Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis

Abstract

BackgroundThis is the first meta-analysis to compare the treatment effects and safety of administering donepezil alone versus a combination of memantine and donepezil to treat patients with moderate to severe Alzheimer Disease, particularly regarding cognitive functions, behavioral and psychological symptoms in dementia (BPSD), and global functions.MethodsPubMed, Medline, Embase, PsycINFO, and Cochrane databases were used to search for English and non-English articles for inclusion in the meta-analysis to evaluate the effect size and incidence of adverse drug reactions of different treatments.ResultsCompared with patients who received donepezil alone, those who received donepezil in combination with memantine exhibited limited improvements in cognitive functions (g = 0.378, p < .001), BPSD (g = −0.878, p < .001) and global functions (g = −0.585, p = .004). Gradual titration of memantine plus a fixed dose and gradual titration of donepezil as well as a fixed dose and gradual titration of memantine resulted in limited improvements in cognitive functions(g = 0.371, p = .005), BPSD(g = −0.913, p = .001), and global functions(g = −0.371, p = .001).ConclusionBoth in the 24th week and at the final evaluation point, the combination of donepezil and memantine led to greater improvement in cognitive functions, BPSD, and global functions than did donepezil alone in patients with moderate to severe Alzheimer Disease.

Long-Term Effects Of Combined Treatment With Memantine And Donepezil On Alzheimer's Disease Patients: 72-Week Study

“…Previous studies have also indicated that when the course of the disease progresses to moderate or severe levels, combination treatments are more effective than single treatment for delaying the degradation of cognitive functions [12,14,[15][16][17][18][19][20][21][22]. Further, we have reported that memantine administered to patients with moderate to severe AD may inhibit the reduction of cerebral blood flow in the prefrontal area, improve global clinical symptoms, cognitive function and BPSD, and lighten the burden of care placed on caretakers [23].…”

“…In the evaluation of global symptoms, there was a significant interaction between the Control and Combination groups in CGI-I (F = 37.67 (1,22), p < 0.001). Regarding cognitive function, there was significant interaction between the Combination group and the Control group in MMSE (F = 9.39 (1,22), p = 0.01) and in CDT (F = 15.84 (1,22), p < 0.001) (Figure 2).…”

“…Regarding BPSD assessment, there was significant interaction between the Combination and Control groups in NPI (F = 47.76 (1,22), p < 0.001). A significant difference between the Combination and Control groups in the item-by-item NPI score was observed in delusion, hallucination, agitation, depression and dysphoria, anxiety, inaction and apathy, disinhibition, irritability and instability, and abnormal behavior (Figure 3).…”

“…In the care burden assessment, there was significant interaction between the Combination and Control groups in J-ZBI (F = 18.91 (1,22), p < 0.001). A significant difference was observed in 3 out of 22 sub-items of J-ZBI (Figure 4).…”

“…Regarding cognitive function, there was significant interaction between the Combination group and the Control group in MMSE (F = 9.39 (1,22), p = 0.01) and in CDT (F = 15.84 (1,22), p < 0.001) (Figure 2). …”