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

• Published in: Lancet neurology Vol. 12; no. 2; pp. 149 - 156
• Main Authors: Boxer, Adam L, Knopman, David S, Kaufer, Daniel I, Grossman, Murray, Onyike, Chiadi, Graf-Radford, Neill, Mendez, Mario, Kerwin, Diana, Lerner, Alan, Wu, Chuang-Kuo, Koestler, Mary, Shapira, Jill, Sullivan, Kathryn, Klepac, Kristen, Lipowski, Kristine, Ullah, Jerin, Fields, Scott, Kramer, Joel H, Merrilees, Jennifer, Neuhaus, John, Mesulam, M Marsel, Miller, Bruce L
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2013; Elsevier Limited
• Subjects: Acetylcholinesterase; Aged; Alzheimer's disease; Antipsychotics; Aphasia; Atrophy; Behavior; Blister packs; Brain; Caregivers; Chi-Square Distribution; Cholinesterase; Clinical trials; Cognitive ability; Data processing; Dementia; Disease; Double-Blind Method; Drug dosages; Excitatory Amino Acid Antagonists - therapeutic use; FDA approval; Female; Follow-Up Studies; Forests; Frontotemporal dementia; Frontotemporal Lobar Degeneration - drug therapy; Humans; Inventories; Male; memantine; Memantine - therapeutic use; Middle Aged; Motivation; Neurology; Neuropsychological Tests; Neuropsychology; Parkinson's disease; Patients; Personnel; Psychiatric Status Rating Scales; Psychotropic drugs; Retrospective Studies; semantic dementia; Semantics; Tablets; Treatment Outcome; United States > US; California
• ISSN: 1474-4422; 1474-4465; 1474-4465
• DOI: 10.1016/S1474-4422(12)70320-4

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. 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. 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). Memantine treatment showed no benefit in patients with FTD. These data do not support memantine use in FTD. Forest Research Institute.