Can Prescription Drugs Alter the Risk for MS?

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Nerve cells are encased in a material called myelin. Myelin helps electrical impulses travel along nerves. Multiple sclerosis (MS) is a demyelinating disorder in which the body attacks the myelin sheaths of the brain and spinal cord causing patients with MS to experience visual disturbances, muscle weakness, cognitive problems, and so forth.

Like many illnesses, it’s believed that MS is influenced by environmental and genetic factors. In a December 2017 systematic review titled “Drug exposure and the risk of multiple sclerosis,” Yong and co-authors examine whether prescription drugs—an environmental factor—can influence the risk of MS. In this study, the researchers identified 13 high-quality studies for analysis. These 13 studies examined seven drug classes. Let’s take a look at the influence of each individual drug class on MS.

Amiloride

Amiloride (Midamor) is a potassium‐conserving diuretic used to treat hypertension or high blood pressure. Specifically, Midamor inhibits the acid-sensing ion channel 1 (ASIC‐1). In animal models of MS, ASIC-1 is upregulated, meaning that there is a cellular increase in ASIC-1. This cellular increase is found in regions of the central nervous system that have been damaged (i.e., plaques). In these animals, inhibition of ASIC-1 is shown to reduce neurodengeneration, a process associated with worsening disability in patients with MS.

Despite being effective at reducing demyelination in animals, Yong and colleagues found that there was no association between Midamor use and the frequency of MS in a Danish sample. (Denmark hosts extensive population-based registers, making it easier to do population-based studies examining public health.) Notably, this Danish sample comprised people who had late-onset MS, which the researchers defined as MS that developed in those aged 60 or more. Late-onset MS only affects 5 percent of people with MS; thus, it’s possible that these findings don’t apply to the greater MS population. In other words, it’s unknown whether Midamor influences the pathogenesis of MS in people who have MS but not late-onset MS.

On a related note, the researchers also found no influence of thiazide diuretics, which like Midamor are also used to treat high blood pressure, on MS.

Valproic Acid

Valproic acid (Valproic) is an anticonvulsant medication used to treat epilepsy. “Valproic acid inhibits histone deacetylase which can result in modification of specific proteins implicated in cell signaling and myelin repair,” write Yong and co-authors. Nevertheless, based on an analysis of Danish population-based data, the researchers found no association between Valproic and MS risk.

TNF Inhibitors

According to the American College of Rheumatology, "TNF inhibitors are a type of drug used worldwide to treat inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis, juvenile arthritis, inflammatory bowel disease (Crohn’s and ulcerative colitis), ankylosing spondylitis, and psoriasis. They reduce inflammation and stop disease progression by targeting an inflammation-causing substance called Tumor Necrosis Factor (TNF)."

Yong and co-authors once again looked at Danish population-based studies to figure out whether there was an association between TNF inhibitors and MS. Both of the studies examined were observational and involved cohorts or population samples that were followed over time.

Yong and colleagues found no association between treatment with TNF inhibitors for inflammatory bowel disease and the development of MS. Specifically, although there was a fourfold increase in the risk of developing MS in those taking TNF inhibitors for inflammatory bowel disease, this rise was no different from the fourfold risk that people with inflammatory bowel disease already exhibit for demyelinating events like MS.

The researchers did find, however, that men receiving TNF inhibitors for arthritis and men and women receiving TNF inhibitors for ankylosing spondylitis were at greater risk for MS after initiating treatment. Of note, ankylosing spondylitis is more common in men.

One limitation of the Danish studies examined is that it was unclear which types of TNF inhibitors were used, and different types of TNF inhibitors affect inflammation in different ways.

According to the Yong and co-authors: "Combined, preliminary observations raise concern over the safety of anti‐TNFα [TNF inhibitors] with respect to MS risk, but more work is needed. It would also be of value to ascertain if any effects are product specific or generalizable to the whole therapeutic class.”

Antibiotics

Two case-control studies—one in the UK and the other in Denmark—examined the association between antibiotic use and MS. A case-control study compares patients who have an outcome or disease (i.e., cases) with those who don’t (i.e., controls). With case-control studies, researchers look back retrospectively to determine exposure to risk factors. In the UK and Danish studies, the cases involved patients who were diagnosed with MS, and the risk factor of interest was antibiotic use.

In the UK study, 163 patients with MS were matched with 1523 people without MS based on age, sex, and other factors. The researchers found that overall antibiotic use was not associated with MS. However, either penicillin use for more than two weeks or tetracycline use for more than one week was associated with a 50 percent reduced risk of MS.

Danish researchers tried to replicate the findings of the UK researchers using a larger sample size (3259 cases). Interestingly, the Danish researchers found that a wide range of antibiotic uses was associated with elevated risk of MS—even in patients taking only one course of antibiotics for seven days.  The fact that a broad range of antibiotic use was associated with MS seems to suggest that the actual infection itself—not the antibiotics themselves—was linked to the development of MS.   

Overall, it appears that antibiotics are not associated with MS in most analyses, but more research needs to be done.

Inhaled Short‐acting Beta2‐adrenergic Receptor Agonists

The drugs fenoterol (Berotec N) and salbutamol (ProAir HFA) are both inhaled short-acting beta2-adrenergic receptor agonists used to treat asthma and chronic obstructive pulmonary disease. In a population-based case control study, Taiwanese researchers examined whether these drugs influenced MS risk. They found that although there was a reduced risk of MS in those taking Berotec N, the risk of developing MS was not associated with ProAir HFA.

The Taiwanese researchers suggested that Berotec N may exert a protective effect because of its superior ability to inhibit superoxide generation and degranulation. Apparently, ProAir HFA is not as good as doing these things; thus, it exerts no protective effect.  

Furthermore, when considering short-acting beta2-adrenergic receptor agonists as a class, Yong and co-authors state the following: “The short‐acting beta2‐adrenergic agonists are bronchodilators that inhibit interleukin‐12, a cytokine that drives T cell differentiation towards proinflammatory T helper 1 cells.” Of note, experts suggest that T cells (a type of white blood cell) play an important role in the damage of myelin sheaths that leads to MS.

Antihistamines

Using a case-control design, UK researchers examined whether sedating and non-sedating antihistamines were associated with the development of MS. Factors such as allergic disease (e.g., asthma, eczema, and hay fever) and smoking were adjusted for. The researchers found that although non-sedating antihistamines were not associated with MS risk, sedating antihistamines were associated with an 80 percent reduced risk of developing MS.

Researchers suggested that the reason why sedating antihistamines could somehow exert a protective effect is that—unlike non-sedating antihistamines—these drugs cross the blood-brain barrier and exert some nonspecific effect on the brain and spinal cord.

Oral Contraceptives

Yong and colleagues analyzed five studies that looked for an association between the use of oral contraceptives and MS risk. Overall, there was no association between these two variables.

More Info About Multiple Sclerosis

Multiple sclerosis is characterized by selective destruction of myelin in nerve cells of the central nervous system (brain and spinal cord). It does not affect nerve cells located in the peripheral nervous system (i.e., nerves and ganglia located outside the brain and spinal cord). This disease is autoimmune, which means that the body attacks itself.

Besides prescription drugs, which have only more recently gained recognition as a possible etiologic factor, other causative factors have been implicated in the pathogenesis of MS including the following:

Worldwide, MS affects 2.5 million people, and in the United States, more than 400,000 people are with the disease.

The onset of MS may be either abrupt or gradual. Initial symptoms may be so subtle that a person with MS may not even notice them for months or years. Here are some symptoms of MS:

  • Weakness
  • Sensory symptoms
  • Visual disturbances
  • Troubles with gait and coordination
  • Urinary urgency
  • Urinary frequency
  • Fatigue
  • Motor difficulties

These symptoms can wax and wane, with recurrent attacks lasting weeks or months followed by some degree of recovery. Symptoms can be made worse by heat, fatigue, exercise, or stress.

Ultimately, MS is a diagnosis of exclusion, which means that it’s only diagnosed after other possible illnesses, such as spinal cord tumors or acute disseminated encephalomyelitis (secondary to infection), are ruled out. When diagnosing MS, history and physical exam findings as well as MRI findings are helpful. Changes in biomarkers in the cerebrospinal fluid are also observed.

Unfortunately, there is no cure for MS. However, there are treatments available, including corticosteroids and plasma exchange for the treatment of acute flare-ups, as well as several disease-modifying therapies such as beta interferons for the prevention of new MS lesions.

A Word From Verywell

Keep in mind that this systematic review by Yong and co-authors is the first to examine the influence of various drugs on MS. The results of this systematic review are meant to shed light on the pathogenesis of MS—a disease we still don’t understand the causes of.

At this point, no clinician would use these findings to direct treatment. Any information derived from this systematic review needs to be confirmed and replicated. If you are taking any of these medications and are concerned about how they influence MS risk, feel free to discuss what you learned with your prescribing physician. However, don’t discontinue (or start taking) medications based on what you read in this article—and without input from your physician.

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