Level 2: Mid-level evidence
Galantamine (Razadyne, previously Reminyl) is used to treat mild-to-moderate Alzheimer’s disease (AD). A previously published systematic review of 10 randomized, double-blind, placebo-controlled trials concluded that galantamine 16 mg daily improved global and cognitive symptoms for at least six months in mild-to-moderate AD (Cochrane Database Syst Rev. 2006;:CD001747). Trials lasted at least four weeks and included 6,805 patients with AD or mild cognitive impairment (MCI). In eight of the trials, significant effects were reported for global ratings, cognitive tests, and assessments of activities of daily living and behavior in patients with mild-to-moderate disease. Galantamine doses of 16-36 mg/day were associated with significant effects in trials that lasted three to six months; there were no significant differences with doses of 8 mg/day. Adverse effects were dose-related and similar to those of other cholinesterase inhibitors. In two trials of patients with MCI, galantamine was associated with marginal clinical benefit and unexplained excess mortality.
A new study took a different approach to defining outcomes, using goal attainment to distinguish efficacy. The Video-Imaging Synthesis of Treated Alzheimer’s Disease (VISTA) trial evaluated 130 patients with mild-to-moderate AD who were randomized to galantamine or placebo for four months; 109 patients (84%) completed the controlled phase of the trial (CMAJ. 2006;174:1099-1105, full text available online free of charge at http://www.cmaj.ca/cgi/content/full/174/8/1099, accessed November 7, 2006). The initial galantamine dose of 4 mg twice daily for four weeks was increased to 8 mg twice daily for four weeks and then to 16-24 mg/day based on tolerability. Outcomes evaluated consisted of up to six personalized goals defined by patients and caregivers and by clinicians. There were no significant differences in goal attainment based on ratings completed by patients and caregivers; 23% of patients receiving galantamine vs. 30% of those receiving placebo did not meet any of their goals. Galantamine was associated with a modest increase in clinician-rated goal-attainment scores (29% vs. 47% met none of clinician-set goals). Dementia of moderate severity was present in 27% of patients receiving galantamine compared with 39% receiving placebo, which may present bias against galantamine as patients with moderate dementia achieved better goal attainment scores.