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From the Department of Clinical Pharmacology (Dr. Scharf), St. Vincent’s Hospital, Melbourne; Grace McKellar Center (A. Mander), Geelong; Department of General Practice and Public Health (A. Ugoni), University of Melbourne; Australian Center for Clinical Neuropharmacology (Dr. Vajda), St. Vincent’s Hospital, Melbourne; and Department of Clinical Pharmacology (Dr. Christophidis), St. Vincent’s Hospital, Melbourne, Victoria, Australia.
Address correspondence and reprint requests to Dr. S. Scharf, Aged Care Services, Caulfield General Medical Centre, 294 Kooyong Road, Victoria, 3162, Australia.
BACKGROUND: Previous studies suggest a potential benefit from nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer’s disease (AD). Prescribing NSAIDs, however, carries the risk of significant gastrointestinal adverse events.
OBJECTIVES: To study whether treatment with an NSAID prevents expected decline in AD patients and evaluate whether co-administration of the gastro-protective agent, misoprostol, with an NSAID is safe in AD.
METHODS: The efficacy and safety of diclofenac in combination with misoprostol (D/M) was evaluated in 41 patients with mild-moderate AD in a prospective 25-week, randomized, double-blind placebo-controlled trial. Efficacy measures comprised the Alzheimer’s Disease Assessment Scale cognitive and noncognitive subsections, Global Deterioration Scale, Clinical Global Impression of Change, Mini-Mental State Examination, Instrumental Activities of Daily Living, Physical Self-Maintenance Scale, and a caregiver-rated Global Impression of Change.
RESULTS: There were no group differences with any of the outcome measures in an intent-to-treat analysis. There were some nonsignificant trends for the placebo group to have deteriorated more than the D/M-treated patients. Withdrawal rates were 12 of 24 in the D/M group and 2 of 17 in the placebo group. There were no serious drug-related adverse events.
CONCLUSIONS: This pilot study, with small treatment numbers, did not demonstrate a significant effect of NSAID treatment in AD, but the trends observed justify further investigations with a larger number of participants. D/M is safe in AD patients, but its tolerability is not optimal.
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