Memantine or Riluzole Prophylaxis for Corticosteroid-Induced Mood and Declarative Memory Changes

Twenty five (25) outpatients with pulmonary (e.g. asthma, cystic fibrosis) or rheumatic
(e.g. rheumatoid arthritis, dermatomyositis) illnesses scheduled to receive a brief course
(“burst”) of prednisone will be enrolled. The subjects will be randomized to receive
memantine, riluzole or placebo beginning immediately prior to the corticosteroid therapy and
continuing for one week. Measures of cognition and mood will be compared between the two
groups at baseline, day 3, and day 7.

Demographic information including age, gender, frequency and duration of prior
corticosteroid therapy and current anticipated dose and duration will be collected at
baseline. Baseline measures of mood will be assessed with the Activation subscale of the
Internal State Scale (ISS) (primary measure), Hamilton Depression Rating Scale (17-item
version), and Young Mania Rating Scale (YMRS). Cognition will be assessed with the RAVLT
(primary measure), Stroop, and Digit Span Backwards. The subjects will be given memantine
(10 mg), riluzole (50 mg), or identical appearing placebo 1 tablet daily for 3 days and then
at the first follow up appointment (day 3) the dose will be increased to BID if no side
effects are reported. The subjects will be reassessed twice, at day 3 and day 7. Mood and
cognitive measures will be repeated. The study visits will last approximately an hour and a
half. Participants will discontinue memantine when they discontinue prednisone. The RA
administering assessments will be blinded at all times. Alternative but equivalent versions
of the RAVLT and Digit Span Backwards will be given to minimize practice or learning
effects. Current and cumulative corticosteroid dose (mg each day X number of days) will be
determined and recorded.

HVLT-R test total words recalled scores will be compared between baseline and exit of the
active medication phase and placebo phase using a within subjects design and paired t-tests.
Based on our prior experience working with corticosteroid-dependent patients we have found
them to be very compliant with clinical treatment. Thus, we do not anticipate large numbers
of dropouts or missing data. In the case of missing data we will use the last observation
carried forward. In our lamotrigine study in a similar population, we found a change in
total words recalled on a word list and on the Stroop. Assuming a similar change with
memantine, using double-sided, paired t-tests, we could detect a difference with a change in
the placebo group with participants on the HVLT-R and up to with participants on the Stroop.
Thus, although this is primarily a pilot study to obtain effect sizes for future, larger
trials funded by NIH, it should have power to detect clinically meaningful differences
between medication and placebo.

Inclusion Criteria:

- 18-70 years old

- English speaking

- Able to provide informed consent

- Scheduled to receive a corticosteroid burst of at least 20 mg prednisone or
equivalent for at least 7 days

Exclusion Criteria:

- History of allergic reaction to memantine and/or riluzole

- Pregnant or nursing women

- History of liver disease, myocardial infarction, renal failure, diabetes with poor
glycemic control, or other unstable medical condition

- Mental retardation, dementia, or other severe cognitive disorder

- Prior prednisone therapy in the last 14 days

- Current alcohol/substance abuse/dependence