Intersectional Risk and the Significant Gap in Care for Persons with Co-occurring Chronic Pain and Opioid Withdrawal.

OBJECTIVES: Persons with chronic pain and women tend to enter treatment for opioid use disorder with greater opioid withdrawal severity than persons without chronic pain and men, respectively. This study examined characteristics of facilities with opioid withdrawal treatment, including gender-based services, as a function of whether they reported having a tailored pain management program. METHODS: The National Survey of Substance Abuse Treatment Services 2020 was used to examine 3942 facilities with opioid withdrawal treatment in the United States. Using a multivariable binary logistic regression model, facilities were examined for the presence of a tailored program for individuals with co-occurring pain. Regional location of the facility, ownership status, and availability of tailored gender programs, nonhospital residential services, and outpatient services served as independent variables in the analysis. RESULTS: A slight majority of the sample had a program for both adult men and adult women (n = 2010, 51.0%). Most facilities had outpatient services (n = 3289, 83.4%) and did not have a tailored program for addressing co-occurring pain (n = 2756, 69.9%). Binary logistic regression analysis showed that among opioid withdrawal facilities, programs with nonhospital residential services, government or private nonprofit funding, or tailored gender programming had higher odds of reporting having a tailored program for pain and substance use disorder. Facilities in the Western United States were most likely to have tailored programs for pain and substance use disorder. CONCLUSIONS: Future research should investigate what support patients may receive and how to better scale access to pain management during opioid withdrawal treatment.

Fentanyl Absorption, Distribution, Metabolism, and Excretion: Narrative Review and Clinical Significance Related to Illicitly Manufactured Fentanyl.

OBJECTIVES: This narrative review summarizes literature on pharmaceutical fentanyl's absorption, distribution, metabolism, and excretion patterns to inform research on illicitly manufactured fentanyl (IMF). RESULTS: Fentanyl is highly lipophilic, lending itself to rapid absorption by highly perfused tissues (including the brain) before redistributing from these tissues to muscle and fat. Fentanyl is eliminated primarily by metabolism and urinary excretion of metabolites (norfentanyl and other minor metabolites). Fentanyl has a long terminal elimination, with a documented secondary peaking phenomenon that can manifest as "fentanyl rebound." Clinical implications in overdose (respiratory depression, muscle rigidity, and "wooden chest syndrome") and opioid use disorder treatment (subjective effects, withdrawal, and buprenorphine-precipitated withdrawal) are discussed. The authors highlight research gaps derived from differences in medicinal fentanyl studies and IMF use patterns, including that medicinal fentanyl studies are largely conducted with persons who were opioid-naive, anesthetized, or had severe chronic pain and that IMF use is characterized by supratherapeutic doses and frequent and sustained administration patterns, as well as adulteration with other substances and/or fentanyl analogs. CONCLUSIONS: This review reexamines information yielded from decades of medicinal fentanyl research and applies elements of the pharmacokinetic profile to persons with IMF exposure. In persons who use drugs, peripheral accumulation of fentanyl may be leading to prolonged exposure. More focused research on the pharmacology of fentanyl in persons using IMF is warranted.

Operational definition of precipitated opioid withdrawal.

Background: Opioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal. Methods: People (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA). Results: Within 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1-40, 41-80, and 81-100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal. Conclusion: Data suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal.