Parallel modeling of pain and depression in prediction of relapse during buprenorphine and naloxone treatment: A finite mixture model.
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ABSTRACT: Background
Relapse 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.Method
The 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).Results
Results 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.Conclusion
This 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.
SUBMITTER: Vest NA
PROVIDER: S-EPMC7173998 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder. Objective:To evaluate the cost-effectiveness of buprenorphine-naloxone versus extended-release naltrexone. Design:Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U.S. inpatient or residential treatment programs. Data Sources:Study instruments. Target Population:Adults with opioid use disorder. Time Horizon:24-week intervention with an additional 12 weeks of observation. Perspective:Health care sector and societal. Interventions:Buprenorphine-naloxone and extended-release naltrexone. Outcome Measures:Incremental costs combined with incremental quality-adjusted life-years (QALYs) and incremental time abstinent from opioids. Results of Base-Case Analysis:Use of the health care sector perspective and a willingness-to-pay threshold of $100 000 per QALY showed buprenorphine-naloxone to be preferable to extended-release naltrexone in 97% of bootstrap replications at 24 weeks and in 85% at 36 weeks. Similar results were obtained with incremental time abstinent from opioids as an outcome and with use of the societal perspective. Results of Sensitivity Analysis:The base-case results were sensitive to the cost of the 2 treatments and the success of randomized treatment initiation. Limitation:Relatively short follow-up for a chronic condition, substantial missing data, no information on patient out-of-pocket and social service costs. Conclusion:Buprenorphine-naloxone is preferred to extended-release naltrexone as first-line treatment when both options are clinically appropriate and patients require detoxification before initiating extended-release naltrexone. Primary Funding Source:National Institute on Drug Abuse, National Institutes of Health.
| S-EPMC6581635 | biostudies-literature
Project description:BackgroundThis study sought to determine the relative importance of a range of Bup/Nx doses compared to Bup alone in producing subjective and reinforcing effects.MethodsHeroin-using volunteers (n=13) were transitioned onto daily oral hydromorphone (40mg). Laboratory sessions assessed the reinforcing and subjective effects of intravenous (IV) doses of Bup (1.51, 2.16, 6.15, and 8.64mg) and Bup/Nx (1.51/0.44, 2.16/0.61, 6.15/1.71, and 8.64/2.44mg). Placebo (Pbo), heroin (25mg) and Nx (0.3mg) were tested as neutral, positive, and negative controls, respectively.ResultsIV Bup alone was self-administered substantially less than IV heroin, though the two largest doses of Bup produced positive subjective effects, drug "Liking" (0-100mm), which were comparable to heroin (mean difference: Heroin vs Bup 6.15mg: -3.4mm, Heroin vs Bup 8.64mg: -11.3mm). All indicators of abuse potential seen with IV Bup alone were substantially decreased with the addition of Nx. All Bup/Nx combinations produced ratings of aversive effects, "Bad", which were comparable to, or greater than IV, Nx. On three of the four measures of aversive effects, the largest difference is seen with the 8.64 vs 8.64/2.44 condition.ConclusionsThis study further demonstrates the ability of the Bup/Nx combination to deter IV use. Although none of the Bup/Nx combinations showed indications of abuse potential, formulations with larger absolute Nx, may be less abusable as they precipitate a greater degree of withdrawal.
| S-EPMC10071507 | biostudies-literature
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| S-EPMC5506997 | biostudies-other
Project description:BackgroundSublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs).MethodsIntravenous heroin users (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions.ResultsIntravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of 'drug liking' and 'desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient.ConclusionsThese data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.
| S-EPMC3489277 | biostudies-literature
Project description:BackgroundBuprenorphine can be used for the treatment of opioid dependence in primary care settings. National guidelines recommend directly observed initial dosing followed by multiple in-clinic visits during the induction week. We offered buprenorphine treatment at a public hospital primary care clinic using a home, unobserved induction protocol.MethodsParticipants were opioid-dependent adults eligible for office-based buprenorphine treatment. The initial physician visit included assessment, education, induction telephone support instructions, an illustrated home induction pamphlet, and a 1-week buprenorphine/naloxone prescription. Patients initiated dosing off-site at a later time. Follow-up with urine toxicology testing occurred at day 7 and thereafter at varying intervals. Primary outcomes were treatment status at week 1 and induction-related events: severe precipitated withdrawal, other buprenorphine-prompted withdrawal symptoms, prolonged unrelieved withdrawal, and serious adverse events (SAEs).ResultsPatients (N = 103) were predominantly heroin users (68%), but also prescription opioid misusers (18%) and methadone maintenance patients (14%). At the end of week 1, 73% were retained, 17% provided induction data but did not return to the clinic, and 11% were lost to follow-up with no induction data available. No cases of severe precipitated withdrawal and no SAEs were observed. Five cases (5%) of mild-to-moderate buprenorphine-prompted withdrawal and eight cases of prolonged unrelieved withdrawal symptoms (8% overall, 21% of methadone-to-buprenorphine inductions) were reported. Buprenorphine-prompted withdrawal and prolonged unrelieved withdrawal symptoms were not associated with treatment status at week 1.ConclusionsHome buprenorphine induction was feasible and appeared safe. Induction complications occurred at expected rates and were not associated with short-term treatment drop-out.
| S-EPMC2628995 | biostudies-literature
Project description:A sublingual soluble-film formulation of buprenorphine/naloxone (B/N) has been approved by the US Food and Drug Administration for the treatment of opioid dependency. This preparation provides unit-dose, child-resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid-dependent volunteers. Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone-induced opioid withdrawal. Subjects were randomized to receive either B (16 mg, n = 18) or B/N (16/4 mg, n = 16) soluble films for 5 days. The primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Thirty-four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between the groups. The results support the use of B and B/N soluble films as safe and effective delivery methods for opioid induction.
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Project description:ImportanceExpanding Medicaid eligibility could affect prescriptions of buprenorphine with naloxone, an established treatment for opioid use disorder, and opioid pain relievers (OPRs).ObjectiveTo examine changes in prescriptions of buprenorphine with naloxone and OPRs after the US Affordable Care Act Medicaid expansion.Design, setting, and participantsIn this cohort study, longitudinal, patient-level, retail pharmacy claims were extracted from IQVIA real-world data from an anonymized, longitudinal, prescription database. The sample included 11.9 million individuals who filled 2 or more prescriptions for a prescription opioid during at least 1 year between January 1, 2010, and December 31, 2015, from California, Maryland, and Washington (expansion states) and Florida and Georgia (nonexpansion states). Data analysis was conducted from August 1, 2017, to May 31, 2018. Data were aggregated to county-year observations (N = 2082) and linked to county-level covariates. For each outcome, a difference-in-differences regression model was estimated comparing changes before and after expansion in expansion vs nonexpansion counties. Models were adjusted for county demographics, uninsured rate, and overdose mortality in the baseline year (2010).ExposuresPresence of Medicaid expansion in the year.Main outcomes and measuresFor buprenorphine with naloxone and OPRs, rates per 100 000 county residents were calculated separately for any prescriptions overall and by different payment sources. Mean days of medication per county among people filling prescriptions for these agents were also determined.ResultsThe study sample included 11.9 million individuals (expansion states: 40.9% men; mean [SD] age, 44.1 [13.8] years; nonexpansion states: 41.0% men; mean [SD] age, 43.7 [13.7] years). In expansion counties, 68.8 individuals per 100 000 county residents filled buprenorphine with naloxone and 5298.3 filled OPR prescriptions in 2010. After expansion, buprenorphine with naloxone fills per 100 000 county residents increased significantly in expansion relative to nonexpansion counties (8.7; 95% CI, 1.7 to 15.7). Opioid pain reliever fills per 100 000 county residents did not significantly change in expansion counties relative to nonexpansion counties (327.4; 95% CI -202.5 to 857.4). The rate of OPRs per 100 000 county residents paid for by Medicaid significantly increased (374.0; 95% CI, 258.3 to 489.7). There were no significant changes in days per 100 000 county residents of either medication after expansion.Conclusions and relevanceMedicaid expansion significantly increased buprenorphine with naloxone prescriptions per 100 000 county residents in expansion counties, suggesting that expansion improved access to opioid use disorder treatment. Expansion did not significantly increase the overall rate per 100 000 county residents of OPR prescriptions, but increased the population with OPRs paid for by Medicaid. This finding therefore suggests the growing importance of Medicaid in pain management and addiction prevention.
| S-EPMC6324520 | biostudies-literature
Project description:BackgroundExtended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX.MethodsWe initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433.FindingsBetween Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group).InterpretationIn this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications.FundingNIDA Clinical Trials Network.
| S-EPMC5806119 | biostudies-literature
Project description:AimsTo evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX).DesignRandomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119).SettingTwenty addiction treatment centers.ParticipantsAdult out-patients (ages 18-65) with DSM-IV-TR opioid dependence.MeasurementsThe primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF).FindingsThe BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)].ConclusionsCompared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets.
| S-EPMC4669043 | biostudies-literature
Project description:BackgroundSeptic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class.MethodsPatients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset.ResultsA total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion.ConclusionsSeptic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.
| S-EPMC8273991 | biostudies-literature