TY - JOUR
T1 - Memantine in patients with frontotemporal lobar degeneration
T2 - A multicentre, randomised, double-blind, placebo-controlled trial
AU - Boxer, Adam L.
AU - Knopman, David S.
AU - Kaufer, Daniel I.
AU - Grossman, Murray
AU - Onyike, Chiadi
AU - Grant, Ian Michael
AU - Mendez, Mario
AU - Kerwin, Diana
AU - Lerner, Alan
AU - Wu, Chuang Kuo
AU - Koestler, Mary
AU - Shapira, Jill
AU - Sullivan, Kathryn
AU - Klepac, Kristen
AU - Lipowski, Kristine
AU - Ullah, Jerin
AU - Fields, Scott
AU - Kramer, Joel H.
AU - Merrilees, Jennifer
AU - Neuhaus, John
AU - Mesulam, M. Marsel
AU - Miller, Bruce L.
PY - 2013/2
Y1 - 2013/2
N2 - 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 Clinicaltrials.gov, 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.
AB - 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 Clinicaltrials.gov, 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.
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U2 - 10.1016/S1474-4422(12)70320-4
DO - 10.1016/S1474-4422(12)70320-4
M3 - Article
C2 - 23290598
AN - SCOPUS:84872382183
SN - 1474-4422
VL - 12
SP - 149
EP - 156
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 2
ER -