Hidden risks of these common daily medications

By Naveed Saleh, MD, MS
Published November 9, 2020

Key Takeaways

Every day, millions of Americans chase a handful of prescription pills with a glass of water. The older you are, the more pills you’re likely to use. For instance, 75% of people between ages 50 and 64 years take prescription drugs compared with 91% of those aged 80 years and older. The mean number of prescriptions filled per year also rises with age, with an average of 13 filled in those aged 50-64, and 22 in those aged 80 years and older.

“The great majority of adults who have one of five common chronic conditions—diabetes, heart disease, hypertension, arthritis, and cancer—use prescription drugs,” according to the Health Policy Institute at Georgetown University. “For example, 89 percent of people with arthritis and 98 percent of people with diabetes use prescription drugs. People with these conditions fill many prescriptions annually and have significant prescription drug expenditures. Adults with diabetes fill about 4 times as many prescriptions and spend about 4 times as much on prescription drugs as the general population. High prescription drug use may also reflect the fact that people have multiple chronic conditions.”

With so many Americans taking prescription drugs, particularly for chronic conditions, it’s worth considering the impact. Though deemed mostly safe, long-term use of medications can cause certain adverse effects. Here are six medications taken long-term that can cause problems.

Antidepressants

Major depression can be chronic, thus maintenance therapy can prevent relapse or recurrence. Maintenance on antidepressants can last anywhere from 6 months after remission to life, depending on factors such as remission of symptoms and risk. While patients are on antidepressants, adverse effects must be managed, as well as the implementation of strategies to combat partial and nonresponse to therapies.

Taking antidepressants long-term is linked to negative side effects, as highlighted in a study published in Patient Preference and Adherence. In the study, although 89.4% of 180 survey respondents noted that long-term antidepressant use improved their mood, repercussions included withdrawal (73.5%), sexual problems (71.8%), weight gain (65.3%), emotional numbness (64.5%), and dependence (43%).

In the general population, antidepressant use may also impact heart health, with use increasing the risk of heart attack and stroke by 14%, per the results of a meta-analysis spanning 17 studies published in Psychotherapy and Psychosomatics. In cardiovascular patients, however, the risk of new cardiovascular events was unchanged, according to the study.

PPIs

Proton-pump inhibitors (PPIs) are big business, with their outpatient use doubling between 1999 and 2012, raking in more than $11 billion annually in the process.

These drugs are approved long-term for gastroesophageal reflux disease (GERD) prevention/symptom control, Barrett esophagus, prophylaxis against bleeding induced by nonsteroidal anti-inflammatory drugs (NSAIDs), and pathologic hypersecretory conditions like Zollinger-Ellison syndrome.

More recently, concerns have arisen over the long-term safety of these drugs. 

“Although PPIs have had an encouraging safety profile, recent studies regarding the long-term use of PPI medications have noted potential adverse effects, including risk of fractures, pneumonia, Clostridium difficile diarrhea, hypomagnesemia, vitamin B12 deficiency, chronic kidney disease, and dementia,” according to the authors of a review published in Mayo Clinic Proceedings.

“These emerging data have led to subsequent investigations to assess these potential risks in patients receiving long-term PPI therapy. However, most of the published evidence is inadequate to establish a definite association between PPI use and the risk for development of serious adverse effects. Hence, when clinically indicated, PPIs can be prescribed at the lowest effective dose for symptom control,” they concluded.

Aspirin

Aspirin increases the risk of fatal and non-fatal bleeding. Fortunately, in those who need long-term aspirin therapy, certain protective steps can be taken. 

In the United States and Europe, between 40% and 66% of adults aged 75 years or older take daily aspirin or other antiplatelet agents, with half taking these drugs for secondary prevention, as recommended by evidence-based guidelines. 

For those on aspirin therapy, PPIs can lower the risk of bleeding by 70% to 90%. But concomitant prescription of PPIs is low due to concerns over adverse effects.

Per the authors of a prospective population-based cohort study published in The Lancet, “In patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper gastrointestinal bleeding.”

They advised, “Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal, the estimated NNT [number needed to treat] for routine PPI use to prevent such bleeds is low, and co-prescription should be encouraged.”

Skeletal muscle relaxants

In an attempt to avert opioid burden, clinicians have turned to skeletal muscle relaxants (SMR). The prescription of these drugs doubled between 2005 and 2016, according to the results of a nationally representative cross-sectional analysis of office visits published in JAMA Network Open. But just because SMRs are not opioids doesn’t mean they’re without risk. Disquieting trends in prescription patterns of these drugs include administration to the elderly, prescription for long-term use, and co-administration with opioids. Importantly, long-term use of these drugs is linked to certain adverse effects.

“Carisoprodol, chlorzoxazone, cyclobenzaprine, methocarbamol, metaxalone, and orphenadrine are all considered potentially inappropriate medications in older adults, in whom these agents are associated with sedation, cognitive impairment, and fracture,” the authors wrote. ”An additional concern regarding the inappropriate use of SMRs is the potential for drug-drug interactions, particularly with opioids.”

Corticosteroids

Glucocorticoids are used long-term to treat chronic inflammatory diseases—including asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease—as well as Graves disease, rheumatic diseases, and osteoarthritis.

Potential negative side effects of long-term corticosteroid use include premature atherosclerosis, skin thinning/atrophy, adverse gastrointestinal effects, cataracts, depression, and sleep disturbances.

Birth control

As long as the patient is healthy and without contraindications such as nicotine use and thrombophilia, the long-term use of birth control—both estrogen-progestin and progestin-only formulations—is relatively safe, according to expert input from the Mayo Clinic. But studies have demonstrated that continued use is linked to certain cancers.

Based on the research, the Mayo Clinic suggested that “long-term use of estrogen-containing birth control pills is associated with an increased risk of cervical cancer. This risk increases the longer you take the pills. But once you stop taking the pills, the risk of cervical cancer begins to decline. Approximately 10 years after stopping birth control pills, cervical cancer risk returns to the same level as for women who have never taken birth control pills.”

The risk of estrogen-containing birth control pills on breast cancer isn’t as clear. “Some research indicates that taking estrogen-containing birth control pills slightly increases the risk of breast cancer—but that 10 or more years after stopping the pills, breast cancer risk returns to the same level as for women who have never taken birth control pills. Other studies don't support a link between estrogen-containing birth control pills and breast cancer,” according to the Mayo Clinic. 

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