These are America’s top-prescribed medications

By Naveed Saleh, MD, MS
Published May 5, 2021

Key Takeaways

It’s tempting to think that there isn’t much to learn about the most frequently prescribed medications in the United States. After all, their indications and potential adverse effects must be pretty well-appreciated for so many physicians to rely on them. But, even with the most popular drugs, intriguing research emerges with each passing year.

DrugReport is a site that informs consumers about the risks and dangers of prescription drugs and medical devices. This site keeps close tabs on consumer-related data, including which drugs are prescribed most. 

“We are a team of journalists passionate about uncovering the truth about prescription drugs and medical devices that can cause harm,” according to the site. “We report on injuries and deaths they have caused, as well as legal action that has followed. Our mission is to inform consumers of this harm, as a way to safeguard them from it.”

The site most recently published a list of the most prescribed drugs in the United States in a 2020 article. Of note, year-end tabulations of prescription numbers are often dated, and no year-to-date tally for 2021 exists yet. Nevertheless, from the lists we’ve surveyed, the most popular prescription drugs largely overlap from year to year. Let’s look at the top five according to DrugReport, along with new research on these agents. (Number of annual prescriptions rounded.)

1. Lisinopril (Qbrelis, Prinivil, Zestril)

Number of annual prescriptions: 105 million

Average price-per-prescription: $27.10

The ACE inhibitor lisinopril is used to treat high blood pressure and prevent heart failure. More common adverse effects of this drug include dizziness, headache, low blood pressure, and fatigue.

Various recent case reports, however, have highlighted a curious adverse effect of the drug: psoriasis. In a recent study published in Pharmazie, researchers mined FDA Adverse Event Reporting System (FAERS) data to determine the association between psoriasis and 14 ACE inhibitors. Researchers excluded patients with psoriasis-related primary diseases. They determined the reporting odds ratio for the 14 ACE inhibitors combined was 1.25 and that for lisinopril alone, it was 1.20.

“ACE inhibitors are widely used in patients with hypertension, heart failure, and diabetes mellitus, which are considered comorbidities of psoriasis,” they wrote. “Our results suggest that the involvement of ACE inhibitors should be considered in patients on ACE inhibitor therapy who have developed (or show exacerbated) psoriasis.”

2. Atorvastatin (Lipitor)

Number of annual prescriptions: 105 million

Average price-per-prescription: $218.51

Atorvastatin is used to treat high LDL levels and decrease the risk of heart attack and stroke. Patients with poorly controlled cardiovascular disease often also have type 2 diabetes, as these conditions are intertwined. In those with diabetes, however, the efficacy of statins such as atorvastatin can drop, according to the results of a review published in BioMed Research International.

The authors’ findings showed that “diabetes affected statin effectiveness through changes in pharmacokinetic parameters such as clearance and biotransformation biomarkers at mRNA and protein levels. Plasma and serum concentrations of statins were accompanied by alteration in cellular activities including oxidative stress, Akt inhibition, and endothelial nitric oxide synthase (eNOS) and phosphorylation that were reflected in changes in the adverse drug reaction profile of the differing statins. Given that dyslipidemia frequently accompanies diabetes and statin therapy is common, more clinical studies are needed regarding the effects of diabetes on the effectiveness of these drugs.”

3. Levothyroxine (Levothroid, Levoxyl, Tirosint)

Number of annual prescriptions: 102 million

Average price-per-prescription: $31.29

Levothyroxine is used to treat hypothyroidism. Intriguingly, another treatment for hypothyroidism may be bariatric surgery.

According to the results of a meta-analysis and systematic review published in Surgery for Obesity and Related Diseases, the authors found that subclinical hypothyroidism was completely resolved in 87% of patients receiving bariatric surgery. In frank hyperthyroid patients, they noted a significant decrease in levothyroxine doses required. These results spanned Roux-en-Y gastric bypass, one anastomosis gastric bypass, and sleeve gastrectomy.

4. Metformin (Fortamet, Glumetza, Glucophage)

Number of annual prescriptions: 79 million

Average price-per-prescription: $16.25

Metformin is a first-line medication that is a mainstay for diabetes treatment. The long-term effects of continuous metformin use, however, need to be elucidated.

According to the results of a retrospective study involving a cohort of 22,638 individuals from Hong Kong, metformin may protect against pneumonia. During a mean follow-up period of 7.5 years, the investigators found that after discounting other covariates including use of other glucose-lowering drugs (GLDs), the HR for first pneumonia hospitalization was 0.63 (95% CI 0.52, 0.77) and that for pneumonia-related death was 0.49 in metformin users compared with users of other GLDs.

“Long-term use of metformin was associated with reduced risk of pneumonia and pneumonia-related death among Chinese individuals with diabetes,” they concluded. “The relevance of these results to other respiratory infections merits further investigation.”

5. Amlodipine (Amvaz, Katerzia, Norvasc)

Number of annual prescriptions: 73 million

Average price-per-prescription: $27.34

The calcium-channel blocker amlodipine is used to treat high blood pressure, coronary artery disease, and chest pain. Surprisingly, it may also harbor antiviral effects.

Recent studies have suggested that calcium-channel blockers (CCBs) such as amlodipine and nifedipine can decrease mortality caused by COVID-19. Hypocalcemia has been demonstrated to be linked with COVID-19 severity, and the efficacy of CCBs as antiviral therapy, as well as positive relationships with hypocalcemia and mortality, have been demonstrated with other viruses as well. 

According to the authors of a review article published in Evolution, Medicine, and Public Health, “Considerable evidence supports the hypothesis that hypocalcemia represents a host defence. Indeed, hypocalcemia may exert antiviral effects in a similar manner as do CCBs, through interference with calcium metabolism in virus-infected cells. Prospective clinical studies that address the efficacy of CCBs and hypocalcemia should provide novel insights into the pathogenicity and treatment of COVID-19 and other viruses.”

MDLinx previously reported on a number of medications that are considered “overprescribed.” Read about those drugs here

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