FPIN’s Help Desk Answers

Alzheimer Disease: Monotherapy vs. Combination Therapy ELISABETH LAWLER, MD, and AMBER AVILA, MD, Southern Illinois University School of Medicine Family Medicine Residency Program, Springfield, Illinois

Help Desk Answers pro- Clinical Question pooled results of all three studies found no dif- vides answers to questions submitted by practicing Is the combination of memantine with ference between combination and monother- family physicians to the donepezil more effective in the treatment apy. A subgroup analysis limited to patients Family Physicians Inquiries of Alzheimer disease than either drug alone? with moderate to severe dementia found a Network (FPIN). Members small but significant cognitive improvement of the network select Evidence-Based Answer questions based on their with combination therapy compared with relevance to family medi- Combination treatment with memantine and donepezil alone (standard mean difference = cine. Answers are drawn donepezil results in a small improvement in 0.45; 95% confidence interval, 0.27 to 0.63). from an approved set of cognitive function that is of uncertain clini- There was no significant benefit with combi- evidence-based resources and undergo peer review. cal significance in patients with moderate to nation therapy in the study of patients with The strength of recom- severe Alzheimer disease, but no improvement mild to moderate dementia. mendations and the level in patients with mild to moderate disease. A retrospective cohort study investigated of evidence for individual studies are rated using (Strength of Recommendation: B, based on a the combination of memantine and a cholin- criteria developed by the meta-analysis­ of randomized controlled trials.) esterase inhibitor compared with a cholines- Evidence-Based Medicine terase inhibitor alone.2 The study included Working Group (http:// Evidence Summary 240 patients with Alzheimer disease who were www.cebm.net/?o=1025). A meta-­analysis of three double-blind ran- older than 60 years and had been treated The complete database domized controlled trials evaluated the use with a cholinesterase inhibitor for at least of evidence-based ques- of combination therapy with memantine plus six months. Initially, 117 patients received tions and answers is copyrighted by FPIN. If donepezil (two studies) or memantine plus donepezil, 110 received rivastigmine, and 13 interested in submit- donepezil, galantamine, or rivastigmine in received galantamine. Memantine was then ting questions or writing patients with Alzheimer disease.1 Data were added to the regimen and titrated to a target of answers for this series, go to http://www.fpin. analyzed for 1,043 patients diagnosed with 20 mg per day at four weeks. Baseline MMSE org or e-mail: questions@ likely Alzheimer disease based on the National scores were compared with scores at three and fpin.org. Institute of Neurological and Communicative six months of combination therapy. There This series is coordinated Disorders and Stroke and the Alzheimer’s was a minimal yet significant improvement in by John E. Delzell Jr., MD, Disease and Related Disorders Association MMSE scores between month 3 and month 6 MSPH, Assistant Medical criteria or Mini-Mental State Examination (14.58 to 14.74; paired t-test; P < .02). Editor. (MMSE). The two studies of memantine plus Copyright Family Physicians Inquiries Network. Used with A collection of FPIN’s Help donepezil included patients with moderate to permission. Desk Answers published in severe Alzheimer disease. One study included AFP is available at http:// Address correspondence to Amber Avila, MD, at aavila@ www.aafp.org/afp/hda. patients with mild to moderate dementia. siumed.edu. Reprints are not available from the authors. Patients receiving monotherapy (cholinester- Author disclosure: No relevant financial affiliations. ase inhibitor alone [two studies] or meman- tine alone [one study]) were compared with REFERENCES those using a combination of a cholinesterase 1. Muayqil T, et al. Systematic review and meta-analysis of inhibitor plus either memantine or placebo. combination therapy with cholinesterase inhibitors and Patients were followed for 24 to 52 weeks. memantine in Alzheimer’s disease and other dementias. Post-therapy cognitive outcomes were mea- Dement Geriatr Cogn Dis Extra. 2012;​2(1):​546-572. sured using the MMSE, the Alzheimer’s Dis- 2. Gareri P, et al. Retrospective study on the benefits of combined Memantine and cholinEsterase inhibitor treat- ease Assessment Scale–Cognitive Subscale, or Ment in AGEd Patients affected with Alzheimer’s disease. the Severe Impairment Battery. Analysis of J Alzheimers Dis. 2014;41(2):​ 633-640​ . ■

452 American Family Physician www.aafp.org/afp Volume 95, Number 7 ◆ April 1, 2017