Conditions: Memory Impairment
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 54
Healthy volunteers: no

Brief summary:
Medically stable outpatients receiving chronic oral corticosteroid therapy were enrolled in a 48-week randomized, double-blind, placebo-controlled, parallel-group, trial of lamotrigine.

Detailed description:
Stress and corticosteroid exposure are associated with changes in both the human and animal hippocampus. An extensive literature suggests that corticosteroid-induced changes in the hippocampus are, in part, mediated through increases in extracellular glutamate. In animals, agents that decrease glutamate release prevent dendritic changes in the hippocampus secondary to stress or corticosterone. We have developed a research program using patients receiving prescription corticosteroids (e.g., prednisone) to explore the effects of corticosteroids on the human hippocampus. Our research program is translational in focus, with a goal of exploring whether the reported effects of corticosteroids on the animal hippocampus are also found in humans. A current focus of our research is examining glutamate release inhibitors in patients taking corticosteroids. We have both open-label and placebo-controlled pilot data suggesting that the glutamate release inhibitor lamotrigine is associated with significant improvement in declarative memory (a measure of hippocampal performance) in this population. A definitive study examining declarative memory in corticosteroid-dependent patients receiving lamotrigine vs. placebo is proposed. Neuroimaging and mood will also be assessed.

Arms:
arm 1: Dose titration: begin at Baseline at 25mg PO QD for two weeks. Increase to 50mg PO QD at Week 2 for two weeks. Increase to 100mg PO QD at Week 4. Increase to 150mg PO QD at Week 5. Increase to 200mg PO QD at Week 6. Increase to 250mg PO QD at Week 7. Increase to 300mg PO QD at Week 8. Increase to 350mg PO QD at Week 9. Increase to 400mg PO QD at Week 10. Stay at 400mg PO QD from Week 10 to Week 48. arm 2: Placebo administered the same as the Lamotrigine just described.

Interventions: intervention 1: Lamotrigine intervention 2: Placebo
Intervention descriptions: intervention 1: Lamotrigine will be initiated at 25 mg/day and upwardly titrated to a dose of 400 mg/day over 10 weeks. intervention 2: None

Protocol document: