Efficacy and tolerability of rivastigmine in patients with dementia of the Alzheimer type

Rivastigmine is a new pseudo-irreversible carbamate inhibitor of acetylcholinesterase (AChE), A single 3-mg oral dose of rivastigmine inhibits AChE in the central nervous system for 6 to 10 hours, with minimal inhibition of enzyme in the periphery, The present study investigated the efficacy and tolerability of two different dosages of rivastigmine (4 and 6 mg/d) in elderly patients with probable Alzheimer's disease. Significantly more patients treated with rivastigmine 6 mg/d compared with placebo experienced a successful outcome according to scores on the Clinical Global Impression of Change Scale (42.72% vs 29.91%), Performance on the Digit Symbol Substitution test and storage and retrieval on the Fuld Object-Memory Evaluation test were also significantly better in patients receiving rivastigmine (4 or 6 mg/d) compared with placebo, Both dosages of rivastigmine were well tolerated, with superior tolerability at the lower dose level. Patients, investigators, and caregivers rated the tolerability of active treatment either generally "very good" or "good." No statistically significant or clinically relevant drug-related changes were found in any vital signs, hematologic variables, or liver or kidney function. Rivastigmine appears to be effective in the treatment of patients with probable Alzheimer's disease and is well tolerated at a dosage of 6 mg/d, The low incidence of adverse events and good tolerability seen in this study suggest that higher daily doses of rivastigmine could be used in future trials, possibly leading to enhanced efficacy relative to that demonstrated in this preliminary study.