Combination Therapy With Memantine and Cholinesterase Inhibitors for Alzheimer’s Disease

Data analysis shows that combination treatment with memantine (MEM) (Namenda; Allergan, Madison, NJ) and cholinesterase inhibitors (ChEI) is more effective for treatment of neuropsychiatric symptoms in individuals with Alzheimer’s disease (AD) than ChEI alone. Using pooled data from 3 randomized-double blind placebo-controlled trials, the effect of MEM+ChEI vs ChEI on symptoms in 4 neuropsychiatric domains (psychosis, neurovegetative, frontal, and mood) was examined. The effects of treatment on these symptoms were measured with the neuropsychiatric inventory (NPI) at weeks 12 and 24. 

Mood symptoms including anxiety, depression/dysphoria, and apathy declined less for patients treated with MEM+ChEI compared with those treated with ChEI alone. For symptoms in the psychosis domain, including agitation/aggression, hallucinations, delusions, and irritability/lability, participants treated with MEM+ChEI had an average improvement of approximately 30% whereas those treated with ChEI alone had declines (P < .001). For neurovegetative symptoms, including appetite and eating changes, nighttime behavior, and aberrant motor behavior, treatment with MEM+ChEI resulted in significant improvement compared with ChEI alone (P = .0103). The difference in scores for the frontal domain was not significant, which may have been due to the very low scores in this domain at baseline (0.8 and 1.0 for those in the MEM+ChEI and ChEI alone, respectively. 

Data for this analysis came from 3 clinical trials. (Tariot et al. JAMA, 2004; Porsteinsson et al. Alzheimer Research, 2008; Grossberg et al. CNS Drugs, 2013). The 1,262 participants in the trials had a mean baseline NPI score of 14.9 ± 14.6 (moderate-to-mild AD, Mini Mental State Examination (MMSE) average score score 11.5 ± 3.5, and mean age 75.7 ± 8.3.