SAN DIEGO — Use of memantine in patients with moderate to severe Alzheimer's disease significantly reduced their behavioral disturbances and psychiatric symptoms, compared with placebo, Jeffrey L. Cummings, M.D., reported in a poster session at the annual meeting of the American Association for Geriatric Psychiatry.
“We think this represents an important, newly recognized benefit for the use of memantine in patients with Alzheimer's disease,” Dr. Cummings, director of the University of California, Los Angeles, Alzheimer's Disease Research Center, said in an interview. “The question we posed was, does a drug like memantine, which is used for cognitive improvement, have any effect on agitation? What we saw was that in several analyses—whether we looked at week 12 or week 24, whether we looked at patients who were asymptomatic at baseline or symptomatic at baseline—memantine reduced agitation.”
For the 24-week study, Dr. Cummings and his associates randomized 403 patients at 37 clinical centers who had moderate to severe Alzheimer's disease to receive either memantine 10 mg b.i.d. or placebo. The memantine was titrated up weekly in 5-mg increments from a starting dose of 5 mg/day during week 1 to 20 mg/day at week 4. All patients remained on donepezil throughout the study.
The investigators used the Neuropsychiatric Inventory (NPI) to assess behavioral symptoms at baseline, week 12, and week 24.
Of the 403 community-dwelling patients, 202 received memantine and 201 received placebo. The mean age of study participants was 76 years, and 65% were female. Most (91%) were white.
When compared with patients in the placebo group at 12 weeks, those in the memantine group had significant improvements on the NPI domains of agitation/aggression (-0.4 vs. 0.2), irritability/lability (-0.4 vs. 0.1), and appetite/eating change (-0.4 vs. 0.1), where a negative value denotes improvement and a positive value signifies worsening of symptoms. Improvements in all of these NPI domains remained statistically significant at 24 weeks.
“I was surprised by the magnitude and consistency of the effect,” Dr. Cummings told CLINICAL NEUROLOGY NEWS.
The investigators also observed that in patients who were asymptomatic at baseline, memantine treatment resulted in significantly less emergence of agitation/aggression and appetite/eating changes by week 24, compared with those on placebo.
According to Dr. Cummings, this is the first study to look at the effect of memantine on behavior in Alzheimer's disease.
Forest Laboratories Inc., manufacturer of memantine, supported the study.