An Open-Label Trial of Memantine for Cognitive Impairment in Patients With Post-Traumatic Stress Disorder
Condition: PTSD
MeSH terms: Cognitive Dysfunction; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 4

Summary: 
      Twenty six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an
      open label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and
      Letter-Number Sequencing subtests of the Wechsler Memory Scale III (Third edition) and the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS measures
      attention, language, visuospatial skills, and immediate and delayed memories. The Clinician
      Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale
      (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan
      Disability Scale (SDS) were used to assess improvement in PTSD symptoms, as secondary outcome
      measures.
    

Detailed description: 
      Participants were recruited from the Omaha Veterans Affairs Medical Center following local
      IRB approval. We obtained written consent from all the subjects who were recruited in the
      study. Veterans between the ages of 19 and 65 years with chronic PTSD (diagnosis for >6
      months) attributable to military combat exposure were included in the study. Patients were
      required to be clinically stable on their psychotropic medication regimen for at least three
      months prior to study entry. In addition to meeting DSM-IV criteria for PTSD and endorsing
      subjective complaints of memory difficulties, patients had to score least one standard
      deviation below the mean performance of a standardized, age- and sex-matched population on
      the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler
      Memory Scale III (Third edition) for study entry. Patients with a history of dementia,
      schizophrenia, bipolar disorder, traumatic brain injury, and seizure were excluded. Patients
      with any history of alcohol or illicit drug abuse or dependence within the past one month
      were excluded. Patients requiring concomitant treatment with drugs with potential effects on
      the glutamergic system, such as amantadine,dextromethorphan, or carbonic anhydrase
      inhibitors, were excluded.

      Subjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day
      in divided doses to a dose of 20 mg/day. Memory was assessed using the Repeatable Battery for
      the Assessment of Neuropsychological Status (RBANS) [Randolph, 1998] using both forms A and B
      at baseline, end of week 8, and end of week 16. The RBANS is composed of 10 subtests that
      yield a total score and five index scores: immediate memory, visuospatial/constructional,
      language, attention, and delayed memory. Each index score has a normal mean of 100 and
      standard deviation of 15 based on the performance of a standardization sample matched to the
      U.S. Census on sex, ethnicity, and level of education. Alternative forms of the RBANS (Forms
      A and B) were used to avoid bias due to practice effects. We administered Clinician
      Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale
      (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan
      Disability Scale (SDS) to assess the secondary measures. Changes in the scores over time with
      repeated measures were estimated with mixed-effects models. The primary outcome measures of
      interest were index and percentile scores in RBANS total and subscale scores. The repeated
      measures model included visit (as a categorical variable) as a fixed effect. An unstructured
      covariance matrix was used to fit the within patient repeated measures effect. Tukey's method
      was used to compare pair-wise means.

      Secondary outcome measures, CAPS, HAM-A, HAM-D, Q-LES-Q, and SDS, were analyzed similarly to
      the RBANS with repeated measures models. P-values less than 0.05 are considered to be
      statistically significant. SAS software version 9.1 (SAS Institute, Cary, NC) was used for
      the analysis
    

Intervention name(s): Memantine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day in divided doses to a dose of 20 mg/day; Matched placebo
Other intervention name(s): Namenda
Intervention MeSH terms: Memantine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment