Double-blind, placebo-controlled study of metrifonate, an acetylcholinesterase inhibitor, for Alzheimer disease.
Fifty patients with probable Alzheimer disease (AD) completed a 3-month double-blind study to compare metrifonate to placebo. We dosed metrifonate to achieve a 40-60% inhibition of red blood cell acetylcholinesterase activity. The Alzheimer Disease Assessment Scale cognitive subscale score (ADAS-C) served as the primary outcome measure. At the completion of 3 months of treatment, the metrifonate group ADAS-C score differed significantly from the placebo group score by 2.6 points (p < 0.01). A 0.75-point trend toward improvement occurred during treatment in the ADAS cognitive performance of the metrifonate group (p = 0.15), and a 1.10-point deterioration in cognitive performance was found in the placebo group (p < 0.02). On the Global Improvement Scale (GIS), the two groups differed significantly on their changes from baseline to treatment phase (p < 0.02). Significant deterioration occurred in GIS scores (p < 0.01) and in Mini Mental State Examination (MMSE) scores (p < 0.03) in the placebo-treated group. Adverse effects were uncommon and did not require adjustment of the dose of metrifonate or discontinuation of treatment. We achieved a mean of 52.3% decrease in red blood cell acetylcholinesterase activity. During up to 18 months of subsequent open metrifonate treatment of patients, we found a deterioration of 1.68 points per year in MMSE performance. These findings support further study of the effects of metrifonate on deterioration rate in AD.
Becker
R E
RE
Department of Psychiatry, Southern Illinois University School of Medicine, Springfield 62794-9230, USA.
Colliver
J A
JA
Markwell
S J
SJ
Moriearty
P L
PL
Unni
L K
LK
Vicari
S
S
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014236:Trichlorfon / Q000009:adverse effects / Q000627:therapeutic use*
D002800:Cholinesterase Inhibitors; D014236:Trichlorfon