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Evidence summaries

Rivastigmine for Alzheimer's Disease

Rivastigmine appears to be slightly effective in mild to moderate Alzheimer's disease in terms of cognitive function, activities of daily living and global assessment. Level of evidence: "B"

The quality of evidence is downgraded by indirectness of evidence (short follow-up, surrogate outcomes).

A treatment attempt with rivastigmine is recommended for improving cognitive function, activities of daily living and global assessment.in Alzheimer's disease.

The recommendation is strong because of possible positive effect on patient important outcomes such as cognitive function, activities of daily living and global assessment. The cost of rivastigmine is low.

A Cochrane review [Abstract] 1 included 7 studies with a total of 3450 subjects with mild to moderate Alzheimer's disease (AD). The mean age was about 75 years. The trials had a duration of between 12 and 52 weeks. The main analysis compared the safety and efficacy of rivastigmine 6 to 12 mg/day orally or 9.5 mg/day transdermally with placebo. After 26 weeks of treatment rivastigmine compared to placebo was associated with better outcomes for cognitive function measured with the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score (MD -1.79; 95% CI -2.21 to -1.37; 6 studies, n = 3232) and MMSE score (MD 0.74; 95% CI 0.52 to 0.97; 6 studies; n = 3205), activities of daily living (SMD 0.20; 95% CI 0.13 to 0.27; 6 studies, n = 3230) and clinician rated global impression of changes, with a smaller proportion of patients treated with rivastigmine experiencing no change or a deterioration (OR 0.68; 95% CI 0.58 to 0.80; 7 studies, n = 3338).Three studies reported behavioural change, and there were no differences compared to placebo (SMD -0.04; 95% CI -0.14 to 0.06; 3 studies, n = 1529). Only one study measured the impact on caregivers using the Neuropsychiatric Inventory-Caregiver Distress (NPI-D) scale and this found no difference between the groups (MD 0.10; 95% CI -0.91 to 1.11; 1 study, n = 529). Overall, participants who received rivastigmine were about twice as likely to withdraw from the trials (OR 2.01, 95% CI 1.71 to 2.37; 7 studies, n = 3569) or to experience an adverse event during the trials (OR 2.16, 95% CI 1.82 to 2.57; 7 studies, n = 3587).Most side effects were described as mild and occurred during titration period. Gastrointestinal symptoms were the most common.

A NICE systematic review [PubMed] 2 included 4 published and 2 unpublished RCTs with a total of 1940 subjects who had mild to moderate AD. The mean ages of the subjects were between 68 and 75 years and the study durations between 13 to 26 weeks. 3 published RCTs reported ADAS-cog and the baseline scores were statistically similar (21,7 to 24). 1 RCT showed no statistical difference between treatments. A meta-analysis of the two other RCTs showed an improvement between rivastigmine 1-4 mg and placebo of 1.16 points (95 % CI 1.87 to 0.46) and between rivastigmine 6-12 mg and placebo of 3.08 points (95 % CI 3.78 to 2.38).

Clinical comments

Although the clinical benefits in the included studies were small, a treatment attempt is warranted due to the debilitating nature of the disease and its impact on the patient's quality of life.

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Primary/Secondary Keywords