Randomized, placebo-controlled, crossover trial of memantine for cognitive changes with corticosteroid therapy.
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.
Brown
E Sherwood
ES
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: Sherwood.Brown@UTSouthwestern.edu.
Vazquez
Miguel
M
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Nakamura
Alyson
A
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas.
D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014706:Verbal Learning / Q000187:drug effects*; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine