(150) Associations between β-adrenoreceptors agonists and antagonists and Parkinson’s disease: systematic review and meta-analysis

Background: β-blockers and β-agonists are among the most prescribed drugs worldwide. Recent studies suggested an association between propranolol and Parkinson’s disease (PD), prompting a signal procedure at the safety committee of the European Medicines Agency. This study aimed to systematically review, critically appraise, and meta-analyse the studies that provided evidence on the association between use of β-blockers (including propranolol) and use of β-agonists, and risk of PD.

Methods: We searched Embase, Medline, and Clinicaltrials.gov up to March 2023. Two reviewers screened the records and extracted the data. The risk of bias was assessed through important domains in pharmacoepidemiology studies. The restricted maximum likelihood method was used to compute pooled effect estimates and 95% confidence intervals (CIs); heterogeneity was calculated with the I-squared statistic. Subgroup analyses explored sources of heterogeneity.

Results: Eighteen studies were eligible. The summary relative risk (RR) of PD was 1.41 (95%CI: 1.04-1.09) for β-blockers (10 studies) and 0.86 (0.78-0.94) for β2-agonists (6 studies). Among specific β-blockers, the summary RR of PD was 2.36 (1.59-3.50) for propranolol (7 studies), 0.84 (0.80-0.88) for carvedilol (3 studies) and 0.99 (0.91-1.07) for metoprolol (4 studies). For specific β-agonists, summary RR was 0.88 (0.79-0.99) for salbutamol, 0.92 (0.86-0.98) for short acting beta-agonists and 0.82 (0.71-0.94) for long-acting beta agonists. Twelve of the 16 studies of β-blockers had a moderate or high risk of protopathic bias, as propranolol may be used to treat tremor. Control for confounding by smoking (a protective factor against PD) was deficient or lacking in 13/18 studies.

Conclusion: Evidence on a positive association between β-blockers and Parkinson’s disease is likely explained by protopathic bias and confounding. Further studies are warranted to explore the potential protective effect of β-agonists.