The use of repurposed drugs, including hydroxychloroquine and ivermectin, increased significantly throughout the first two years of the coronavirus disease 2019 (COVID-19) pandemic. Hydroxychloroquine prescriptions rose by 65 to 80% in early 2020, whereas ivermectin usage surged later, with U.S. pharmacy sales rising approximately 1,000% in December 2020. Despite evidence of ineffectiveness and safety concerns, the use of these medications continued. This trend is influenced by various factors, such as misinformation, demographic differences, and mistrust in the healthcare system.
The recent retrospective cohort study published in Health Affairs aimed to examine the national trends in hydroxychloroquine and ivermectin use and spending during the COVID-19 public health emergency (January 2020 to May 2023) compared to the pre-pandemic period in U.S. outpatients. This study also assessed demographic variations and hypothesized continuous drug use among southern U.S. residents, vulnerable groups, and older adult populations.
This study used insurance claims data from the Milliman MedInsight Emerging Experience Research database, which covers 8.1 million patients (mean age = 51.1±19.5 years, 44.7% male, 55.1% female, 91.6% urban area, 25.3% West region) across 50 U.S. states. Different outcomes like overall and monthly utilization rates of study drugs (prescriptions per 1,000 patients) as well as aggregated total allowed amounts from prescription claims (spending) were analyzed. All statistical analysis was performed using a statistical package for the social sciences (SPSS) version 28.
The utilization rate of COVID-19-associated study drugs was 2.9 times higher in older adults (3.9 [95% confidence interval (CI): 3.3,4.3]) compared to younger populations (1.3 [95% CI: 1.0, 1.5]) with p < 0.001.
Hydroxychloroquine utilization rate was significantly lower in the most vulnerable group (expected rate = 99%) than in the least vulnerable group (expected rates = 119%) with p value of <0.001 during the public health emergency. While ivermectin was used at significantly higher rates among the most vulnerable population (expected rate = 223%) compared to the least vulnerable group (expected rates = 179%) with p < 0.0001 in the public health emergency.
During public health emergencies, the outpatient utilization rates of hydroxychloroquine did not significantly differ among U.S. census regions, with rates of 109% in the Northeast, 100% in the Midwest, 115% in the South, and 104% in the West of expected levels (p = 0.39). However, outpatient utilization rates of ivermectin were significantly higher in the South region (expected rates = 366%) compared to other three regions like West (expected rates = 200%), Midwest (expected rates = 178%) and Northeast (expected rates = 98%) with p < 0.0001. It was observed that usage of ivermectin drug was 3 to 4 times higher in the South region compared to all other regions in January 2021, August 2021 and January 2022.
Almost 3 million prescriptions were filled, resulting in $272 million in spending during this study period. Notably, 7% of these prescriptions occurred after the Food and Drug Administration (FDA) authorized outpatient COVID-19 drugs, including ritonavir-boosted molnupiravir, remdesivir, and nirmatrelvir. From January 2022 to June 2023, the availability of FDA-COVID-19 medicinal products courses per 100,000 U.S. residents was greater in the Northeast with 65,271 courses compared to the remaining three regions such as 46,033 in the South, 46,708 in the Midwest, and 47,542 in the West (p < 0.001).
This study’s limitations include results that may not fully generalize to the broader population, medications without insurance and prescriptions were not included, price variations among all U.S. pharmacies affect the spending estimates, and claims data do not specify the COVID-19 diagnosis. Finally, this study does not directly assess the causal factors influencing utilization rates of studied drugs.
This study concluded that the overall utilization rate of hydroxychloroquine and ivermectin was three times higher in older adults compared to younger adults. The usage of ivermectin was higher among the most vulnerable patients and in southern U.S. populations. These results can support policy efforts to minimize the harm of non-evidence-based treatment among vulnerable patients.
Reference: Rockwell MS, Vangala S, Hadfield M, et al. Demographic Variation In U.S. Outpatient Hydroxychloroquine And Ivermectin Use During TheCOVID-19 Pandemic. Health Aff. 2025;44(3):1-10. doi:10.1377/hlthaff.2024.00452
