OBJECTIVE: To investigate the efficacy and tolerability of galantamine,
using a slow dose escalation schedule of up to 8 weeks, in 978 patients with
mild to moderate AD.
METHODS: A 5-month multicenter,
placebo-controlled, double-blind trial. Following a 4-week placebo run-in,
patients were randomized 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 cognitive subscale of the AD Assessment Scale (ADAS-cog), the
Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus),
the AD Cooperative Study Activities of Daily Living inventory, and the
Neuropsychiatric Inventory. Standard safety evaluations and adverse event
monitoring were carried out.
RESULTS: After 5 months, the
galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day
group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo,
both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups
also had a significantly better outcome on CIBIC-plus, activities of daily
living, and behavioral symptoms. Treatment discontinuations due to adverse
events were low in all galantamine groups (6 to 10%) and comparable with the
discontinuation rate in the placebo group (7%). The incidence of adverse
events in the galantamine groups, notably gastrointestinal symptoms, was low
and most adverse events were mild.
CONCLUSIONS: Galantamine 16 and 24
mg/day significantly benefits the cognitive, functional, and behavioral
symptoms of AD as compared with placebo. Slow dose escalation appears to
enhance the tolerability of galantamine, minimizing the incidence and severity
of adverse events.