Real-World Data Links High-Blood Pressure Therapy With Parkinsonism, Researchers Report

Propranolol, a beta-blocker therapy for high-blood pressure, may be associated with an increased risk of developing parkinsonism — any condition that causes a combination of the movement abnormalities seen in Parkinson’s disease, according to a large database study.

Scientists also correlated five medications with a reduced risk of having Parkinson’s-like symptoms. These included medicines to promote wakefulness, and to treat attention deficit hyperactivity disorder.

The study, “Comprehensive Real-World Assessment of Marketed Medications to Guide Parkinson’s Drug Discovery,” was published in Clinical Drug Investigation.

Nowadays, medical data is routinely collected and stored in administrative healthcare databases. These databases comprise both patient health status, and delivery of healthcare-related information. People’s health information is found through electronic health records, medical claims, and drug and disease registries.

Since this information is collected outside the context of randomized trials, it provides real-world data based on the general population, and not so much on limited and controlled study samples. This enables scientists to draw more accurate conclusions on a given health intervention.

Providing a real-world perspective, administrative “healthcare databases have traditionally been used to monitor the safety of medications and for comparative effectiveness research,” the investigators said. Additionally, information from these databases is now being used to help in early drug development and drug repurposing.

The growing prevalence of Parkinson’s disease, disability, and deaths underlie the need for greater insight on real-world risk factors, the researchers said.

To find out more, scientists at Janssen Research and Development assessed the association of marketed medications with the risk of parkinsonism in four U.S. claims databases. Analyzed data sources included the IBM MarketScan Commercial Claims and Encounters (CCAE) database, IBM MarketScan Multi-State Medicaid Database (MDCD), IBM MarketScan Medicare Supplemental Database (MDCR), and Optum De-Identified Clinformatics Data Mart Database. In this study, analyzed subjects were their own controls.

The researchers assessed the possible associations between the use of 2,181 medications and a Parkinson’s diagnosis. Among the 117,015,066 individuals studied, 429,530 developed the neurodegenerative disorder.

The results showed that medications for promoting wakefulness, and for treating attention deficit hyperactivity disorder (ADHD), were associated with a reduced risk of parkinsonism.

The wakefulness medication armodafinil (brand name Nuvigil, among others) was associated with a 56% decrease in risk, while modafinil — with the brand name Provigil, among others — was linked to a 54% decrease. Methylphenidate, used to treat ADHD, under the brand name Ritalin, among others, was associated with a 39% decrease in the risk of having parkinsonism.

Research indicates Parkinson’s risk is somewhat related to the modulation of beta-adrenoreceptors. However, studies so far have failed to consistently demonstrate the exact contribution of the activation or inhibition of beta-adrenoreceptors. These are activated by a chemical messenger called epinephrine, a naturally circulating chemical that helps to regulate blood pressure.

For example, a beta-agonist called albuterol (brand name Ventolin, among others) has been linked to both a decreased and an increased risk of Parkinson’s disease. Researchers note that an agonist is a medicine that promotes the natural effect of a certain type of receptor, while a blocker antagonizes that same action.

In this real-world based study, individuals who took albuterol were 17% less likely to develop parkinsonism. On the other hand, of the three studied beta-blockers, only propranolol (brand name Inderal, among others) was correlated with a 32% increased risk of having Parkinson’s-like symptoms. Propranolol is used to treat high-blood pressure, atrial fibrillation, and tremors, among other conditions.

The results also found the antihistamine diphenhydramine (brand name Benadryl, among others), and the calcium channel blocker isradipine (brand names DynaCirc, Prescal), to be associated with a decreased risk of developing parkinsonism.

“These findings show association not causality,” the researchers said. Nonetheless, their findings support the association between beta-adrenoreceptors modulation and Parkinson’s risk.