The association of pain impact and sleep disruption with opioid withdrawal during opioid-use disorder treatment.

AIMS: Persons with opioid-use disorder (OUD) often experience opioid withdrawal and opioid craving, which can drive continued opioid use and treatment discontinuation. In addition, hyperalgesia is common among persons with OUD, yet few studies have examined the role of pain impact during OUD treatment. The purpose of the present study was to test whether opioid withdrawal and craving were elevated in the context of greater pain impact (i.e. greater pain intensity and interference), and whether these associations changed throughout treatment. METHODS: Participants in residential OUD treatment (n = 24) wore wrist actigraphy to measure sleep and completed daily measures of pain impact, opioid withdrawal and opioid craving for up to 28 days. Mixed effects models were used to examine whether daily elevations in pain impact and sleep continuity were associated with withdrawal severity and opioid craving. RESULTS: Elevations in withdrawal, but not craving, occurred on days when individuals reported higher scores on the pain impact scale. Associations between pain impact and withdrawal were present throughout treatment, but stronger during early treatment. In contrast, both withdrawal and opioid craving were elevated following nights of greater wake after sleep onset and awakenings, but these findings were often more pronounced in early treatment. CONCLUSIONS: Pain impact and sleep disturbance are 2 factors associated with opioid withdrawal and opioid craving. Novel pharmacotherapies and scalable adjunctive interventions targeting sleep and pain impact should be tested in future work to improve OUD treatment outcomes.

Age moderates the association of optimism on craving during substance use disorder treatment.

BACKGROUND: Optimism, characterized by a positive expectancy toward future outcomes, has garnered attention for its potential role in influencing well-being and may be a protective factor in substance use disorder (SUD) treatment. This study evaluated the relationship of optimism and craving among those in substance use disorder SUD treatment. METHODS: Drawing from a cohort of 4201 individuals in residential SUD treatment programs, this study used both cross-sectional and longitudinal assessment to examine tonic (steady-state) and cue-induced (phasic) cravings across individuals primarily using eight classes of substances. Previous research established that optimism increases during adulthood and peaks during an individual's 50s. This study sought to establish if the association between optimism and craving is moderated by age during the first week of treatment and if that relationship changes over the course of treatment both within and between-person. RESULTS: This study found a negative correlation between optimism and craving intensity. Elevated optimism scores correlated with substantially reduced levels of both tonic (ß = -0.31, p < 0.001) and cue-induced (ß = -0.29, p < 0.001) cravings. Age was a significant moderator of the relationship between optimism and craving such that as individuals age, the potency of optimism in mitigating cravings gradually attenuates (interaction for tonic craving: ß = 0.06, p < 0.001; interaction for cue-induced craving: ß = 0.05, p < 0.001). Reflected in the fact that in older individuals' cravings tended to converge toward lower or moderate levels, regardless of their optimism scores. CONCLUSIONS: By delineating the contemporaneous association between high optimism and lower cravings, the study suggests that interventions aimed at fostering optimism may represent an avenue to improve the effectiveness of SUD treatment, especially in emerging adults.

A brief measure of non-drug reinforcement: Association with treatment outcomes during initial substance use recovery.

BACKGROUND: Translational research demonstrates that drug use is inversely associated with availability and engagement with meaningful non-drug reinforcers. Evaluation of non-drug reinforcement in treatment-receiving clinical populations is limited, likely owing to the time intensive nature of existing measures. This study explores the association of non-drug reinforcers with treatment outcomes using a novel, brief measure of past month non-drug reinforcement quantifying three elements: relative frequency, access, and enjoyability. METHODS: Respondents enrolled in substance use treatment (residential, intensive outpatient, and medically managed withdrawal) in clinics across the United States (N = 5481) completed standardized assessments of non-drug reinforcement and treatment outcomes (i.e., return to use and life satisfaction) one-month after treatment discharge. Non-drug reinforcement measures (availability, engagement, enjoyability) were used as predictors of return to use and life satisfaction using generalized linear models. RESULTS: Non-drug reinforcement indices were associated with return to use and life satisfaction in unadjusted models (e.g., 12.4 % versus 58.3 % return to use for those with the highest and lowest availability, respectively). Consistent results were observed in models adjusted for sociodemographic variables and risk factors (i.e., sleep disturbance, anhedonia, stress). Comparisons by drug class generally showed lower non-drug reinforcement among patients reporting heroin or methamphetamine as their primary drug. CONCLUSIONS: Results highlight the importance of non-drug reinforcement during the first month following treatment. Rapid measurement of non-drug reinforcement in stepped care settings may illuminate critical deficits in early stages of behavior change, identify those at greatest risk for return to use, and provide targets for treatment to improve recovery trajectories.

The impact of opioid-stimulant co-use on tonic and cue-induced craving.

The twin opioid-stimulant epidemics have led to increased overdose deaths and present unique challenges for individuals entering treatment with opioid-stimulant polysubstance use. This study examined tonic and cue-induced craving as a primary outcome among persons in substance use treatment who reported primary substances of opioids, methamphetamine, or cocaine. The sample consisted of 1974 individuals in 55 residential substance-use treatment centers in the United States in 2021. Weekly surveys were delivered via a third-party outcomes tracking system, including measures of tonic and cue-induced craving. Initial comparisons on tonic and cue-induced craving were made among those who primarily used opioids, cocaine, or methamphetamine. Further, the effect of opioid/stimulant polysubstance use on tonic and cue-induced craving was evaluated using marginal effect regression models. Primary methamphetamine use was associated with decreased tonic craving compared to primary opioid use (ß = -5.63, p < 0.001) and primary cocaine use was also associate with decreased tonic craving compared to primary opioid use (ß = -6.14, p < 0.001). Primary cocaine use was also associated with lower cue-induced cravings compared to primary opioid use (ß = -0.53, p = 0.037). Opioid-methamphetamine polysubstance use was associated with higher tonic craving (ß = 3.81, p = <0.001) and higher cue-induced craving (ß = 1.55, p = 0.001); however, this was not the case for opioid-cocaine polysubstance use. The results of this study indicate that individuals who primarily use opioids and have secondary methamphetamine use experience higher cue-induced and tonic-induced craving, suggesting that these individuals may benefit from additional interventions that target craving and mitigate relapse risk and other negative sequelae.

Latent patterns of sleep disturbance, pain impact, and depressive symptoms in residential substance use treatment.

AIM: Sleep disturbance, clinically significant pain, and depressive symptoms commonly occur together among individuals with substance use disorders. The purposes of the present study were to 1) identify subgroups of individuals with heterogenous patterns of pain, sleep disturbance, and depressive symptoms, and 2) identify demographic and clinical correlates of profile membership. MATERIAL AND METHODS: The present study assessed a sample (N = 8621) of individuals seeking residential substance use treatment in 2020 and 2021 in the United States. We examined whether unique sub-groups could be identified based on patterns of sleep disturbance, pain impact, and depressive symptoms during the first four weeks of treatment, using longitudinal latent profile analysis. Next, we explored demographic, substance use, and clinical correlates (i.e., distress intolerance) of profile membership, as well as whether profile membership was associated with treatment attrition. RESULTS: The identified classes were: 1) Low sleep disturbance, pain impact, and depressive symptoms, 2) High pain, remitting depressive symptoms, and mild sleep disturbance, 3) High depressive symptoms, low pain, and remitting sleep disturbance, and 4) High sleep disturbance, pain impact, and depressive symptoms. Individuals with high pain, depressive symptoms, and sleep disturbance were more likely to be older, use opioids as their primary substance, have high distress intolerance, and discontinue treatment. CONCLUSION: Results highlight the importance of comprehensive care and management of physical health conditions, particularly among older adults. Further, results highlight that distress intolerance may be a modifiable risk factor for co-occurring sleep disturbance, pain impact, and depressive symptoms.

A double-blind, randomized, placebo-controlled, pilot clinical trial examining buspirone as an adjunctive medication during buprenorphine-assisted supervised opioid withdrawal.

Successful management of opioid withdrawal improves long-term treatment outcomes and reduces opioid use-related morbidity and mortality. Mechanistically supported pharmacotherapeutic approaches are needed to effectively manage acute and protracted opioid withdrawal. Buspirone is a D2 antagonist and 5-HT1a agonist that may decrease opioid withdrawal. Individuals (n = 15) admitted to a residential treatment center for opioid use disorder (OUD) were enrolled into a double-blind randomized clinical trial to assess the efficacy and acceptability of buspirone (45 mg/day) as an adjunctive medication to buprenorphine-assisted, supervised opioid withdrawal. Participants completed daily questionnaires which consisted of the Subjective Opiate Withdrawal Scale (SOWS) and a consensus sleep diary, which assessed total sleep time, time to sleep onset, and sleep quality. Total SOWS scores, individual opioid withdrawal symptoms and sleep outcomes were assessed between treatment groups (Placebo and Buspirone) and over time in a repeated measures linear mixed model. Total SOWS scores significantly decreased across study phases for both groups but decreased to a greater extent among individuals assigned to buspirone during both the first and second week of stable buspirone. Greater decreases in withdrawal were observed during Week 2 of stable buspirone relative to Week 1 of stable buspirone. Participants also reported significant increases in sleep duration and significant decreases in latency to sleep onset. This study provides further support that buspirone can help mitigate opioid withdrawal during a supervised opioid taper. Buspirone may confer unique benefits during protracted withdrawal periods. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The association of chronic pain and opioid withdrawal in men and women with opioid use disorder.

BACKGROUND: Approximately 2.7 million individuals in the United States had an opioid use disorder (OUD) in 2020. Chronic pain may exacerbate opioid withdrawal severity, yet most research on opioid withdrawal has not collected data on chronic pain status. Moreover, there is limited evidence that women tend to experience greater opioid withdrawal severity than men, but large, confirmatory studies on this topic have not been published. The goal of this study was to examine the roles of chronic pain and gender on opioid withdrawal severity using a large, multi-site database. METHODS: Data were collected from N = 1252 individuals with OUD entering eight residential addiction treatment facilities. Demographic, drug use behaviors, and chronic pain status were collected at treatment intake, and self-reported opioid withdrawal and craving were measured at intake and 1-3 days, 4-6 days, and 7-9 days after intake. Regression analyses were used to predict withdrawal and craving severity at intake and across the four timepoints. RESULTS: At intake, withdrawal was higher in persons who were older, had greater SUD severity, women, had chronic pain, and used > 1 substance (p-values ≤.007) and craving was higher in persons with greater SUD severity (p < .001) and women (p = .033). Withdrawal remained higher in women and persons with chronic pain across timepoints but decreased at a similar rate relative to comparators. CONCLUSIONS: Women and persons with chronic pain would benefit from earlier engagement in treatment and may require a more intensive strategy to mitigate opioid withdrawal in early treatment.

Patient perceptions of higher-dose naloxone nasal spray for opioid overdose.

BACKGROUND: Higher-dose formulations of naloxone were recently approved by the FDA for the treatment of opioid overdose. These products were developed based on projected saturation of high-potency fentanyl analogues in the illicit marketplace although the evidence base for their necessity is still under scrutiny. Concern has been raised that unintended reductions in patient acceptance of naloxone may occur due to increased precipitated withdrawal risk associated with higher naloxone doses. A well-founded and time-sensitive call for representation of people who use drugs in this decision-making process has been made. This study provides the first data on patient perceptions of higher-dose formulations to inform this scientific debate and distribution efforts. METHODS: Patients (N=1152) entering treatment for opioid use disorder at one of 49 addiction treatment facilities located across the United States completed a preference assessment of naloxone nasal spray formulations. Patients selected a formulation preference across three scenarios (administration for self, administration to others, community responder administration). RESULTS: A majority of respondents that had been administered naloxone previously reported that their most recent overdose reversal included two or more naloxone administrations (59.9%). Most respondents either had no preference (48.4%) or preferred a higher-dose formulation (35.9%) if personally experiencing an overdose. Similar preference distributions were observed for administration to others and by community responders. Relative to standard-dose preference, respondents preferring higher-dose formulations had a greater odds of recent suspected fentanyl exposure. CONCLUSIONS: These data inform patients, advocates, and policy-makers considering distribution and utilization of naloxone formulations by reporting perspectives of patients with opioid use and overdose experience. Limited evidence for widespread avoidance of higher-dose formulations was found. As real-world evidence of acceptability and effectiveness emerges, either supporting or refuting the widespread need for higher-dose naloxone formulations, it is the responsibility of the scientific and public health community to be responsive to those data.

Integration of Patient-reported Outcomes Assessment Into Routine Care for Patients Receiving Residential Treatment for Alcohol and/or Substance Use Disorder.

BACKGROUND: More than 3 million individuals receive treatment for alcohol use disorder (AUD) and/or substance use disorder each year, yet there exists no standardized method for measuring patient success in treatment. Quantifying a more comprehensive assessment of treatment outcomes could identify the relative efficacy of different treatment strategies for individuals with AUD/substance use disorders, and help patients to identify, in advance, appropriate treatment options. METHODS: This study developed and embedded patient-reported outcome measures into the routine clinical operations of a residential treatment program. Surveys assessed demographics, drug use history, physical and mental health, and quality of life. Outcomes were assessed among participants at admission (n = 961) and in patients who completed the survey at time of discharge (n = 633). RESULTS: Past 30-day alcohol and/or opioid use at admission were correlated with worse self-reported physical and mental health, sleep, and quality of life, and greater negative affect and craving ( P s < 0.05). Previous history of treatment and/or withdrawal management were associated with worse self-reported physical and mental health, quality of life, and increased craving ( P s < 0.05). Physical and mental health improved across timepoints and was most pronounced when comparing persons receiving treatment for opioid use disorder versus AUD, wherein persons with opioid use disorder had worse physical health at all time points, and greater sleep disturbance and negative affect at discharge ( P s < 0.05). CONCLUSIONS: It is feasible to embed patient outcome monitoring into routine clinic operations, which could be used in the future to tailor treatment plans.

Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl.

OBJECTIVES: Buprenorphine can precipitate withdrawal in opioid-dependent persons with recent fentanyl use. However, the prevalence of this phenomenon is not clinically established. We sought to evaluate the incidence of buprenorphine-precipitated withdrawal in persons who use fentanyl. METHODS: We collected self-report data on opioid withdrawal symptoms after buprenorphine use, and, as a comparator, after methadone use, in 1679 individuals seeking treatment for opioid use disorder across 49 addiction treatment centers in the United States. RESULTS: The odds of developing severe withdrawal symptoms significantly increased when taking buprenorphine within 24 hours after fentanyl use (OR = 5.202, 95% CI = 1.979-13.675, P = 0.001), and within 24 to 48hours after fentanyl use (OR = 3.352, 95% CI =1.237-9.089, P = 0.017). As expected, patients did not report significantly higher rates of withdrawal when taking methadone after fentanyl use. Of those who waited less than 24hours after fentanyl before using buprenorphine or methadone, 22.19% (n = 152 of 685) and 11.56% (n = 23 of 199), respectively, reported severe opioid withdrawal. CONCLUSIONS: This study supports previous anecdotal reports of buprenorphine-precipitated withdrawal from fentanyl. The odds of withdrawal symptoms significantly increased when taking buprenorphine after recent (within 48 hours) fentanyl use, however, this relationship was not observed in persons taking methadone, suggesting that this effect is specific to buprenorphine. Further research is urgently needed to describe the pharmacokinetics of non-medical fentanyl use to improve buprenorphine inductions strategies.

Protracted renal clearance of fentanyl in persons with opioid use disorder.

INTRODUCTION: The illicit opioid supply in the U.S. is increasingly adulterated with fentanyl. As such, persons with opioid use disorder (OUD) may be regularly exposed to fentanyl, however, the pharmacokinetics of repeated fentanyl exposure are not well understood. The current study aimed to quantify renal clearance of fentanyl in OUD patients presenting to residential treatment. METHODS: Participants (N = 12) who presented to a 28-day residential treatment program were enrolled if they tested positive for fentanyl at intake. Urine samples were collected every 2-3 days and were quantitatively tested for fentanyl, norfentanyl, and creatinine via liquid chromatography mass spectrometry (LC-MS). Fentanyl clearance was defined as the time since last illicit opioid use and the median time between last positive and first negative fentanyl urine screen. RESULTS: Participants had a mean and standard deviation (SD) age of 28.9 (11.0), were 67 % male, and 83 % white. The mean (SD) time for fentanyl and norfentanyl clearance was 7.3 (4.9) and 13.3 (6.9) days, respectively. One participant continued to test positive for fentanyl for 19 days and norfentanyl for 26 days following their last use, and left treatment without testing negative for norfentanyl. CONCLUSION: Fentanyl clearance in persons with OUD is considerably longer than the typical 2-4 day clearance of other short-acting opioids. The findings of this study might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.

Differences in Availability and Use of Medications for Opioid Use Disorder in Residential Treatment Settings in the United States.

Importance: While many individuals with opioid use disorder seek treatment at residential facilities to initiate long-term recovery, the availability and use of medications for opioid use disorder (MOUDs) in these facilities is unclear. Objective: To examine differences in MOUD availability and use in residential facilities as a function of Medicaid policy, facility-level factors associated with MOUD availability, and admissions-level factors associated with MOUD use. Design, Setting, and Participants: This cross-sectional study used deidentified facility-level and admissions-level data from 2863 residential treatment facilities and 232 414 admissions in the United States in 2017. Facility-level data were extracted from the 2017 National Survey of Substance Abuse Treatment Services, and admissions-level data were extracted from the 2017 Treatment Episode Data Set-Admissions. Statistical analyses were conducted from June to November 2019. Exposures: Admissions for opioid use disorder at residential treatment facilities in the United States that identified opioids as the patient's primary drug of choice. Main Outcomes and Measures: Availability and use of 3 MOUDs (ie, extended-release naltrexone, buprenorphine, and methadone). Results: Of 232 414 admissions, 205 612 (88.5%) contained complete demographic data (166 213 [80.8%] aged 25-54 years; 136 854 [66.6%] men; 151 867 [73.9%] white). Among all admissions, MOUDs were used in only 34 058 of 192 336 (17.7%) in states that expanded Medicaid and 775 of 40 078 (1.9%) in states that did not expand Medicaid (P < .001). A relatively low percentage of the 2863 residential treatment facilities in this study offered extended-release naltrexone (854 [29.8%]), buprenorphine (953 [33.3%]), or methadone (60 [2.1%]). Compared with residential facilities that offered at least 1 MOUD, those that offered no MOUDs had lower odds of also offering psychiatric medications (odds ratio [OR], 0.06; 95% CI, 0.05-0.08; Wald χ21 = 542.09; P < .001), being licensed by a state or hospital authority (OR, 0.39; 95% CI, 0.27-0.57; Wald χ21 = 24.28; P < .001), or being accredited by a health organization (OR, 0.28; 95% CI, 0.23-0.33; Wald χ21 = 180.91; P < .001). Residential facilities that did not offer any MOUDs had higher odds of accepting cash-only payments than those that offered at least 1 MOUD (OR, 4.80; 95% CI, 3.47-6.64; Wald χ21 = 89.65; P < .001). Conclusions and Relevance: In this cross-sectional study of residential addiction treatment facilities in the United States, MOUD availability and use were sparse. Public health and policy efforts to improve access to and use of MOUDs in residential treatment facilities could improve treatment outcomes for individuals with opioid use disorder who are initiating recovery.

Trends in first-time treatment admissions for older adults with alcohol use disorder: Availability of medical and specialty clinical services in hospital, residential, and outpatient facilities.

BACKGROUND: Alcohol use disorder (AUD) is a growing problem among older adults. The aim of this study was to quantify trends in first-time treatment admissions for older adults with AUD in the U.S., and examine the medical and specialty clinical services offered by treatment facility type. METHODS: Patient level data were collected from the Treatment Episode Data Set for Admissions between 2004-2017. Joinpoint regression was used to identify unique trends in first-time treatment admissions for older adults with AUD. Provider level data were collected from the National Survey of Substance Abuse Treatment Services (N-SSATS) for the most recent year, 2017. N-SSATS data were grouped by facility type (inpatient/hospital, residential, and outpatient treatment) to examine differences in medications and clinical services. RESULTS: Among all persons seeking first-time treatment for AUD with alcohol as their primary drug of choice (n = 3,606,948), there was a significant increase in the proportion of older adults seeking treatment from 2004 to 2017 (p-trend<0.001), with an average annual percent change of 6.8% (95% confidence intervals: 6.2%-7.4%). The majority of older adults with AUD sought treatment in outpatient and residential facilities, which compared to hospital-based facilities had lower odds of offering supervised detoxification, acamprosate, naltrexone, psychiatric medications, or mental health services (all p-values<0.001). Fewer than 25% of hospital-based and 20% of residential or outpatient facilities offered specialty services for older adults. CONCLUSIONS: U.S. substance abuse treatment providers are not compensating for the changing nature of admissions by older adults, and are not providing state of the art services for this population.