Prescription Opioid Use Disorder Research Articles

Patients’ perspectives on tapering programmes for prescription opioid use disorder: a qualitative study

ObjectivesApproximately 10% of chronic pain patients who receive opioids develop an opioid use disorder (OUD). Tapering programmes for these patients show high drop-out rates. Insight into chronic pain patients’ experiences...

ADX106772, an mGlu2 receptor positive allosteric modulator, selectively attenuates oxycodone taking and seeking

Opioid abuse and overdose have risen to epidemic proportions in the United States. Oxycodone is the most abused prescription opioid. Treatments for opioid use disorder (OUD) seek to reduce vulnerability to relapse by reducing sources of reinforcement to seek drug (i.e., acute drug effects or drug withdrawal/craving). Accumulating evidence that glutamate release elicits drug-seeking behaviors has generated interest in pharmacotherapies targeting the glutamate system. Agonists and positive allosteric modulators of the metabotropic glutamate 2 (mGlu2) receptor decrease glutamate activity, reducing drug taking and seeking. The present study tested whether the mGlu2 receptor positive allosteric modulator ADX106772 reduces oxycodone self-administration and the conditioned reinstatement of oxycodone seeking without affecting behaviors directed toward a highly palatable nondrug reinforcer (sweetened condensed milk). Male Wistar rats were trained to self-administer oxycodone (0.15 mg/kg/infusion, i.v., 12 h/day) or sweetened condensed milk (SCM; diluted 2:1 v/v in H2O, orally, 30 min/day) for 13 days in the presence of a contextual/discriminative stimulus (SD), and the ability of ADX106772 (0, 0.3, 1, 3 and-10 mg/kg, s. c.) to decrease self-administration was tested. The rats then underwent extinction training, during which oxycodone, SCM, and the SD were withheld. After extinction, the ability of ADX106772 to prevent SD-induced conditioned reinstatement of oxycodone and SCM seeking was tested. ADX106772 reduced oxycodone self-administration and conditioned reinstatement without affecting SCM self-administration or conditioned reinstatement. ADX106772 reduced oxycodone taking and seeking and did not affect the motivation for the palatable conventional reinforcer, SCM, suggesting that activating mGlu2 receptors with a positive allosteric modulator is a potential approach for prescription OUD treatment.

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats.

Background: The Department of Health and Human Services reports that prescription pain reliever (e.g., oxycodone) misuse was initiated by 4,400 Americans each day in 2019. Amid the opioid crisis, effective strategies to prevent and treat prescription opioid use disorder (OUD) are pressing. In preclinical models, the orexin system is recruited by drugs of abuse, and blockade of orexin receptors (OX receptors) prevents drug-seeking behavior. The present study sought to determine whether repurposing suvorexant (SUV), a dual OX receptor antagonist marketed for the treatment of insomnia, can treat two features of prescription OUD: exaggerated consumption and relapse. Methods: Male and female Wistar rats were trained to self-administer oxycodone (0.15mg/kg, i. v., 8h/day) in the presence of a contextual/discriminative stimulus (SD) and the ability of SUV (0-20mg/kg, p. o.) to decrease oxycodone self-administration was tested. After self-administration testing, the rats underwent extinction training, after which we tested the ability of SUV (0 and 20mg/kg, p. o.) to prevent reinstatement of oxycodone seeking elicited by the SD. Results: The rats acquired oxycodone self-administration and intake was correlated with the signs of physical opioid withdrawal. Additionally, females self-administered approximately twice as much oxycodone as males. Although SUV had no overall effect on oxycodone self-administration, scrutiny of the 8-h time-course revealed that 20mg/kg SUV decreased oxycodone self-administration during the first hour in males and females. The oxycodone SD elicited strong reinstatement of oxycodone-seeking behavior that was significantly more robust in females. Suvorexant blocked oxycodone seeking in males and reduced it in females. Conclusions: These results support the targeting of OX receptors for the treatment for prescription OUD and repurposing SUV as pharmacotherapy for OUD.

Patients’ Perspectives on the Development of Prescription Opioid Use Disorder in Patients with Chronic Non-Cancer Pain

Introduction: In the past decade, prescription opioid use increased exponentially and concomitantly opioid use disorders (OUD) are becoming more common. Several risk factors for developing OUD have been identified, but little is known regarding the patients’ perspective on developing a prescription OUD. Methods: We recruited 25 adults undergoing treatment for prescription OUD. In-depth, semi-structured interviews focussed on experiences with long-term opioid use, knowledge and attitudes regarding opioids, and access to opioids. A directed content analysis was conducted on the transcribed interviews using NVivo. Results: Participants showed that the development of an OUD is affected by various factors which could be grouped into three themes: (1) experiences driving initiation, (2) experiences driving continuation, and (3) experiences with prescription OUD. Besides the need for pain management, the dynamics of patient-provider communication, care coordination, provider vigilance, and environmental support all contributed to the way patients used their opioids. Conclusion: Patients’ experiences illustrate that the first stage of the development of prescription OUD differs from the development of other substance addictions. Negative reinforcement might play a more prominent role in the early phase of prescription opioid use. Patients expressed a lack of guidance, both at the start of use and long-term use, easy access to new prescriptions and a lack of monitoring as main drivers of the development. Poorly controlled pain and subjective stress fuelled continuous opioid use.

What is the benefit of inconsistent opioid agonist treatment in patients with prescription opioid use disorder?

IntroductionStudies consistently show that patients with prescription opioid use disorder (OUD) respond to buprenorphine treatment. Few studies have followed these patients in the long-term. Our longitudinal research has shown opioid abstinence to be associated most strongly with opioid agonist/partial agonist treatment. We also found that many patients used agonist treatment inconsistently; questions remain about the benefits of intermittent opioid agonist treatment.ObjectivesWe examined patients during the 3.5 years following their entry into a 3-month trial of treatment for prescription OUD. The current analysis compared opioid use outcomes among patients who reported receipt of agonist treatment consistently, inconsistently, or never.MethodsThis secondary analysis (N=309) of a U.S. multi-site randomized controlled trial of treatment for prescription OUD assessed variability in receiving opioid agonist treatment during the 3.5-year follow-up period, and the association between agonist treatment and opioid abstinence. Assessments were collected at months 18, 30, and 42 following treatment entry; patients were asked if they were currently taking agonist treatment and whether they had used other opioids in the previous month. Patients with only one follow-up assessment (n=29) were excluded from this analysis.ResultsMost patients reported current opioid abstinence on at least one follow-up visit: 38% were always abstinent, 41% sometimes, and 21% never. Twenty-three percent always reported currently using agonist treatment, 26% sometimes, and 51% never. Patients consistently reporting agonist use were most likely to always be opioid-abstinent in the past month (69%), with 25% sometimes and 6% never abstinent. Patients who never reported agonist use were equally likely to be abstinent never (32%), sometimes (35%), and always (32%). Patients who sometimes reported receiving agonists were most likely to report abstinence sometimes (65%); 14% never reported abstinence, and 21% always did.Those consistently receiving agonist treatment were more likely to always be opioid-abstinent (69%) than those sometimes (21%) or never (32%) receiving agonists. Those never receiving agonist treatment were more likely to never report opioid abstinence (32%) than were those sometimes (14%) or always (6%) receiving agonists. Interestingly, those who sometimes received agonists were more likely to be abstinent than those who never received agonists: those who sometimes received agonists were more likely to be abstinent sometimes than those who never received agonists (65% vs. 35%) and less likely to never be abstinent than were those who never received agonists (14% vs. 32%).ConclusionsReceiving opioid agonist treatment has been shown to be associated with opioid abstinence during long-term follow-up. This study shows that even those who only inconsistently receive agonists are also likely to benefit.Disclosure of InterestR. Weiss Consultant of: Alkermes, M. Griffin: None Declared

Assessing Opioid Abuse in Chronic Pain Patients: Further Validation of the Prescription Opioid Misuse Index (POMI) Using Item Response Theory

AbstractDue the limitations of the previous validations, the purpose of this study was to further validate the Prescription Opioid Misuse Index (POMI) in a larger sample of chronic non-cancer pain (CNCP) patients and to examine differential item functioning (DIF) across sex. Participants (n=225 CNCP patients under long-term opioid therapy) completed patient characteristics, self-reported POMI and DSM-5 prescription opioid use disorder measurements. Reliability and factor structure were assessed using both item response theory and classical test theory. ROC curve analysis was used to establish the optimum cut-off score for detecting the presence of DSM-5 prescription opioid-use disorder. Concurrent validity was also tested. The POMI showed a unidimensional factor structure and acceptable internal consistency (ωcat =0.62). DIF analysis showed that males and females respond similarly to each item of the POMI, supporting unbiased measurement of the latent trait across both groups. A cut-off point of 2 is suggested in order to maximize the accuracy of the instrument as a first-screening tool for opioid misuse (AUC=0.78; p<0.001; CI 95%: 0.72–0.85). Concurrent validity of the POMI was high with DSM-5 moderate to severe opioid-use disorder criteria (OR=7.824, p<0.001). These results indicate that the POMI is a valid and clinically feasible screening instrument for detecting CNCP patients who misuse opioid medications. The short length of the scale could meet the needs of clinical practice as it allows clinicians to precisely identify and monitor prescription opioid misuse in both male and female patients.

Prefrontal cortical response to natural rewards and self-reported anhedonia are associated with greater craving among recently withdrawn patients in residential treatment for opioid use disorder

Both anhedonia and craving are common among patients with opioid use disorder (OUD), and are associated with vulnerability to relapse. Although these constructs are theoretically linked relatively few studies have examined them together. In the current study, recently withdrawn patients (N = 71) in residential treatment for prescription OUD underwent a cue reactivity paradigm while being monitored with functional near-infrared spectroscopy (fNIRS). Patients also self-reported symptoms of anhedonia via the Snaith-Hamilton Pleasure Scale (SHAPS), while smartphone-based ecological momentary assessments (EMA) were used to measure craving levels. On average, lower right prefrontal cortex (PFC) activity in response to positive social stimuli was associated with higher craving (β = − 2.87; S.E. = 1.23; p = 0.02). Self-reported anhedonia moderated the association between PFC activity and craving (β = − 1.02; S.E. = 0.48; p = 0.04), such that patients with two or more anhedonic symptoms had a significant and stronger negative association between PFC activation to hedonically positive images and craving, compared to patients with fewer than two anhedonic symptoms, among whom the association was not significant. This finding provides evidence that higher levels of anhedonia among patients in residential treatment for OUD are associated with a stronger link between lower PFC response to positive social experiences and higher levels of craving, potentially increasing overall vulnerability to relapse.

Diagnosing Prescription Opioid Use Disorder in Patients Using Prescribed Opioids for Chronic Pain.

The diagnostic criteria for opioid use disorder, originally developed for heroin, did not anticipate the surge in prescription opioid use and the resulting complexities in diagnosing prescription opioid use disorder (POUD), including differentiation of pain relief (therapeutic intent) from more common drug use motives, such as to get high or to cope with negative affect. The authors examined the validity of the Psychiatric Research Interview for Substance and Mental Disorders, DSM-5 opioid version, an instrument designed to make this differentiation. Patients (N=606) from pain clinics and inpatient substance treatment who ever received a ≥30-day opioid prescription for chronic pain were evaluated for DSM-5 POUD (i.e., withdrawal and tolerance were not considered positive if patients used opioids only as prescribed, per DSM-5 guidelines) and pain-adjusted POUD (behavioral/subjective criteria were not considered positive if pain relief [therapeutic intent] was the sole motive). Bivariate correlated-outcome regression models indicated associations of 10 validators with DSM-5 and pain-adjusted POUD measures, using mean ratios for dimensional measures and odds ratios for binary measures. The prevalences of DSM-5 and pain-adjusted POUD, respectively, were 44.4% and 30.4% at the ≥2-criteria threshold and 29.5% and 25.3% at the ≥4-criteria threshold. Pain adjustment had little effect on prevalence among substance treatment patients but resulted in substantially lower prevalence among pain treatment patients. All validators had significantly stronger associations with pain-adjusted than with DSM-5 dimensional POUD measures (ratios of mean ratios, 1.22-2.31). For most validators, pain-adjusted binary POUD had larger odds ratios than DSM-5 measures. Adapting POUD measures for pain relief (therapeutic intent) improved validity. Studies should investigate the clinical utility of differentiating between therapeutic and nontherapeutic intent in evaluating POUD diagnostic criteria.

Use of Medication for Opioid Use Disorder Among US Adolescents and Adults With Need for Opioid Treatment, 2019

Medication for opioid use disorder (MOUD) is the criterion standard treatment for opioid use disorder (OUD), but nationally representative studies of MOUD use in the US are lacking. To estimate MOUD use rates and identify associations between MOUD and individual characteristics among people who may have needed treatment for OUD. Cross-sectional, nationally representative study using the 2019 National Survey on Drug Use and Health in the US. Participants included community-based, noninstitutionalized adolescent and adult respondents identified as individuals who may benefit from MOUD, defined as (1) meeting criteria for a past-year OUD, (2) reporting past-year MOUD use, or (3) receiving past-year specialty treatment for opioid use in the last or current treatment episode. The main outcomes were treatment with MOUD compared with non-MOUD services and no treatment. Associations with sociodemographic characteristics (eg, age, race and ethnicity, sex, income, and urbanicity); substance use disorders; and past-year health care or criminal legal system contacts were analyzed. Multinomial logistic regression was used to compare characteristics of people receiving MOUD with those receiving non-MOUD services or no treatment. Models accounted for predisposing, enabling, and need characteristics. In the weighted sample of 2 206 169 people who may have needed OUD treatment (55.5% male; 8.0% Hispanic; 9.9% non-Hispanic Black; 74.6% non-Hispanic White; and 7.5% categorized as non-Hispanic other, with other including 2.7% Asian, 0.9% Native American or Alaska Native, 0.2% Native Hawaiian or Pacific Islander, and 3.8% multiracial), 55.1% were aged 35 years or older, 53.7% were publicly insured, 52.2% lived in a large metropolitan area, 56.8% had past-year prescription OUD, and 80.0% had 1 or more co-occurring substance use disorders (percentages are weighted). Only 27.8% of people needing OUD treatment received MOUD in the past year. Notably, no adolescents (aged 12-17 years) and only 13.2% of adults 50 years and older reported past-year MOUD use. Among adults, the likelihood of past-year MOUD receipt vs no treatment was lower for people aged 50 years and older vs 18 to 25 years (adjusted relative risk ratio [aRRR], 0.14; 95% CI, 0.05-0.41) or with middle or higher income (eg, $50 000-$74 999 vs $0-$19 999; aRRR, 0.18; 95% CI, 0.07-0.44). Compared with receiving non-MOUD services, receipt of MOUD was more likely among adults with at least some college (vs high school or less; aRRR, 2.94; 95% CI, 1.33-6.51) and less likely in small metropolitan areas (vs large metropolitan areas, aRRR, 0.41; 95% CI, 0.19-0.93). While contacts with the health care system (85.0%) and criminal legal system (60.5%) were common, most people encountering these systems did not report receiving MOUD (29.5% and 39.1%, respectively). In this cross-sectional study, MOUD uptake was low among people who could have benefited from treatment, especially adolescents and older adults. The high prevalence of health care and criminal legal system contacts suggests that there are critical gaps in care delivery or linkage and that cross-system integrated interventions are warranted.

Resting State EEG Activity Related to Impulsivity in People with Prescription Opioid Use Disorder

Previous studies on EEG activity in prescription opioid use disorder (OUD) have reported neuronal dysfunction related to heroin use, most consistently reflected by increases in β-brain oscillations. As similar research has yet to examine EEG associated with non-medical use of prescription opioid and as inhibitory deficits are associated with OUD, this pilot study compared quantitative EEGs of 18 patients with prescription OUD and 18 healthy volunteers and assessed relationships between oscillatory activity and impulsivity with the Barratt Impulsiveness Scale (BIS-11). Spectral EEGs showed greater amplitude density in β1, β2, and β3 frequencies across frontal, temporal-central and posterior recording areas in patients. Similar abnormal amplitude density increases were seen in δ but not in θ or α frequency bands. Patients exhibited greater scores (impaired impulse control) on BIS-11 subscales (attention, motor, self-control) and impairment of these impulsive subtypes was associated with increases in β and δ oscillations. In patients, β1, β2, and δ activity was positively associated with disorder severity. Taken together, the results suggest that altered brain oscillations in persons with prescription OUD show some similarities with reported oscillatory changes in heroin use and may indicate a chronic state of imbalance in neuronal networks regulating impulsive and inhibitory control systems.

Buprenorphine/naloxone versus methadone opioid rotation in patients with prescription opioid use disorder and chronic pain: study protocol for a randomized controlled trial

BackgroundOpioids are effective in pain-management, but long-term opioid users can develop prescription opioid use disorder (OUD). One treatment strategy in patients with OUD is rotating from a short-acting opioid to a long-acting opioid (buprenorphine/naloxone (BuNa) or methadone). Both BuNa and methadone have been shown to be effective strategies in patients with OUD reducing opioid misuse, however data on head-to-head comparison in patients with chronic non-malignant pain and prescription OUD are limited.MethodsThis two-armed open-label, randomized controlled trial aims to compare effectiveness between BuNa and methadone in patients with chronic non-malignant with prescription OUD (n = 100). Participants receive inpatient rotation to either BuNa or methadone with a flexible dosing regimen. The primary outcome is opioid misuse 2 months after rotation. Secondary outcomes include treatment compliance, side effects, analgesia, opioid craving, quality of life, mood symptoms, cognitive and physical functioning over 2- and 6 months follow-up. Linear mixed model analysis will be used to evaluate change in outcome parameters over time between the treatment arms.DiscussionThis is one of the first studies comparing buprenorphine/naloxone and methadone for treating prescription OUD in a broad patient group with chronic non-malignant pain. Results may guide future treatment for patients with chronic pain and prescription OUD.Trial registrationhttps://www.trialregister.nl/, NL9781

Treatment-seeking behaviour among people with opioid use disorder in the high-income countries: A systematic review and meta-analysis.

To determine treatment seeking behaviour in those with opioid use disorder (OUD) in the high-income countries. Five databases were searched in November 2019 for quantitative studies that reported OUD treatment seeking behaviour. Data analysis involved determining an overall pooled proportion estimate of treatment seeking behaviour for the two base groups, lifetime treatment and past 12-month or less treatment using the IVhet effect model. Subgroup analysis included heroin OUD, prescription OUD and general OUD. The sensitivity analysis included removal of outliers, separating adults and adolescents and the metaXL sensitivity analysis (studies are excluded if outside the pooled proportion confidence interval of the base case). Systematic review Prospero database registration number [CRD42020159531]. There were 13 quantitative studies included in the systematic review, with all studies being from the United States of America (USA). IVhet models showed that 40% (95% CI: 23%, 58%) and 21% (95% CI: 16%, 26%) sought treatment in their lifetime and past 12 months respectively. Sub-group analysis found that lifetime treatment seeking for prescription OUD, 29% (95% CI: 27%, 31%), was less than for heroin plus combined OUD, 54% (95% CI: 26%, 82%). Most of the pooled results had high heterogeneity statistics except for results of lifetime treatment seeking for prescription OUD and past 12-month treatment seeking for prescription OUD. All included studies in this meta-analysis were from the USA and indicate modest levels of treatment seeking for those with OUD. In particular, this review found that in the USA one in five people with OUD sought OUD treatment in the previous 12 months and two in five people with OUD sought OUD treatment in their lifetime. Further research is urgently required to explore the barriers and facilitators that can improve this low treatment seeking in those with OUD.

Examining differences in prescription opioid use behaviors among U.S. adults with and without disabilities

We aimed to identify differences in prescription opioid-related behaviors between adults with and without disabilities in the U.S. We analyzed data from the 2015–2017 National Survey on Drug Use and Health (128,740 individuals; weighted N of 244,831,740) to examine disability-based differences in (1) reasons and sources of last prescription opioid misuse and, in multivariate models overall and stratified by disability, the likelihood of (2) prescription opioid use, and if used, (3) misuse and prescription opioid use disorder (OUD), overall and stratified by disability. Adults with disabilities were 11% more likely than adults without disabilities to report any past-year prescription opioid use, adjusted for sociodemographic, health, and behavioral health characteristics. However, among adults with any prescription opioid use, which is more common among people with disabilities, likelihood of prescription OUD did not vary by disability status. Pain relief as the reason for last misuse was associated with 18% increased likelihood of prescription OUD, if any use. To reduce risk of opioid misuse among people with disabilities, accessible and inclusive chronic pain management services are essential. Further, the substance use treatment field should provide accessible and inclusive services, and be aware of the need for pain management by many people with disabilities, which may include the use of prescription opioids. These findings highlight essential opportunities for public health and policies to improve access, accommodations, and quality of health and behavioral health care for people with disabilities, and to encourage a holistic perspective of people with disabilities and their needs.

Reregulation of cortisol levels and sleep in patients with prescription opioid use disorder during long-term residential treatment

ObjectiveResearch has demonstrated that hypothalamic-pituitary-adrenal (HPA) axis function and sleep patterns are dysregulated in patients diagnosed with opioid use disorder (OUD). It is unclear whether and/or when cortisol and sleep might re-regulate over time, and, whether re-regulation is associated with abstinence following discharge from residential treatment. The current study evaluated changes in sleep and basal cortisol levels in prescription OUD patients in residential treatment, and the association between these measures and treatment outcome following discharge. MethodAs part of a larger study, 55 participants with prescription OUD provided two days of salivary cortisol samples and 12 consecutive nights of sleep actigraphy between days 19–30 of residential treatment (Time Point 1; TP1). Thirteen of the original 55 participants remained in residence and repeated the measures between days 60–72 (Time Point 2; TP2). Thirty-seven healthy controls (HC) provided baseline measures (TP1) of salivary cortisol and sleep. Treatment outcome data, abstinence vs relapse, were established at 120 days following discharge. ResultsPrescription OUD patients had higher cortisol levels and lower total sleep time (TST) than HC at TP1. At TP2, TST and cortisol levels no longer differed from HCs in the subgroup of patients who remained abstinent following discharge after TP2. Individuals whose cortisol and TST did not change from TP1 to TP2 were more likely to relapse following discharge from residential treatment. ConclusionRe-regulation of TST and cortisol levels while in residential treatment was associated with better treatment outcome following discharge for prescription OUD patients.

Clinical and psychological factors associated with interdose opioid withdrawal in chronic pain population

BackgroundThe DSM-5 diagnostic criteria for Prescription Opioid-Use Disorder (POUD) have undergone some significant changes. One of the most controversial changes has been the elimination of the withdrawal symptoms criterion when opioid use is under appropriate medical supervision. For this reason, the goal of this study was to analyze factors associated with opioid withdrawal in patients with chronic non-cancer pain (CNCP). MethodsThis cross-sectional descriptive study involved 404 patients who use prescription opioids for long-term treatment (≥90 days) of CNCP. Measures included sociodemographic and clinical characteristics, POUD, withdrawal symptoms, craving, anxiety-depressive symptoms, and pain intensity and interference. ResultsForty-seven percent (n = 193) of the sample reported moderate-severe withdrawal symptoms, which were associated with lower age, higher daily morphine dose and duration of treatment with opioids, moderate-severe POUD, use of psychotropic drugs, higher anxiety-depressive symptoms, and greater pain intensity and interference (p < .05). Binary logistic regression analysis showed that moderate-severe POUD (OR = 2.82), anxiety (OR = 2.21), depression (OR = 1.81), higher pain interference (OR = 1.05), and longer duration of treatment with opioids were the strongest factors associated with moderate-severe withdrawal symptoms (p < .05). ConclusionPsychological factors seem to play a key role in the severity of withdrawal symptoms. Since greater intensity of these symptoms increases the risk of developing POUD, knowing the factors associated with withdrawal may be useful in developing preventive psychological interventions.

Neural responses to negative events and subsequent persistence behavior differ in individuals recovering from opioid use disorder compared to controls

ABSTRACT Background: Negative emotion is associated with substance craving and use in individuals recovering from substance use disorders, including prescription opioid use disorder (POUD). Decisions to abandon or persist towards a goal after negative emotion-eliciting events, and neural responses that shape such decisions, may be important in maintaining recovery from POUD. Objectives: We examined differences in neural responses to negative events and subsequent persistence decisions in individuals recovering from POUD without a history of a substance use disorder. Methods: 20 individuals with POUD (POUD group: 4 females, abstinent 2–3 weeks after admission to an inpatient treatment facility post-detoxification, no other substance use disorder), and 20 individuals with no substance use history (control group: 6 females) completed a persistence-after-setbacks task during functional magnetic resonance imaging. Participants advanced along a path toward a reward; after encountering each negative event (i.e., progress-erasing setback), participants made decisions to persist or abandon the path. Persistence decision rates were compared between groups and blood-oxygen-level-dependent signal to negative events was analyzed within a striatum region of interest (ROI) as well as whole-brain. Results: The POUD group persisted less (t(38) = 2.293, p = .028, d = .725) and showed lower striatum (left ventral putamen) signal to negative events compared to the control group (p < .05, corrected for striatum ROI). Conclusions: In POUD, neural and behavioral responses to negative events differ from controls. These differences are a target for research to address whether POUD treatment increases persistence and striatum responses to negative events and improves recovery outcomes.

Structural MRI and functional connectivity features predict current clinical status and persistence behavior in prescription opioid users

Prescription opioid use disorder (POUD) has reached epidemic proportions in the United States, raising an urgent need for diagnostic biological tools that can improve predictions of disease characteristics. The use of neuroimaging methods to develop such biomarkers have yielded promising results when applied to neurodegenerative and psychiatric disorders, yet have not been extended to prescription opioid addiction. With this long-term goal in mind, we conducted a preliminary study in this understudied clinical group. Univariate and multivariate approaches to distinguishing between POUD (n = 26) and healthy controls (n = 21) were investigated, on the basis of structural MRI (sMRI) and resting-state functional connectivity (restFC) features. Univariate approaches revealed reduced structural integrity in the subcortical extent of a previously reported addiction-related network in POUD subjects. No reliable univariate between-group differences in cortical structure or edgewise restFC were observed. Contrasting these mixed univariate results, multivariate machine learning classification approaches recovered more statistically reliable group differences, especially when sMRI and restFC features were combined in a multi-modal model (classification accuracy = 66.7%, p < .001). The same multivariate multi-modal approach also yielded reliable prediction of individual differences in a clinically relevant behavioral measure (persistence behavior; predicted-to-actual overlap r = 0.42, p = .009). Our findings suggest that sMRI and restFC measures can be used to reliably distinguish the neural effects of long-term opioid use, and that this endeavor numerically benefits from multivariate predictive approaches and multi-modal feature sets. This can serve as theoretical proof-of-concept for future longitudinal modeling of prognostic POUD characteristics from neuroimaging features, which would have clearer clinical utility.

Chronic prescription opioid use predicts stabilization on buprenorphine for the treatment of opioid use disorder

IntroductionPrescription opioid misuse is a risk factor for opioid use disorder (OUD). Patients who misuse prescribed opioids and those who misuse illicit opioids are demographically and medically distinct groups, and research has shown there is heterogeneity in treatment response between these groups. The objective of this study was to measure the adjusted odds of successful stabilization on buprenorphine in patients with baseline prescription opioid use compared to those not prescribed opioids. MethodsA cohort of patients newly prescribed a buprenorphine product indicated for OUD between January 1 and November 30, 2018, were identified from the Texas Prescription Monitoring Program. We excluded those under the age of 15 and those who filled an opioid prescription after initiating buprenorphine to limit misclassification. We then stratified the cohort based on type of prescription opioid use in the pre-index period. We defined chronic opioid use as being prescribed opioids for a period of 90 out of 120 days, ending no sooner than 90 days prior to treatment initiation. We defined acute opioid use as filling any opioid prescription in the 90 days prior to initiating buprenorphine. The outcome of interest—stabilization on buprenorphine—was met by filling two prescriptions totaling 30-days' supply with no more than a six-day gap in therapy. We used multiple logistic regression to estimate the odds of stabilization in the prescription opioid use categories compared to those with no pre-index, opioid prescriptions. ResultsAmong 6756 eligible patients, 44.1% used prescription opioids in the 90 days prior to buprenorphine initiation. Of these, 62.2% met the criteria for acute prescription opioid use and 37.8% for chronic prescription opioid use. Patients with prescription opioid use at baseline were more likely to be older and insured compared to those with no prescription opioid use. After adjustment for covariates, both prescription opioid use groups were significantly more likely to be successfully stabilized on therapy (Acute: aOR = 1.53, 95% CI = 1.37–1.72; Chronic: aOR = 2.43, 95% CI = 2.08–2.85). In a second model, those with chronic prescription opioid use were significantly more likely than those with acute prescription opioid use to be successfully stabilized (aOR = 1.60, 95% CI = 1.31–1.90). ConclusionPersistence to buprenorphine treatment for OUD is, in part, dependent on baseline prescription opioid use. This study suggests that patients with chronic prescription opioid use may be more likely than nonprescription opioid users to be successfully stabilized on treatment and may thus benefit more from pharmacotherapy with buprenorphine than those with no prescription opioid use. Failing to account for this variation in future studies of buprenorphine treatment persistence may lead to significant residual confounding and biased results. Extending access to buprenorphine among those with prescription OUD may have a significant impact on opioid related morbidity and mortality.

Assessment of Work Loss Associated With Prescription-Related Opioid Use Disorder: A Retrospective Analysis of Claims Data.

Quantify work loss and costs associated with prescription opioid use disorder (OUD) from the employer perspective. Retrospective claims analysis to compare missed work days and associated costs between employees with and without an OUD diagnosis in a 12-month period. Two thousand three hundred eleven matched-pairs of employees were compared. The mean (SD) number of days missed while waiting for disability benefits (0.24 [1.4] vs 0.17 [1.0]; P = 0.035), absenteeism due to disability claims (9.5 [40.9] vs 5.6 [30.0]; P < 0.001), and medical visits (17.8 [18.5] vs 10.0 [12.4]; P < 0.001) was higher for employees with OUD compared with those without, resulting in higher mean (SD) indirect cost estimates of $8193 ($14,694) per employee (OUD) versus $5438 ($13,683) per employee (no OUD) (P < 0.001). Prescription OUD is associated with significant work loss and may pose considerable economic burden on employers.

Parallel modeling of pain and depression in prediction of relapse during buprenorphine and naloxone treatment: A finite mixture model

BackgroundRelapse is common in treatment for opioid use disorders (OUDs). Pain and depression often co-occur during OUD treatment, yet little is known about how they influence relapse among patients with a primary diagnosis of prescription opioid use disorder (POUD). Advanced statistical analyses that can simultaneously model these two conditions may lead to targeted clinical interventions. MethodThe objective of this study was to utilize a discrete survival analysis with a growth mixture model to test time to prescription opioid relapse, predicted by parallel growth trajectories of depression and pain, in a clinical sample of patients in buprenorphine/naloxone treatment. The latent class analysis characterized heterogeneity with data collected from the National Institute of Drug Abuse Clinical Trials Network project (CTN-0030). ResultsResults suggested that a 4-class solution was the most parsimonious based on global fit indices and clinical relevance. The 4 classes identified were: 1) low relapse, 2) high depression and moderate pain, 3) high pain, and 4) high relapse. Odds ratios for time-to-first use indicated no statistically significant difference in time to relapse between the high pain and the high depression classes, but all other classes differed significantly. ConclusionThis is the first longitudinal study to characterize the influence of pain, depression, and relapse in patients receiving buprenorphine and naloxone treatment. These results emphasize the need to monitor the influence of pain and depression during stabilization on buprenorphine and naloxone. Future work may identify appropriate interventions that can be introduced to extend time-to-first prescription opioid use among patients.