title: Memantine for AIDS dementia complex: open-label report of ACTG 301.
abstract: OBJECTIVE
  To evaluate the long-term safety and efficacy of memantine use as treatment of HIV-associated cognitive impairment.
  
  
  BACKGROUND
  The results of a 20-week, randomized, double-blind, placebo-controlled trial of memantine in HIV-infected participants with cognitive impairment (ACTG 301) were previously reported. We report the results of the up-to-60-week open-label phase following the double-blind phase.
  
  
  METHODS
  Participants received open-label memantine and were escalated to a 40 mg/day dose or their maximum tolerated dose in the double- blind phase. Adverse experiences were used to evaluate safety, and changes in the mean of eight neuropsychological test scores (NPZ-8) were used to evaluate efficacy.
  
  
  RESULTS
  Ninety-nine participants entered the initial 12-week open-label phase and 45 in the additional 48-week extension. Twenty-seven participants reported severe adverse experiences. During the initial 12-week open-label phase, participants randomized to memantine in the double-blind phase had a statistically significant higher improvement in NPZ-8 compared to those randomized to placebo in the double-blind phase. No statistically significant NPZ-8 changes were detected during the 48-week extension.
  
  
  CONCLUSIONS
  Long-term use of memantine appears safe and tolerable. Future randomized studies with longer follow-up are necessary to establish efficacy of memantine for the treatment of HIV-associated cognitive impairment.
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts, USA. yu.zhao@fda.hhs.gov
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Navia
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Joseph
authors.initials: J
authors.lastname: Berger
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kolson
authors.forename: David
authors.initials: D
authors.lastname: Simpson
authors.forename: Eric N
authors.initials: EN
authors.lastname: Miller
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lipton
authors.forename: Scott R
authors.initials: SR
authors.lastname: Evans
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000523:psychology; D000328:Adult; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D015497:HIV-1; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D018709:Statistics, Nonparametric
chemical_list: D015259:Dopamine Agents; D008559:Memantine
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