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. Cushingʹs 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.