Researchers may have discovered why certain tremors and asthma medications increase the risk of developing Parkinson’s disease.
Their findings suggest they were caused by the underlying clinical indications that led physicians to prescribe these medications in the first place — tremors and smoking-related lung conditions — rather than the medications themselves.
Their study, “β2-adrenoreceptor medications and risk of Parkinson disease,” appeared in the journal Annals of Neurology.
A previous study, using mouse models and nationwide pharmacy data from Norway, suggested that using therapies that target the beta-2 adrenoreceptor — which is found in cells of the lung, brain, heart, skeletal muscle, and immune system — can influence the risk of developing Parkinson’s.
That study suggested that medications known to suppress the beta-1 receptor — such as propranolol, a first-line treatment for tremors — doubled the risk of Parkinson’s, while those known to activate the receptor —such as salbutamol, usually given to treat asthma and other lung diseases — decreased the risk by a third.
Researchers at Washington University School of Medicine in St. Louis, Missouri, have now evaluated whether the underlying clinical indications for the use of these medications – tremors and lung conditions – could explain these associations.
Their hypothesis was based on the fact that tremors are among the early signs of Parkinson’s, and that lung disease is more frequent in smokers than non-smokers, with several studies suggesting a link between nicotine and a lower risk of Parkinson’s.
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The team analyzed the Medicare data of 28,295 U.S. Parkinson’s patients and 52,324 healthy individuals. They evaluated the effects that three medications which block the beta-2 receptor (propranolol, carvedilol, and metoprolol) and primidone (used to treat tremors) or of salbutamol and inhaled corticosteroids used for similar lung conditions — had on the risk of developing Parkinson’s.
They found that use of propranolol prior to Parkinson’s diagnosis appeared to triple risk of the disease, while use of primidone boosted the risk nine-fold. Meanwhile, the use of carvedilol and metoprolol was linked to a slightly decreased risk of Parkinson’s.
However, when researchers adjusted the data for the presence or absence of tremors, or for the use of these medications 18 months before Parkinson’s diagnosis, or when the analysis was restricted to patients with tremors, propranolol and primidone were shown to have minimal effect.
“Our results suggest that the onset of tremor in … [Parkinson’s pre-diagnostic] period may lead to propranolol use, and thereby a positive association with PD [Parkinson’s disease],” researchers wrote.
The fact that propanol and primidone – which do not suppress the beta-2 receptor – showed similar trends before and after adjustments further supports the non-association of medications that block beta-2 receptors with the risk of Parkinson’s.
The team also believes the results for carvedilol and metoprolol may be explained by their infrequent use by U.S. physicians to treat tremors.
Similarly, while salbutamol and inhaled corticosteroids were long thought to reduce the risk of Parkinson’s, the adjustment for smoking attenuated these associations, especially for salbutamol, for which the risk became close to null.
These findings highlight that, despite previous suggestions, medications that target beta-2 receptors do not appear to change the risk of developing Parkinson’s.
“We cannot completely rule out the possibility that there could be some effect of these medications, but it is clear that if any effect exists it is much smaller than previously reported,” researchers wrote, noting that they’d need additional studies with “even greater ability to adjust for smoking and to lag medication exposures” in order to confirm these results.