Five case-control studies (n=11,570 participants) and two cohort studies (n=289,850 participants) were included in the review, with an additional four studies included in sensitivity analyses (two were excluded from the review because they did not report separate results for different anti-inflammatory drugs, and two were excluded as the anti-inflammatory drug use was within one year of Parkinson's disease diagnosis).
The incidence of Parkinson's disease was reduced in people who used non-aspirin NSAIDs (RR 0.85, 95% CI 0.77 to 0.94; I2=0%; seven studies). Subgroup analyses assessing the effects of duration and intensity of use indicated a dose-response relationship. Subgroup analysis based on sex indicated similar results amongst men and women. Subgroup analysis indicated that ibuprofen had a stronger effect (RR 0.75, 95% CI 0.64 to 0.89; three studies) than for all non-aspirin NSAIDs. Sensitivity analysis based on exposure status indicated a larger effect in studies that assessed prescription and over-the-counter use, rather than just prescription use. Sensitivity analyses omitting one study at a time did not significantly alter the results.
There was no significant difference in the incidence of Parkinson disease between people who used aspirin and those who did not (six studies); there was evidence of significant heterogeneity for this result. There was an increase in the incidence of Parkinson disease amongst men who used aspirin (RR 1.22, 95% CI 1.03 to 1.44), but not women. Sensitivity analyses omitting one study at a time did not significantly alter the results.
There was no significant difference in the incidence of Parkinson disease between people who used acetaminophen and those who did not (two studies).
Results of the sensitivity analyses, including the studies excluded from the review based on exposure ascertainment, were similar but there was greater heterogeneity.
The funnel plot did not indicate the presence of publication bias.