Data analysis, prescriptions trends and the risk of Parkinson’s disease
It is incredibly important when taking any medication(s) to be aware of potential interactions with other drugs or supplements you may also be taking. It can be confusing, especially if you’re taking more than one medication and/or dealing with more than one ailment or disease for which you are taking medications, which is often the case for people living with Parkinson’s disease (PD). Almost every medication out there has some sort of side-effect, limitation, or caution to consider, so it is important for you to educate yourself and ask questions of your medical team.
Prescription medications to avoid if you have Parkinson’s
There are many drugs to be avoided in PD because they block dopamine receptors and can increase the slowness, stiffness and balance problems of PD. There are also drugs that interact with particular PD medications, specifically monoamine oxidase B inhibitors (such as selegiline, rasagiline and safinamide) and need to be avoided by people taking those particular medications. Both of these groups of medications are listed in APDA’s Medications to Avoid educational supplement.
In addition to these two groups of medications, many medications have side effects that need to be considered in the context of PD. Because people with PD may be particularly prone to certain non-motor symptoms, they may be more sensitive to particular medication side effects such as fatigue, confusion, low blood pressure or constipation, among others. For example, particular medications for anxiety or sleep could potentially cause gait unsteadiness and would need to be used with caution in those with balance and gait difficulties. For all of these reasons, it is important to periodically review all of your medications with your doctor.
Medications that have been associated with development of Parkinson’s
In addition to the categories of medications listed above, there are other medications that may need particular consideration for those with PD because some studies have shown certain drugs to be associated with the development of PD.
That is, observations have been made that indicate that certain medications (which are not used to treat PD) are more likely to have been prescribed to people with PD or to people who subsequently develop PD than to people who do not have or do not develop PD. These pharmacologic trends definitely raise some eyebrows and beg the question – could these medications contribute to an increased risk of PD? Or, can the prescription patterns be explained in another way?
Often these findings are reported in the media and people with PD who are on these medications do not know what to do. Should I stop taking the medication? Did this medication cause my PD? The short answer is to discuss any concern that you have about your medications with your doctor. As is often the case, these situations are not always clear cut or easy to explain, so we will delve into these issues a bit more in today’s blog.
Two recent examples of the above scenario are the potential association of PD with the use of oral antibiotics and the use of beta blockers.
Antibiotics, your microbiome, and Parkinson’s
A recent article published in the medical journal Movement Disorders analyzed 13,976 cases of PD in Finland (as compared to 40,697 controls without PD) and analyzed their prescription records, assessing the association between prior antibiotic exposure and PD. The strongest association with PD risk was found with oral exposure to macrolides (azithromycin and related antibiotics) and lincosamides (clindamycin and related antibiotics). The increased risk of PD was not large – for those exposed to these antibiotics, risk of PD was 1.4 times that of those who did not have exposure to these antibiotics. Exposure to other antibiotics had a smaller increased risk.
The authors hypothesize that alteration in gut microbiome caused by antibiotics may influence the development of PD. (Inflammation, gut microbiome and PD were topics addressed in previous blogs). Although this is an intriguing possibility, this hypothesis is far from proven. Many other hypotheses are equally as possible and could be suggested for the association. For example, perhaps a particular infection (for which the antibiotic is given), increases the PD risk and there is no direct association between the antibiotic itself and PD.
It is also important to note that antibiotics are considered one of the most important developments in the history of modern medicine, almost solely responsible for a massive increase in life expectancy from the beginning of the 20th century until now. Those who are prescribed oral antibiotics to treat a pneumonia or urinary tract infection, for example, must take their antibiotic to return to health.
So although prescription records note a small increased risk of PD associated with oral antibiotic use, we do not know whether the antibiotic itself increases PD risk, or something that the antibiotic use is associated with is the culprit, such as a particular infection. And we do know that infections can be deadly and need to be treated. All in all, it remains prudent to take your antibiotics when prescribed.
It is true however, that there has been a tendency among some physicians to over-prescribe antibiotics, perhaps in order to placate demanding patients, for conditions such as viral infections that do not respond to antibiotics. This tendency has led to the development of antibiotic resistance (the development of bacteria that are no longer eliminated by antibiotics that once killed them) which is a major threat to public health. Antibiotic resistance in turn requires the use of even more powerful antibiotics which further leads to more resistance. For this reason, (and not for the prevention of PD!), prudent prescribing practices of antibiotics is crucial.
Beta blockers and increased risk of Parkinson’s — causation or correlation?
A number of papers have investigated prescribing trends of beta adrenergic antagonist medications (commonly known as beta blockers) and their relationship to PD. Beta blockers work by blocking the beta adrenergic receptor and are primarily used to treat high blood pressure. However, they are also used to treat tremor, which complicates matters, as we will discuss below.
A paper from one of APDA’s Centers for Advanced Research at Brigham and Women’s Hospital in Boston, and authored by a member of APDA’s Scientific Advisory Board, Dr. Clemens Scherzer, analyzed prescription trends in Norway and demonstrated that propranolol, a beta blocker, was associated with an increased risk of PD whereas, salbutamol, a beta agonist (which stimulates the beta adrenergic receptor) used in the treatment of asthma, was associated with a decreased risk of PD. Interestingly, they also showed that the beta-adrenergic receptor regulates alpha-synuclein, a key component of Lewy bodies that accumulate in PD. This suggests a potential link between beta blocker use and development of PD.
The finding that beta blockers (particularly propranolol) and beta agonists were associated with an increased and decreased risk of PD respectively, was repeated in another study, utilizing health records in Israel. In this study, the group carefully controlled for many variables that could explain the association between beta blockers and PD, including a prior diagnosis of essential tremor, and still found that propranolol was associated with an increased risk of PD.
Another paper, also from one of APDA’s Centers for Advanced Research — this one at Washington University in St Louis, came to a different conclusion. This research group analyzed Medicare data in the US to discern the risk of PD in relation to use of beta blockers and beta agonists. Whereas propranolol was associated with an increased PD risk as was found in the Norwegian and Israeli studies, when this was adjusted for tremor prior to PD diagnosis, the association disappeared, suggesting that people with PD may be prescribed beta blockers early in their disease course as a way to control tremor.
Yet another paper analyzed a large data set, this one in Denmark, to determine the association between beta blockers and beta agonists. Its conclusions were aligned with the paper that analyzed Medicare data — that PD symptoms of tremor triggered the prescription of beta blockers and not the reverse.
These competing papers demonstrate the difficulties inherent in this type of research and more research is necessary to sort out the effects of beta blockers on PD risk. At this juncture, there is not enough information to instruct PD patients either to stop their beta blocker (or to add a beta agonist).
With large databases of medical records available for analysis, epidemiological studies such as the ones described above have become more feasible. But although analyzing large amounts of data can be very helpful in revealing patterns, trends and associations, proving causation – that one element of the data causes another – is much harder to do. This means that associations that are identified in epidemiological studies need to be further studied more directly in clinical trials. So while we welcome any advancing of our understanding of potential risk factors of PD, we need to carefully consider what it means practically for PD care.
Tips and takeaways
- Some medications have side effects or interactions with other drugs that are important for people with PD to be aware of. People with PD also need to be aware of how certain medications can affect them specifically because of their PD symptoms.
- Large epidemiological studies have been performed to try to identify trends or associations between prescribing patterns of certain medications and rates of PD.
- Oral antibiotics and beta blockers have been identified in this manner as associated with an increased risk of PD.
- Despite this association, antibiotics are critical for people fighting infection so you should talk to your doctor if you have concerns about taking antibiotics that have been prescribed to you.
- Large epidemiological studies can be tricky to analyze and different studies can reach different conclusions.
- Proving an association however, does not prove causation, and more direct study of the link must be undertaken.
- Discuss any concerns that you have about your medications with your neurologist.