Memantine in severe dementia: results of the9M-best study (benefit and efficacy in severly demented patients during treatment with memantine)

OBJECTIVES: To assess clinical efficacy and safety of memantine--an uncompetitive N-methyl-D-aspartate (NMDA) antagonist--in moderately severe to severe primary dementia. MATERIALS AND METHODS: Dementia was defined by DSM-III-R criteria and severity was assessed by the Global Deterioration Scale (stages 5-7) and the Mini-Mental State Examination (< 10 points). Primary endpoints were the Clinical Global Impression of Change (CGI-C) rated by the physician, and the Behavioural Rating Scale for Geriatric Patients (BGP), subscore 'care dependence', rated by the nursing staff. Secondary endpoints included the modified D-Scale (Arnold/Ferm). RESULTS: The ITT sample comprised 166 patients and 151 patients were treated per protocol. At 12-week ITT endpoint analysis, 82 received memantine 10 mg per day, 84 placebo. Dementia was in 49% of the Alzheimer type and in 51% of the vascular type (CT, Hachinski score). A positive response in the CGI-C was seen in 73% versus 45% in favour of memantine (stratified Wilcoxon p < 0.001), independent of the etiology of dementia. The results in the BGP subscore 'care dependence' were 3.1 points improvement under memantine and 1.1 points under placebo (p = 0.016). A coincident response of the two independent target variables was observed in 61.3% (memantine) versus 31.6% (placebo). Secondary endpoint analysis of the D-Scale assessing basic ADL functions support the primary results. Regarding the safety profile, no significant differences between treatment groups were observed. CONCLUSIONS: The results of this trial support the hypothesis that memantine treatment leads to functional improvement and reduces care dependence in severely demented patients.