies
Frontotemporal Lobar Degeneration / drug therapy*
Memantine / therapeutic use*
Middle Aged
Neuropsychological Tests
Psychiatric Status Rating Scales
Retrospective Studies
Treatment Outcome
Grant Support
P01 AG019724/AG/NIA NIH HHS; P01AG019724/AG/NIA NIH HHS; P30 AG013854/AG/NIA NIH HHS; P50 AG005146/AG/NIA NIH HHS; P50 AG1657303/AG/NIA NIH HHS; P50AG023501/AG/NIA NIH HHS; R01 AG031278/AG/NIA NIH HHS; R01 AG038791/AG/NIA NIH HHS; R01 DC008552/DC/NIDCD NIH HHS; R01AG031278/AG/NIA NIH HHS; R01AG038791/AG/NIA NIH HHS
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; W8O17SJF3T/Memantine
Comment In:
Lancet Neurol. 2013 Feb;12(2):121-3   [PMID:  23305744 ]

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