Optimal dose of buprenorphine in opioid use disorder treatment: a review of pharmacodynamic and efficacy data

Hjelmström, Peter; Nordbeck, Elin Banke; Tiberg, Fredrik

doi:10.1080/03639045.2019.1706552

Cited by 23 publications

(19 citation statements)

References 56 publications

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“…However, the overall absence of association of BUP-NX dose with retention is in line with a relatively recent review that did not find associations between higher doses and retention in treatment. 27 This may partly stem from the flexible dosing approach in the present trial and the possibility that participants with higher risk of negative outcomes were more likely to require higher buprenorphine dosage. Although BUP is a partial µ-opioid receptor agonist, its most potent effects seem to occur in doses ranging from 4 to 16 mg/day of BUP, conferring a potential dose-ceiling effect.…”

Section: Discussionmentioning

confidence: 97%

Associations of methadone and buprenorphine‐naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription‐type opioid use disorders: Exploratory analyses of the OPTIMA study

et al. 2023

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Background and ObjectivesBuprenorphine/naloxone (BUP‐NX) and methadone are used to treat opioid use disorder (OUD), yet there is insufficient evidence on the impact of doses on interventions' effectiveness and safety when treating OUD attributable to other opioids than heroin.MethodsWe explored associations between methadone and BUP‐NX doses and treatment outcomes using data from OPTIMA, a 24‐week, pragmatic, open‐label, multicenter, pan‐Canadian, randomized controlled, two‐arm parallel trial with participants (N = 272) with OUD who primarily use opioids other than heroin. Participants were randomized to receive flexible take‐home BUP‐NX (n = 138) or standard supervised methadone treatment (n = 134). We examined associations between highest BUP‐NX and methadone doses, and (1) percentage of opioid‐positive urine drug screens (UDS); (2) retention in the assigned treatment; and (3) adverse events (AEs).ResultsThe mean (SD) highest BUP‐NX and methadone dose were 17.31 mg/day (8.59) and 67.70 mg/day (34.70). BUP‐NX and methadone doses were not associated with opioid‐positive UDS percentages or AEs. Methadone dose was associated with higher retention in treatment (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.010; 1.041), while BUP‐NX dose was not (OR: 1.055; 95% CI: 0.990; 1.124). Higher methadone doses (70–110 mg/day) offered higher odds of treatment retention.Discussion and ConclusionMethadone dose was associated with higher retention, which may be related to its full µ‐opioid receptor agonism. Future research should notably ascertain the effect of pace of titration on a wide range of outcomes.Scientific SignificanceOur results extend previous findings of high doses of methadone increasing retention to be applied in our population using opioids other than heroin, including highly potent opioids.

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Section: Discussionmentioning

confidence: 97%

Associations of methadone and buprenorphine‐naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription‐type opioid use disorders: Exploratory analyses of the OPTIMA study

et al. 2023

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“…Furthermore, results from a secondary analysis of adults with OUD receiving BUP and methadone (Hser et al 2014 ) support that BUP daily doses over 16 mg and methadone daily doses above 60 mg were significantly associated with higher retention in treatment over 24 weeks (Hser et al 2014 ). Nevertheless, a recent systematic review found no conclusive evidence on the association of BUP daily dose with treatment outcomes (Hjelmström et al 2020 ). The systematic review concluded adjusting BUP maintenance dose according to clinical response, i.e., opioid use, may be optimal compared to dose adjustment in response to signs and symptoms of withdrawal and craving (Hjelmström et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, a recent systematic review found no conclusive evidence on the association of BUP daily dose with treatment outcomes (Hjelmström et al 2020 ). The systematic review concluded adjusting BUP maintenance dose according to clinical response, i.e., opioid use, may be optimal compared to dose adjustment in response to signs and symptoms of withdrawal and craving (Hjelmström et al 2020 ). This may suggest a difference in the BUP doses required to suppress craving compared to doses required to suppress opioid use over time.…”

Section: Discussionmentioning

confidence: 99%

Lower buprenorphine elimination rate constant is associated with lower opioid use

et al. 2022

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Background Opioid craving is suggested to correlate with the rate of reduction in buprenorphine (BUP) plasma levels. No studies explored Buprenorphine elimination rate constant (BUP EL.R) as a predictor of opioid use or retention in BUP treatment. Methods Analysis was performed using data from a randomized controlled trial of 141 adults with opioid use disorder (OUD) randomized to Incentivized Adherence and Abstinence monitoring (I-AAM; experimental (n = 70) and treatment-as-usual; control (n = 71). In the I-AAM, structured access to unsupervised BUP doses was provided up to 28 days contingent of adherence measured by Therapeutic Drug Monitoring and abstinence by Urinary Drug Screens (UDS). In contrast, the treatment-as-usual (control) provided unstructured access to unsupervised doses was provided for up to 14 days considering UDS results. The primary outcome was percentage negative UDS. The secondary outcome, retention in treatment, was continuous enrollment in the study and analysis was via intention-to-treat. Significant bivariate correlations with the outcomes were adjusted for group allocation. Results A significant negative correlation between BUP EL.R and percentage negative opioid screens (Pearson correlation coefficient − 0.57, p < 0.01) was found. After adjusting for trial group, BUP EL.R was shown to be an independent predictor of percentage negative opioid screens (Standardized Beta Coefficient − 0.57, 95% CI − 221.57 to − 97.44, R2 0.322). Conclusion BUP EL.R predicted 32.2% of the variation in percentage negative opioid UDS and may serve as a potential promising tool in precision medicine of BUP treatment. Higher buprenorphine elimination is associated with higher positive opioid urine screens during treatment. Trial registration ISRCTN41645723 retrospectively registered on 15/11/2015.

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“…Although there is extensive research in the area of precision medicine to improve individualized medication-assisted treatment of OUD [53], to date research has failed to provide clear evidence for certain patients characteristics or genomic profiles to predict response to methadone or buprenorphine treatment. In addition, the optimal buprenorphine dose (over 8 mg sublingual) to ensure opioid receptor blockade has also still to be defined [65]. Despite advances in the pharmacological management of OUD, entry into, induction of, and adherence to treatment remain important tasks [66].…”

Section: Discussionmentioning

confidence: 99%

Novel Long-Acting Buprenorphine Medications for Opioid Dependence: Current Update

Soyka¹

2020

Pharmacopsychiatry

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Opioid maintenance treatment with oral methadone or sublingual buprenorphine is the first-line treatment in opioid dependence. Three novel long-acting buprenorphine formulations have been approved or will be available soon: for subcutaneous weekly and monthly application, the depot formulations CAM 2038 (Buvidal®), the monthly depot formulation RBP-6000 (Sublocade™), and a 6-month buprenorphine implant (Probuphine™). Clinical data available so far on the efficacy of these 3 medications are given, and possible clinical implications are discussed.

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Optimal dose of buprenorphine in opioid use disorder treatment: a review of pharmacodynamic and efficacy data

Cited by 23 publications

References 56 publications

Associations of methadone and buprenorphine‐naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription‐type opioid use disorders: Exploratory analyses of the OPTIMA study

Associations of methadone and buprenorphine‐naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription‐type opioid use disorders: Exploratory analyses of the OPTIMA study

Lower buprenorphine elimination rate constant is associated with lower opioid use

Novel Long-Acting Buprenorphine Medications for Opioid Dependence: Current Update

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