The Efficacy of Licensed-Indication Use of Donepezil and Memantine Monotherapies for Treating Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: Systematic Review and Meta-Analysis

Abstract

Background/Aims: Behavioural and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD) greatly increase caregiver burden. The abilities of donepezil and memantine to manage BPSD within their licensed indications in AD were compared. Methods: A systematic review, random effects meta-analysis and Bucher indirect comparison were conducted. Results: Six randomised controlled studies (4 donepezil and 2 memantine) reported use within the licensed indication and had Neuropsychiatric Inventory (NPI) data suitable for meta-analysis. BPSD showed significant improvement with donepezil compared with placebo [weighted mean difference (WMD) in NPI –3.51, 95% confidence interval (CI) –5.75, –1.27], whereas this was not the case for memantine (WMD –1.65, 95% CI –4.78, 1.49). WMD in NPI for donepezil versus memantine favoured donepezil but was not statistically significant (–1.86, 95% CI –5.71, 1.99; p = 0.34). Conclusion: Within its licensed indication, donepezil is efficacious for the management of BPSD in AD compared with placebo.

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild‐to‐moderate Alzheimer's disease: a Bayesian network meta‐analysis

“…To our knowledge, this is the first NMA of ChEIs treatment in patients with AD in which compared using both direct and indirect comparisons of interventions across trials simultaneously. This should strengthen the findings from our analysis over previous meta‐analyses (Trinh et al , 2003; Birks, 2006; Hansen et al , 2008; Lockhart et al , 2011;Tan et al , 2014; Wang et al , 2014). The study quality of head‐to‐head trials might be questionable, because two out of three head‐to‐head trials were not double‐blinded.…”

“…Previous meta‐analyses have consistently demonstrated that ChEIs have beneficial effects on neuropsychiatric symptoms (Trinh et al , 2003; Hansen et al , 2008; Lockhart et al , 2011; Tan et al , 2014; Wang et al , 2014). However, differences in efficacy between each ChEI were inconsistent.…”

Pharmacological treatment of neuropsychiatric symptoms in Alzheimer's disease: a systematic review and meta-analysis

“…For memantine, one meta-analysis4 found that it improved behaviour symptoms while two4 6 did not demonstrate that. In addition, donepezil,4 galantamine5 and metrifonate7 were all proved to have significant effect on neuropsychiatric symptoms in early studies. However, in current meta-analysis, only galantamine was verified beneficial for neuropsychiatric symptoms.…”

Demographic and Neuropsychiatric Factors Associated With Off-label Medication Use in Frontotemporal Dementia and Alzheimer’s Disease

“…Deficits in cholinergic neurotransmission are believed to be central to the development of AD 7 and the efficacy of AChI for stabilizing cognitive function has been directly related to central effects on acetylcholinesterase function 8, 9 . However, patients with AD can also often develop behavioral impairments, such as agitation and irritability; often these are the most troublesome symptoms for the caregivers 10, 11 . There are no FDA approved drugs for behavioral and psychological symptoms in any dementias but there is often off-label use.…”

“…There are no FDA approved drugs for behavioral and psychological symptoms in any dementias but there is often off-label use. There is some evidence that donepezil and Memantine have some benefit on behavioral and psychological symptoms in AD 11,12 but often psychiatric medications including antipsychotics, antidepressants, and anxiolytics are used off-label to treat behavioral symptoms at all levels of disease severity 13, 14 .…”