Uses
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Alzheimer's Disease
Memantine hydrochloride is used for the palliative treatment of moderate to severe dementia of the Alzheimer's type (Alzheimer's disease). The current indication is based principally on 2 short-term (24 or 28 weeks) randomized, controlled clinical studies in adults (50-93 years of age) with a diagnosis of probable Alzheimer's disease that was moderate to severe. In both studies, patients treated with memantine hydrochloride received an initial dosage of 5 mg once daily, with weekly increases in increments of 5 mg daily until a dosage of 20 mg daily (10 mg twice daily) was reached. Patients enrolled in the 24-week study had received donepezil hydrochloride (a reversible acetylcholinesterase inhibitor) for at least 6 months (at a stable dosage for the preceding 3 months) and continued to receive donezepil hydrochloride in addition to either memantine hydrochloride or placebo during the study period. Various instruments were used to assess efficacy. In both studies, changes from baseline in cognitive performance were assessed using the Severe Impairment Battery (SIB) scale. Changes from baseline in overall daily function and overall clinical effects (including information from caregivers) were assessed using the modified Alzheimer's disease Cooperative Study Activities of Daily Living inventory (ADCS-ADL) and the Clinician's Interview Based Impression of Change (CIBIC plus), respectively. In both studies, patients receiving memantine hydrochloride experienced less deterioration in cognitive and daily function than patients receiving placebo. In the 24-week study, patients receiving memantine experienced less decline in CIBIC plus scores than patients receiving placebo; however, while improvements in CIBIC plus scores were observed in patients receiving memantine in the 28-week study, the difference from placebo (intent-to-treat analysis) was not statistically significant. In an unpublished 24-week open-label extension of the 28-week trial, improvement relative to the projected rate of continued decline in cognition, daily function, and overall clinical impression of change was observed in patients who were switched from placebo to memantine.
A third randomized, controlled clinical study of 12 weeks' duration was conducted in nursing home patients with severe dementia (Alzheimer's disease or vascular dementia). In patients randomized to receive memantine hydrochloride, therapy was initiated at a dosage of 5 mg once daily and increased to 10 mg once daily after one week. In this study, daily function was assessed using the care dependency subscale of the Behavioral Rating Scale for Geriatric Patients (BGP), and overall clinical effects were assessed using the Clinical Global Impression of Change scale (CGI-C); cognitive function was not evaluated. In a subset of patients diagnosed as having Alzheimer's disease, memantine hydrochloride was more effective than placebo, as assessed by changes from baseline in both the BGP and CGI-C scales.