Table 1.
Results of randomized controlled trials in moderate to severe Alzheimer’s disease
| Study | Number of patients (treatment/placebo) | Mean MMSE at baseline | Follow-up | Outcomes measures | Main conclusion | References |
|---|---|---|---|---|---|---|
| MEM-MD-01 (memantine vs placebo) | 178/172 | 10 | 24 wks | SIB, NPI, ADCS-ADLsev CIBIC+, BGP BGP-care, FAST | Significant advantage with Memantine on the SIB and CIBIC+ at 12 and 18 weeks, but no significant difference at 24 wks | van Dyck et al24 |
| MEM-MD-02 (memantine plus donepezil vs placebo plus donepezil) | 203/201 | 10 | 24 wks | ACDS-ADLsev CIBIC+, SIB, NPI, BGP-care | Memantine plus donepezil showed significant benefits in all measures compared to placebo plus donepezil | Tariot et al23 |
| Post-hoc analysis of responders: MEM-MD-02 | ACDS-ADLsev CIBIC+, SIB, NPI | Responder analyses show an NNT of 8–10, and memantine produces both clinically important improvement and stabilization of symptoms | van Dyck et al41 | |||
| Post-hoc analysis of cognitive effects: MEM-MD-02 | SIB | Beneficial cognitive effects on memory, language, and praxis with memantine treatment | Schmitt et al42 | |||
| Post-hoc analysis of behavioral effects: MEM-MD-02 | NPI | Memantine reduced agitation/aggression, irritability, and appetite/eating disturbances | Cummings et al43 | |||
| Post-hoc analysis of functional outcome: MEM-MD-02 | ADCS-ADL | Memantine showed benefits on function with grooming, toileting, conversing, watching TV, and being left alone | Feldman et al44 | |||
| Memantine vs placebo | 126/126 | 8 | 28 wks | ACDS-ADLsev CIBIC+, SIB, NPI, MMSE, FAST, GDS | Memantine had better outcome on ACDS-ADL, CIBIC+ and SIB | Reisberg et al22 |
| 24-wk open-label extension of the 28-wk RCT | 52 wks | ACDS-ADLsev CIBIC+, SIB, NPI, MMSE, FAST, GDS | Patients who switched from placebo to memantine had improvements in all efficacy measures (relative to rate of decline in placebo phase) | Reisberg et al36 | ||
| Post-hoc analysis of functional disability in the 28-wk RCT | 28 wks | ACDS-ADLsev | Memantine-treated patients were 3 times more likely to remain autonomous | Rive et al40 | ||
| Post-hoc health economic analysis of the 28 wk RCT | 28 wks | RUD | Resource utilization and total health costs were lower in the memantine treated group | Wimo et al39 | ||
| 9M-Best study (memantine vs placebo) | 82/84 | 6 | 12 wks | CGI-C, BPG, BPG-care, Ferm’s D-scale | Significant improvement in CGI-C and BPG favoring memantine treatment | Winblad and Poritis21 |
Abbreviations: ADCS-ADLsev, Alzheimer’s Disease cooperative Study Activities of Daily Living Scale – a modified version for severe AD patients; BGP (BPG-care), Behavior Rating Scale for Geriatric Patients (BPG-care = BPG-care dependency subscale); CGI-C, Clinical Global Impression-change; CIBIC+, Clinician’s Interview Based Impression of Change with caregiver input; FAST, Functional Assessment Staging Tool; GDS, Global Deterioration Scale; MMSE, Mini Mental State Examination; NPI, Neuropsychiatric Inventory; RUD, Resource Utilization in Dementia scale; SIB, severe impairment battery.