A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease.
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.


OBJECTIVE
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.
Department of Clinical Pharmacology, St. Vincent's Hospital, Melbourne, Australia.
S
S
Scharf
A
A
Mander
A
A
Ugoni
F
F
Vajda
N
N
Christophidis
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D003071:Cognition; D004008:Diclofenac / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D016595:Misoprostol / Q000627:therapeutic use*; D010919:Placebos; D013997:Time Factors; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010919:Placebos; D016595:Misoprostol; D004008:Diclofenac