A Cochrane review «»1 «Rolinski M, Fox C, Maidment I et al. Cholinesteras...»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 «»2 «Maidment I, Fox C, Boustani M. Cholinesterase inhi...»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).