Research

Reversing Corticosteroid-Induced Memory Impairment

Purpose

The purpose of this study is to determine if lamotrigine is associated with greater improvement in declarative memory than placebo in patients receiving prescription corticosteroids. We will also examine if lamotrigine is associated with greater improvement in working memory and other cognitive domains, and mood symptoms than placebo.

Project Summary

The study is open to all English-speaking men and women age 18-70 years. The patients must be taking at least 5 mg of prednisone or prednisolone, or at least 4 mg of methylprednisolone for at least 6 months, with anticipated treatment for at least another 15 months.

The duration of the study is 60 months, with appointments every 2 weeks for the first 12 weeks, and then once every 12 weeks until week 60. The patients will be given various mood, memory, and health assessments during the study.

The study also includes two MRI scans, and as such patients with metal implants close to the head or claustrophobia will not be good candidates for the study. Participants must not have a history of mood disorders such as depression, bipolar disorder, and schizophrenia that is unrelated to corticosteroid use.

Moreover, any conditions involving the central nervous system including multiple sclerosis, brain tumor, and seizures, and a lifetime history of drug and alcohol dependence are exclusions for the study. We encourage all patients to call the researchers to be screened for the study criteria.

Background

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.

Frequently Asked Questions

Q: Is compensation available for participation in the study?
A: Yes, patients will be paid for each visit in the study. Patients will also be paid for the successful completion of MRI scans for baseline and week 48 visits.

Q: Is transportation available for the study appointments?
A: Yes. DART passes will be provided for each study visit to cover transportation costs.