糖心vlog

Racial and ethnic inequities in the receipt of medications to treat opioid use disorder (MOUD) have been well described. Ross and colleagues¹ provide an important addition to the existing literature on MOUD disparities, identifying racial differences in buprenorphine and methadone dosing across 3 trials completed within the National Institute on Drug Abuse Clinical Trials Network (CTN). Similar to prior research, Ross and colleagues¹ found a significant difference among methadone dosing among Non-Hispanic Black compared with Non-Hispanic White participants in their fully adjusted models.² Additionally, Ross and colleagues¹ describes differences in mean buprenorphine dosing and the proportion of participants receiving high buprenorphine or methadone doses among Non-Hispanic Black compared with Non-Hispanic White participants. Dosing disparities are particularly concerning because higher MOUD doses have been associated with greater retention in treatment.³ While the differences identified were not significant after covariate adjustment (sex, age, withdrawal symptom severity, comorbid conditions, and drug use history), overadjustment and small sample sizes, particularly for the Non-Hispanic Black and Hispanic participants, may have limited the findings.

The findings of Ross et al¹ must be understood in the context of the national randomized clinical trials whose data they analyzed. The first trial, the START trial (2006-2010), compared buprenorphine-naloxone and methadone in patients with opioid use disorder (OUD) with a primary outcome of liver function at 6 months (CTN-0027). Of note, a larger percentage of White participants who gave consent were randomized compared with individuals of other races and ethnicities (75% vs 64%).⁴ The second trial (2006-2009), the POATS study (CTN-0030 Phase 2), evaluated various doses of buprenorphine-naloxone with and without counseling for individuals with prescription opioid dependence, with a primary outcome of abstinence from nonprescribed opioids. Of note, this trial had the lowest rate of Non-Hispanic Black and Hispanic participants (7.5% compared with 27% in CTN-0027 and 30% in CTN-0051). Finally, the third trial, the X:BOT study (2014-2016), compared the effectiveness of intramuscular naltrexone vs buprenorphine-naloxone (CTN-0051). The first 2 trials took place prior to the introduction of fentanyl in the drug supply, with its emergence overlapping with CTN-0051. The Ross et al¹ secondary analysis pooled heterogeneous data on buprenorphine and methadone dosing and evaluated differences by race and ethnicity during the first 4 weeks of treatment. All studies included randomized treatment assignment and participants were from sites across the country. Each trial protocol provided similar dosing recommendations and allowed clinicians the flexibility to make adjustments based on clinical or subjective opioid withdrawal scores and clinical judgment.

For a patient initiating methadone or burprenorphine to stabilize, a number of steps are necessary. First, they need to be assessed for, and diagnosed with, OUD. Then, they need access to a clinician who can prescribe MOUD or admission to an opioid treatment program, both of which require overcoming stigma, insurance, and transportation-related barriers. If the patient receives buprenorphine, certain insurance plans require prior authorizations for higher doses, mandate behavioral treatment attendance, or require frequent urine drug testing.⁵ These barriers can be factors in stigma against addiction and may require additional clinical resources, which limits timely access to medications. For individuals receiving methadone, they typically must attend a specialized clinic daily and receive their medications under supervision. These clinics are only available in certain geographic areas and are often concentrated in high-poverty neighborhoods. Once a medication has been initiated, identifying stabilization with the right dose often requires frequent dose adjustments over several weeks. Finally, individuals must continue to take the medication as prescribed, attend follow-up visits, and meet treatment program requirements. Each step is subject to individual biases from clinicians, stigma against addiction, and structural racism in and outside of the health care setting鈥揾indering progression along the OUD cascade of care. Policies within health care organizations, as well as state and national restrictive opioid-related policies, have had a negative impact in patient access to care and retention in care, especially for Black patients.

While the clinical trial setting removes many barriers to medication access early in this pathway once enrolled, disparities in trial enrollment by race can affect the generalizability of the findings and limit confidence in the effectiveness of new treatments in clinical settings when participants are disproportionately Non-Hispanic White, as was particularly the case in CTN-0030.⁶ The Ross and colleagues¹ assessment of dosing disparities in a clinical trial setting hones in on the penultimate step in the OUD cascade of care, as individuals transition from nonprescribed use to stabilization in use of MOUD through dose adjustments in the first month of treatment. Notably, Ross and colleagues¹ identified that the opioid withdrawal scores were lower for Black Non-Hispanic participants compared with White participants in both the buprenorphine and methadone groups, similar to an earlier trial within the CTN network.⁶ The reasons for this difference are not clear, but given that the study protocols encouraged clinicians to guide dosing decisions based on these scores, we hypothesize that withdrawal scores may be an important mediator of the identified association between race and ethnicity and MOUD dose. Adjusting for the withdrawal scale scores as confounders in the full model, as Ross et al¹ have done, has the potential to underestimate the true association between race and dosage.

Factors that may affect withdrawal scores include type of opioid (fentanyl or heroin), route of administration (intravenous vs intranasal), biases in clinician assessments, and differences in clinical presentation. Notably, when stratified by withdrawal severity, the dosing differences between Black participants and White participants were greatest in the mild/none severity cohort compared with the moderate/severe group. Black participants may feel pressured to minimize behavioral signs of withdrawal such as irritability, anxiety, and restlessness, due to prior experiences of discrimination in health care settings. Black patients with OUD report a lack of empathy and respect from clinicians when seeking care.⁷ Studies have shown that Black people adjust their appearance and behavior, including being less assertive, when seeking health care to avoid being perceived as aggressive.⁸ Future analyses could examine whether disparities exist in more subjective symptoms compared with objective signs (eg, heart rate, pupil size) in the withdrawal scales.

Outside of the clinical trial setting, barriers to higher doses of buprenorphine persist, and may disproportionately affect Black and Hispanic individuals with OUD. Certain insurance plans may impose dosing limits or require justification for doses beyond 16 mg.⁵ Longer-acting injectable formulations of buprenorphine confer substantially higher plasma concentrations than sublingual formulations; however, lack of insurance coverage can be a barrier. Additionally, administration of injectable formulations requires visits with an addiction specialist who has the medication stocked, which has been less accessible in neighborhoods where Black, Hispanic, and low-income individuals reside.

Racial disparities at each step of the OUD cascade of care are at the root of ongoing inequities in overdose morbidity and mortality. The findings by Ross and colleagues,¹ specifically that reported withdrawal severity may be factors associated with the unadjusted disparities in buprenorphine and methadone dosing, suggest the possibility of an underexplored pathway through which disparities arise: potential differences in severity grading due to the subjective nature of clinician observations of certain opioid withdrawal symptoms. Underreporting or underappreciation of withdrawal symptoms and reported cravings due to structural and historical factors that shape interpersonal dynamics during clinical encounters may explain downstream disparities in retention in treatment and adverse opioid outcomes, and call for evaluation of more objective diagnostic tools that are critical for therapeutic accuracy.

Open Access: This is an open access article distributed under the terms of the CC-BY License. 漏 2024 Schiff DM et al. 糖心vlog Open.

Published: October 4, 2024. doi:10.1001/jamanetworkopen.2024.36582

Correction: This commentary was corrected on November 1, 2024, to fix an error in the second paragraph.

Corresponding Author: Davida M. Schiff, MD, MSc, Division of General Academic Pediatrics, MassGeneral Hospital for Children, 125 Nashua St, Ste 860, Boston, MA 02114 (davida.schiff@mgh.harvard.edu).

Conflict of Interest Disclosures: None reported.