Patients with AD benefit from stabilised symptoms, as they are able to remain at a higher check details functional level for longer [1]. Caregivers also benefit from reduced patient decline as the patient’s retained independence reduces the burden placed upon the caregiver. In the present study, since patients in the placebo group were already receiving stable donepezil treatment, the addition of memantine offered extra benefits by further reducing the occurrence of marked clinical worsening, not just in later stages, but also in moderate AD. Safety and tolerability In moderate to severe AD, and moderate AD, combination treatment with memantine and donepezil was well-tolerated and had a similar incidence of AEs as treatment with placebo added to donepezil.

Individually, studies MEM-MD-02 and MEM-MD-12 indicated that combination therapy with memantine added to donepezil/ChEI was safe and well-tolerated [16,17], a pattern of safety that was also recently reported in the DOMINO-AD study [35]. In the present study, the frequency of agitation was approximately half in the memantine-treated group compared with the placebo-treated group. A significant reduction in the incidence of agitation in favour of memantine monotherapy over placebo has been previously observed in a meta-analysis of patients with AD [31]. Furthermore, in a pooled analysis of patients with moderately severe to severe AD (MMSE 3 to 14) who had baseline symptoms of agitation/aggression or psychosis, a significantly greater proportion of memantine-treated patients experienced an improvement of agitation/aggression over 6 months than patients treated with placebo [39].

AE profiles from previous studies also suggest that memantine administration may be associated with amelioration of gastrointestinal AEs Carfilzomib typically associated with ChEI use, and that rates of diarrhoea and faecal incontinence may be reduced when memantine is added to stable donepezil reference 4 treatment [16,40]. Strengths of study This study includes data from rigorous 24-week RCTs in the largest population of moderate to severe patients treated with the combination of memantine/placebo added to donepezil considered to date (510 participants in the ITT set). The two studies included in the meta-analyses had similar inclusion/exclusion criteria, and by further restricting the MMSE range to 5 to 19 and the allowed baseline ChEI to donepezil 10 mg/day, the subjects included produced much more homogeneous groups of patients in which potential signals of efficacy could be detected. Calculation of effect sizes in this study also allows for comparisons within and between studies and to gauge the magnitude of clinical effects/clinical significance, not just statistical significance.