A 5-month, randomized, placebo-controlled trial of galantamine in AD

Objective: To investigate the efficacy and tolerability of galantamine, usi ng a slow dose escalation schedule of up to 8 weeks, in 978 patients with m ild to moderate AD. Methods: A 5-month multicenter, placebo-controlled, dou ble-blind trial. Following a 4-week placebo run-in, patients were randomize d to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cog nitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician's Inte rview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychi atric Inventory. Standard safety evaluations and adverse event monitoring w ere carried out. Results: After 5 months, the galantamine-placebo differenc es on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for t he 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with pl acebo, the galantamine 16- and 24-mg/day groups also had a significantly be tter outcome on CIBIC-plus, activities of daily living, and behavioral symp toms. Treatment discontinuations due to adverse events were low in all gala ntamine groups (6 to 10%) and comparable with the discontinuation rate in t he placebo group (7%). The incidence of adverse events in the galantamine g roups, notably gastrointestinal symptoms, was low and most adverse events w ere mild. Conclusions: Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with p lacebo. Slow dose escalation appears to enhance the tolerability of galanta mine, minimizing the incidence and severity of adverse events.