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CDC Guideline Results in Drop in Opioid Prescriptions for Patients with Sickle Cell Disease

May 24, 2024

June 2024

Anna Azvolinsky, PhD

Anna Azvolinsky, PhD, is a freelance medical and science journalist based in New York City.

In 2016, the U.S. Centers for Disease Control and Prevention (CDC) released the Guideline for Prescribing Opioids for Chronic Pain to provide recommendations to primary care clinicians who prescribe opioids for chronic pain to adults outside of active cancer treatment, palliative care, and end- of- life care. The guidelines were subsequently amended to exclude people with sickle cell disease (SCD).

Now, researchers have examined whether the guideline has affected prescribing patterns of pain medications and the health outcomes for patients with SCD. The study found a significant increase in hospitalizations related to vaso-occlusive crises (VOC) among patients with SCD in the U.S. after the release of the opioid guideline. The findings, published in JAMA Internal Health, suggest that the guideline may have resulted in unintended negative consequences for pain management among those with SCD.

“Our study was motivated by concerns regarding the unintended consequences of the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain on patients with SCD,” said author Hyeun Ah Kang, PhD, an assistant professor of health outcomes at the University of Texas at Austin College of Pharmacy. “Despite the guideline’s intention to promote safer opioid use for chronic pain, there were worries among clinicians that it might inadvertently limit access to necessary pain management for populations, including for those with SCD.”

Dr. Kang and her colleagues used claims data from the Merative MarketScan Commercial Database from January 2011 to December 2019 to analyze the rate of opioid prescriptions dispensed, as well as the average number of days supplied, the total morphine milligram equivalents (MME) per patient, and daily MME per opioid prescription. They also tracked pain-related health outcomes such as rates of emergency department visits and hospitalizations related to VOC.

The study included 14,979 patients with SCD who were at least 1 year of age, had no cancer diagnosis, and had pharmacy coverage. The mean age of patients was 25.9 years, and a higher proportion (56.9%) of participants was female.

The researchers found that, after the release of the CDC guideline in March 2016, there was a significant decrease in the rate of opioid prescriptions dispensed to patients with SCD. This decline continued through December 2019, resulting in a substantial reduction in opioid prescription fills compared to the pre-guideline period by 0.29 prescriptions per 100 person-month (p<0.001). The number of days supplied per prescription also decreased by 0.05 days per prescription-month (p<0.001), and the opioid dosage decreased by 141 mean total MME per person-month (p=0.001).

“These results suggest that patients with SCD were receiving fewer opioid prescriptions, a lower dosage per prescription, and shorter durations post-guideline implementation,” Dr. Kang said.

In parallel to these trends, the data showed an increase in VOC-related hospitalizations among patients with SCD (by 0.16 hospitalizations per 100 person-month; p=0.001).

Although both adult and pediatric patients experienced decreases in opioid prescriptions and increases in pain-related hospitalizations, these changes were mostly greater for adult patients.

The authors also found a substantial increase in daily MME per opioid prescription a few months before and after the guideline publication. “This unique trend has not been observed in previous studies with other populations. Although the reason for this increase is uncertain, one potential reason is that prescribers may have been encouraged to ensure patient access to opioids around the time the guideline became available for public comments, which was December 2015, assuming they anticipated their own institutions, health plans, or states would implement more restrictive policies per the CDC guideline,” Dr. Kang said.

Limitations of the study include a lack of a control group that was not exposed to the CDC guideline, an inability to distinguish between opioid prescriptions for acute versus chronic pain among patients with SCD, and the use of claims data for the analyses.

The authors are planning a follow-up study using the same data set that will compare opioid prescribing trends for patients with SCD before and after the CDC guideline between specialized providers such as hematologists versus primary care providers and emergency room physicians.

Any conflicts of interest declared by the authors can be found in the original article.


Kang HA, Wang B, Barner JC, et al. Opioid prescribing and outcomes in patients with sickle cell disease post–2016 CDC guideline [published online ahead of print, 2024 March 11]. JAMA Intern Med. doi: 10.1001/jamainternmed.2023.8538.


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