beta-adrenoreceptors and the risk of Parkinson's disease

Hopfner, Franziska; Höglinger, Gunter U.; Kuhlenbaeumer, Gregor; Pottegard, Anton; Wod, Mette; Christensen, Kaare; Tanner, Caroline M. und Deuschl, Gunther (2020): beta-adrenoreceptors and the risk of Parkinson's disease. In: Lancet Neurology, Bd. 19, Nr. 3: S. 247-254

Abstract

Background: beta-adrenoceptors are widely expressed in different human organs, mediate important body functions and are targeted by medications for various diseases (such as coronary heart disease and heart attack) and many beta-adrenoceptor acting drugs are listed on the WHO Model List of Essential Medicines. beta-adrenoceptor antagonists are used by billions of patients with neurological disorders, primarily for the treatment of migraine and action tremor (mainly essential tremor), worldwide. Recent developments An observational study reported a link between the chronic use of the beta-adrenoceptor antagonist propranolol and an increased risk of Parkinson's disease, while the chronic use of the beta-adrenoceptor agonists was associated with a decreased risk. Further support of this association was provided by a dose-dependent decrease in the risk of Parkinson's disease with chronic beta-adrenoceptor agonist (eg, salbutamol) use, and by functional data indicating a possible underlying molecular mechanism. Five additional epidemiological studies have examined the modulation of the risk of Parkinson's disease as a result of the use of beta-adrenoceptor-acting drugs in different populations. Overall, similar estimates but different interpretations of the associations were provided. Several findings suggest that the increase in risk of Parkinson's disease associated with beta-adrenoceptor antagonists use can be explained by reverse causation because prodromal Parkinson's disease is often associated with non-specific action tremor, which is usually treated with propranolol. The lower risk of Parkinson's disease seen in patients receiving beta-adrenoceptor agonists is likely to be indirectly mediated by smoking because smoking has a strong inverse association with Parkinson's disease (people that smoke have a reduced risk of developing Parkinson's disease). Smoking also causes chronic obstructive pulmonary disease, which is treated with beta-adrenoceptor-agonist medications. Even if causal, the effect of beta-adrenoceptor antagonists on the risk of Parkinson's disease would be small compared with other Parkinson's disease risk factors and would be similar to the risk evoked by pesticide exposure. The estimated risk of Parkinson's disease because of beta-adrenoceptor antagonists use corresponds to one case in 10 000 patients after 5 years of propranolol use, and would be considered a very rare adverse effect. Thus, not using beta-adrenoceptor antagonists would severely harm patients with recommended indications, such as heart disease or migraine. Similarly, 50 000 people would have to be treated for 5 years with salbutamol to prevent Parkinson's disease in one patient, suggesting that primary preventive therapy studies on disease modification are not warranted. Where next? Epidemiological evidence for a causal relationship between use of beta 2-adrenoceptor antagonists and the increased risk of Parkinson's disease is weak, with other explanations for the association being more probable. Future observational studies are warranted to clarify this association. However, given the very low risk associated with propranolol, most clinicians are unlikely to change their treatment approach.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1474-4422
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198