The article you requested is

Memantine for Fragile X–Associated Tremor/Ataxia Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

J Clin Psychiatry 2014;75(3):264-271

Objective: Memantine, an uncompetitive N-methyl-d-aspartate receptor antagonist, is currently approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer’s disease. Anecdotal reports have suggested that memantine may improve neurologic and cognitive symptoms of individuals with the neurodegenerative disease fragile X–associated tremor/ataxia syndrome (FXTAS); however, its efficacy and safety in this population have not been assessed in a controlled trial.

Method: Individuals with FXTAS aged 34–80 years were enrolled in a randomized, double-blind, placebo-controlled, 1-year trial between September 2007 and August 2012. Inclusion required definite, probable, or possible FXTAS in clinical stages 1–5 according to previously published criteria. Primary outcome measures were the Behavioral Dyscontrol Scale (BDS) score and CATSYS intention tremor severity.

Results: Ninety-four participants were randomized from 205 screened; of those, 43 and 45 started treatment with memantine (titrated to 10 mg twice daily) and placebo, respectively. Thirty-four participants receiving memantine and 36 receiving placebo completed the 1-year endpoint assessment (n = 70). Intention-to-treat analysis showed no improvement with respect to intention tremor severity (mean [SD] values with memantine vs placebo: 1.05 [0.73] vs 1.89 [2.19], P = .047) or BDS score (16.12 [5.43] vs 15.72 [3.93], P = .727) at follow-up. Post hoc analyses of participants with early FXTAS (stage ≤ 3), those with late FXTAS (stage > 3), and those in different age groups (≤ 65 years and > 65 years) also indicated no significant improvement. More frequent mild adverse events were observed in the placebo group, while more frequent moderate adverse events occurred in the memantine group (P = .007).

Conclusion: This randomized, double-blind, placebo-controlled trial of memantine for individuals with FXTAS showed no benefit compared to placebo with respect to the selected outcome measures.

Trial Registration: identifier: NCT00584948

J Clin Psychiatry

Submitted: April 20, 2013; accepted July 12, 2013.

Online ahead of print: December 10, 2013 (doi:10.4088/JCP.13m08546).

Corresponding author: Andreea L. Seritan, MD, 2230 Stockton Blvd, Sacramento, CA 95817 (