CDC Opioid Guidelines Linked to Negative Consequences in Sickle Cell Disease

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The 2016 CDC guidelines led to significant decreases in opioid prescriptions and an increase in pain-related healthcare utilization for people with sickle cell disease.

Release of the 2016 Centers for Disease Control and Prevention (CDC) Guidelines for Opioid Prescription for Chronic Pain may have had unintended negative consequences for patients with sickle cell disease (SCD).1

Although the 2016 CDC guidelines were intended to promote safer and more effective use of prescription opioids in populations outside of SCD, both clinicians and patients have recognized its publication limited pain treatment in SCD.2

In particular, the identified negative outcomes for the population with SCD involved a decrease in opioid prescriptions and an increase in pain-related healthcare utilization.1

“Decreases in prescription opioids among those with SCD imply that this population was susceptible to the guideline’s recommendations and subsequent changes in regulations by state legislatures and health insurance organizations,” wrote the investigative team, led by Hyeun Ah Kang, PhD, The University of Texas at Austin.

Specific SCD guidelines recommend opioid analgesics if pain cannot be relieved by nonopioids—despite pain management needs, patients may face opioid-related restrictions. This is noted, in part, because SCD predominantly affects African-American individuals (90%), a group less likely than White counterparts to receive opioid prescriptions in the United States.3

By February 2019, the CDC acknowledged the 2016 guidelines did not intend to prevent individuals with acute or chronic pain from conditions, including cancer and SCD, from clinically necessary opioid treatment.4 Until its update in November 2022, no study had examined the guideline’s effect on individuals with SCD.5

As the updated guideline listed SCD as an excluded condition, owing to expert panel discussions and research identifying inadequate pain management among African-American patients, Kang and colleagues noted an evaluation of the 2016 guideline is necessary to prevent further unintended negative consequences for the population with SCD.1

For this study, an interrupted time series analysis was conducted on claims data from the Merative MarketScan Commercial Database, involving more than 25 million individuals, from January 2011 to December 2019. Based on a pre-identified algorithm, investigators identified individuals with SCD who were ≥1 year of age, had no cancer diagnosis, and had pharmacy coverage for the month of measurement.

Data analysis occurred between January 2021 and November 2023. Study outcomes related to opioid prescribing in SCD included the monthly rate of opioid prescription dispenses, mean number of days supplied, mean total morphine milligram equivalents (MME) per patient, and mean daily MME per opioid prescription. Pain-related outcomes included the rate of vaso-occlusive crisis (VOC)-related emergency department visits and monthly rates of VOC-related hospitalizations.

The study cohort included 14,979 patients with SCD, with a mean age of 25.9 years, consisting of 8520 (56.9%) female patients. In the pre-guideline period, the rate of opioid prescriptions in SCD was 0.81, which significantly declined after the guideline was released in March 2016 (–0.29 [95% CI, –0.39 to –0.20] prescriptions per 100 person-month; P <.001).

Compared with the pre-guideline period, other trends revealed significant decreases in the mean days supplied per opioid prescription (–0.05 [95% CI, –0.06 to –0.04]; P <.001) and opioid dosage per patient (–141.0 [95% CI, –0.06 to –0.04]; P <.001) and opioid prescription (–10.1 [95% CI, –14.6 to –5.6]; P <.001). On the other hand, the release of the guidelines correlated with a significant increase in VOC-related hospitalizations (0.16 [95% CI, 0.07 - 0.25) hospitalizations per 100 person-month; P = .001).

Analyses also demonstrated age-related changes in opioid prescription fills for patients with SCD. Compared with adults with SCD, pediatric patients received fewer opioid prescription fills, with lower dosages, and had fewer VOC-related visits during the study period.

Based on these findings, Kang and colleagues noted the CDC’s non-inclusion of SCD as an excluded condition in the guidelines, as well as the lack of guidance on disease-specific guidelines, may have reduced access to opioids and led to poor pain control in this population.

“The federal guideline and policymakers should carefully consider the negative outcomes that their interventions may present in vulnerable populations, as well as clearly communicate the intention and scope of the intervention,” investigators wrote.


  1. Kang HA, Wang B, Barner JC, et al. Opioid Prescribing and Outcomes in Patients With Sickle Cell Disease Post–2016 CDC Guideline. JAMA Intern Med. Published online March 11, 2024. doi:10.1001/jamainternmed.2023.8538
  2. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016 [published correction appears in MMWR Recomm Rep. 2016;65(11):295]. MMWR Recomm Rep. 2016;65(1):1-49. Published 2016 Mar 18. doi:10.15585/mmwr.rr6501e1
  3. Brousseau DC, Panepinto JA, Nimmer M, Hoffmann RG. The number of people with sickle-cell disease in the United States: national and state estimates. Am J Hematol. 2010;85(1):77-78. doi:10.1002/ajh.21570
  4. Centers for Disease Control and Prevention. CDC opioid guideline clarification letter. February 28, 2019. Accessed March 12, 2024.
  5. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95. Published 2022 Nov 4. doi:10.15585/mmwr.rr7103a1