Review: rivastigmine reduces rate of cognitive decline and improves performance in mild to moderate Alzheimer's.

Question: Is rivastigmine effective for the treatment of Alzheimer's disease? Outcomes: Cognitive function (measured by psychometric tests); dependency; global impression; functional performance; behavioural disturbance; quality of life; rates of institutionalisation; effect on carer; acceptability of treatment as measured by withdrawal from trials; adverse effects; death. Methods Design: Systematic review with meta-analysis. Data sources: The Specialised Register of the Cochrane Dementia and Cognitive Improvement Group (searched from date of inception to December 2005). The Cochrane Library, MEDLINE, PsycINFO, EMBASE, CINAHL and LILACS were searched for records added after December 2005 to March 2008; ongoing and other unpublished trials searched through Novartis, FDA, EMEA, NICE, Google and Copernic websites. Study selection and analysis: Randomised, double blind, placebo controlled trials of rivastigmine administered to patients with Alzheimer's disease or probable Alzheimer's disease (fulfilling DSM-IV or NINCDS-ADRDA) for more than 2 weeks. Exclusions: non-randomised trials; no allocation concealment. A single reviewer selected studies and assessed the quality of included trials on the basis of allocation concealment. Results from individual studies were combined and odds ratios were used to assess treatment effects for binary outcomes. Depending on the measure, continuous or ordinal variables were analysed either as a continuous change from baseline or as binary variables. A fixed effects model was used to estimate treatment effects unless there was significant heterogeneity (using the I2 statistic) where a random effects model was used. Intention to treat and completer analyses (using last observation varied forward) were performed. Main results Nine studies (n = 4775) met the inclusion criteria. Compared with placebo, high dose rivastigmine (6 -- 12 mg daily) improved cognitive function on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog, five studies; weighted mean difference (WMD) -1.99, 95% confidence interval (CI) -2.49 to -1.50 (intention to treat analysis)) and activities of daily living on the Progressive Deterioration Scale (four studies; WMD 2.15, 95% CI 1.13 to 3.16; (intention to treat analysis)) at 26 weeks. Lower dose rivastigmine (<=4 mg daily) led to significant improvements in cognitive function on ADAS-Cog, Mini-Mental State Examination and on global function. High dose rivastigmine was associated with significantly greater numbers of adverse events (nausea, vomiting, diarrhoea and abdominal pain, anorexia, headache, syncope and dizziness). One included study (added at the 2008 update) tested a rivastigmine transdermal patch (17.4 mg/day and 9.6 mg/day). The study found no difference in effectiveness between the two doses but the lower dose was associated with significantly fewer adverse events (nausea, vomiting, weight loss and dizziness). There was no difference between the 9.6 mg/day patch and 6 -- 12 mg/day oral capsules but the patch was associated with significantly fewer adverse events. Conclusions Rivastigmine (6 -- 12 mg) is effective for people with mild to moderate Alzheimer's disease and improves cognitive function, activities of daily living and severity of dementia. There is evidence from one trial that a low dose transdermal patch is associated with fewer adverse effects than the capsules and has comparable efficacy.