A Cochrane review [Abstract] 1 included 3 RCTs with a total of 577 patients with Parkinson's disease. One, larger trial (n=541) evaluated rivastigmine and two smaller trials (n=36) donepezil. For global assessment, these 3 trials comparing cholinesterase inhibitor treatment to placebo reported a difference in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) score of -0.38, favouring the cholinesterase inhibitors (95% CI -0.56 to -0.24, p<0.0001).There was evidence of a positive effect of cholinesterase inhibitors on the MMSE (WMD 1.09, 95% CI 0.45 to 1.73, p= 0.0008).
In larger rivastigmine trial, included in another Cochrane review [Abstract] 2 as an only trial, rivastigmine produced statistically significant improvements in several outcome measures. Rivastigmine was associated with a 2.80 point ADAS-Cog improvement (WMD -2.80, 95% Cl -4.26 to -1.34, p= 0.0002) and a 2.50 point ADCS-ADL improvement (95% Cl 0.43 to 4.57, p= 0.02) as compared with placebo. Clinically meaningful (moderate or marked) improvement occurred in 5.3% more patients on rivastigmine, and meaningful worsening occurred in 10.1% more patients on placebo. Significantly more patients on rivastigmine dropped out of the study due to adverse events (nausea, tremor, vomiting). Mortality was significantly lower in the rivastigmine group (4/362 vs. 7/179, OR 0.27, 95% CI 0.08 to 0.95, p=0.04).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, higher drop-out rate in the intervention group).
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