An observational study reported a link between the chronic use of the β-
adrenoceptor antagonist
propranolol and an increased risk of
Parkinson's disease, while the chronic use of the β-
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 β-
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 β-
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 β-
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 β-
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 β-
adrenoceptor-agonist medications. Even if causal, the effect of β-
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 β-
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 β-
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 β2-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.