FPIN's Help Desk Answers
Alzheimer Disease: Monotherapy vs. Combination Therapy
Am Fam Physician. 2017 Apr 1;95(7):452.
Is the combination of memantine with donepezil more effective in the treatment of Alzheimer disease than either drug alone?
Combination treatment with memantine and donepezil results in a small improvement in cognitive function that is of uncertain clinical significance in patients with moderate to severe Alzheimer disease, but no improvement in patients with mild to moderate disease. (Strength of Recommendation: B, based on a meta-analysis of randomized controlled trials.)
A meta-analysis of three double-blind randomized controlled trials evaluated the use of combination therapy with memantine plus donepezil (two studies) or memantine plus donepezil, galantamine, or rivastigmine in patients with Alzheimer disease.1 Data were analyzed for 1,043 patients diagnosed with likely Alzheimer disease based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria or Mini-Mental State Examination (MMSE). The two studies of memantine plus donepezil included patients with moderate to severe Alzheimer disease. One study included patients with mild to moderate dementia. Patients receiving monotherapy (cholinesterase inhibitor alone [two studies] or memantine alone [one study]) were compared with those using a combination of a cholinesterase inhibitor plus either memantine or placebo. Patients were followed for 24 to 52 weeks. Post-therapy cognitive outcomes were measured using the MMSE, the Alzheimer's Disease Assessment Scale–Cognitive Subscale, or the Severe Impairment Battery. Analysis of pooled results of all three studies found no difference between combination and monotherapy. A subgroup analysis limited to patients with moderate to severe dementia found a small but significant cognitive improvement with combination therapy compared with donepezil alone (standard mean difference = 0.45; 95% confidence interval, 0.27 to 0.63). There
1. Muayqil T, et al. Systematic review and meta-analysis of combination therapy with cholinesterase inhibitors and memantine in Alzheimer's disease and other dementias. Dement Geriatr Cogn Dis Extra. 2012;2(1):546–572.
2. Gareri P, et al. Retrospective study on the benefits of combined Memantine and cholinEsterase inhibitor treatMent in AGEd Patients affected with Alzheimer's disease. J Alzheimers Dis. 2014;41(2):633–640.
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