The PREDICT-PD Blog: Salbutamol and PD risk

Recently at one of our movement disorders meeting we began to discuss whether people with PD should be prescribed salbutamol. Salbutamol is a drug that has been used to treat asthma and COPD (a smoking related breathing disorder) for a long time. There has been lots of interest in Salbutamol because in epidemiological studies it appears to be protective against developing PD.

Salbutamol works by activating a receptor called the beta-adrenergic receptor which in turn causes the airways to expand; making it easier to breath. There are also medications that do the opposite of this, block the beta-adrenergic receptor. Examples of these medications are bisoprolol, atenolol, propanolol and metoprolol. Interestingly these medications regularly come up as risk factors for PD in similar studies. So based on this data; medications which block the beta-adrenergic receptor increase the risk of PD and medications which activate the beta-adrenergic receptor protect people against PD. This has the potential to be a critical finding as it would mean clinicians may have a simple medication which could prevent Parkinson’s disease.

Unfortunately the link between the beta receptor and PD may not be as clear as these studies imply. There are a number of other possible explanations and confounders. As I mentioned earlier is used to treat Asthma and COPD, COPD is a lung disease that is almost exclusively found in smokers. Smoking is known to be associated with a decreased risk of PD. Therefore people who are prescribed salbutamol are much more likely to smoke and subsequently more likely to develop PD. So that could potentially explain why the beta agonists appear to protect people from PD but then why do beta-blockers seem to increase the risk of PD? One of the earliest symptoms of PD is a tremor and patients are often misdiagnosed initially as having an essential tremor. The treatment for essential tremor involves a beta-blocker called propanolol or metoprolol. So it is possible that people with early Parkinson’s disease are mistakenly being prescribed beta-blockers so in studies they appear to increase the risk of PD.

A recently published case-control study from Denmark has explored some of these associations. First of all they found again that people with PD are much less likely to take beta-agonists. But they found two key things that indicate that this relationship is driven by smoking rather than beta-agonists. First of all the same reduced odds ratio for PD was found for all medications used to treat COPD in smokers such as anti-cholinergics and inhaled steroids. All of these medications are much more likely to be prescribed in smokers indicating  that beta-agonists are not having a special effect on PD. Also the same reduction in odds ratio for PD was found for people who had been prescribed beta-agonists regardless of the duration of beta-agonist use. The same reduced odds ratio was seen even for people who had been prescribed beta-agonists within the past year which is very unlikely to be having a disease modifying effect on PD as the neurodegeneration typically occurs over years.

With regard to beta-blockers they found that short term beta-blocker prescriptions had a much stronger association with PD than long term beta-blocker prescriptions. This suggests that the association is much more likely to be driven by early PD symptoms being mistaken for essential tremor rather than beta blockers actually causing PD. Also, interestingly, they only found the association for beta-blockers used for treating tremor (such as propanolol and metoprolol) but they did not find an association with other beta blockers such as bisoprolol which can not be used to treat tremor.

This is a really fascinating study which provides important information about the link between beta-adrenergic medication and PD. The data indicates that all of the PD protective effects of beta-agonists are actually mediated by smoking and the risk of beta-blockers is accounted for by attempts to treat the early symptoms of PD.

Neurology. 2019 Jul 9;93(2):e135-e142.
doi: 10.1212/WNL.0000000000007694. Epub 2019 May 24.
Use of
β2-adrenoreceptor agonist and antagonist drugs and risk of Parkinson disease.
Hopfner F1Wod M1Höglinger GU1Blaabjerg M1Rösler TW1Kuhlenbäumer G1Christensen K1Deuschl G1Pottegård A2.

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