Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial

Objectives To assess the effects of rivastigmine on the core domains of Alz heimer's disease. Design Prospective, randomised, multicentre, double blind, placebo controll ed, parallel group trial. Patients received either placebo, 1-4 mg/day (low er dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine. Doses wer e increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day) ove r the first 12 weeks with a subsequent assessment period of 14 weeks. Setting 45 centres in Europe and North America. Participants 725 patients with mild to moderately severe probable Alzheimer 's disease diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the criteria of the National Institut e of Neurological and Communicative Disorders and Stroke and the Alzheimer' s Disease and Related Disorders Association. Outcome measures Cognitive subscale of the Alzheimer's disease assessment s cale, rating on the clinician interview based impression of change incorpor ating caregiver information scale, and the progressive deterioration scale. Results At the end of the study cognitive function had deteriorated among t hose in the placebo group. Scores on die Alzheimer's disease assessment sca le improved in patients in the higher dose group when compared with patient s taking placebo (P < 0.05). Significantly more patients in the higher dose group had improved by 4 points or more than had improved in the placebo gr oup (24% (57/242) v 16% (39/238)), Global Function as rated by the clinicia n interview scale had significantly improved among tl-lose in the higher do se group compared with those taking placebo (P < 0.001), and significantly more patients in the higher dose group showed improvement than did in the p lacebo group (37% (80/219) v 20% (46/230)). Mean scores on the progressive deterioration scale improved From baseline in patients in the higher dose g roup but fell in the placebo group. Adverse events were predominantly gastr ointestinal, of mild to moderate severity, transient, and occurred mainly d uring escalation of the dose. 23% (55/242) of those in the higher dose grou p, 7% (18/242) of those in the lower dose group, and 7% (16/239) of those i n the placebo group discontinued treatment because of adverse events. Conclusions Rivastigmine is well tolerated and effective. It improves cogni tion, participation in activities of daily living, and global evaluation ra tings in patients with mild to moderately severe Alzheimer's disease. This is the first treatment to show compelling evidence of efficacy in a predomi nantly European population.