Randomized, placebo-controlled, crossover trial of memantine for cognitive changes with corticosteroid therapy

Biol Psychiatry. 2008 Oct 15;64(8):727-9. doi: 10.1016/j.biopsych.2008.05.010. Epub 2008 Jun 25.


Background: In animal models, corticosteroids are associated with changes in hippocampal structure and functioning that are prevented by glutamate release inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists. Cushing's disease and prescription corticosteroid administration are also associated with memory impairment and hippocampal atrophy. Use of NMDA receptor antagonists to attenuate corticosteroid effects in humans has not been investigated. We examine the NMDA receptor antagonist memantine in patients receiving corticosteroids.

Methods: Twenty outpatients receiving long-term oral corticosteroid therapy were randomized to 8 weeks of memantine (maximum dose 20 mg/day) and 8 weeks of placebo in a double-blind fashion, with a 4-week washout period between courses. Declarative memory was assessed with the Hopkins Verbal Learning Test (HVLT) and mood with the Hamilton Rating Scale for Depression and Young Mania Rating Scale. Changes in outcome measures were compared during memantine and placebo exposure.

Results: Seventeen participants completed both treatment phases and were used in the analysis. Significant improvement (p < .05) in total and delayed recall on the HVLT was observed with memantine as compared with placebo. No significant changes in mood were observed.

Conclusions: Memantine therapy was associated with improvement in declarative memory but not mood in patients receiving prescription corticosteroids.

Trial registration: ClinicalTrials.gov NCT00280774.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Cognition Disorders / chemically induced
  • Cognition Disorders / prevention & control*
  • Cross-Over Studies
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Female
  • Hippocampus / drug effects
  • Humans
  • Male
  • Memantine / therapeutic use*
  • Middle Aged
  • Nootropic Agents / therapeutic use*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Statistics, Nonparametric
  • Treatment Outcome
  • Verbal Learning / drug effects*
  • Young Adult


  • Adrenal Cortex Hormones
  • Excitatory Amino Acid Antagonists
  • Nootropic Agents
  • Receptors, N-Methyl-D-Aspartate
  • Memantine

Associated data

  • ClinicalTrials.gov/NCT00280774