Opioid agonist treatment for people who are dependent on pharmaceutical opioids

Nielsen, Suzanne; Tse, Wai Chung; Larance, Briony

doi:10.1002/14651858.cd011117.pub3

Cited by 14 publications

(10 citation statements)

References 170 publications

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“…We also excluded individuals who were on OAT in the last 4 weeks, had concomitant chronic pain necessitating some types of opioid therapy, or used heroin as the most frequent form of opioid in the last month. This last exclusion criterion was justified by the fact that patients primarily using heroin might differ from other patients with OUD in terms of the potency of the substances consumed, other comorbid physical and mental conditions, and associated risky behaviors 23,24 . More details are available elsewhere 2 .…”

Section: Methodsmentioning

confidence: 99%

“…This last exclusion criterion was justified by the fact that patients primarily using heroin might differ from other patients with OUD in terms of the potency of the substances consumed, other comorbid physical and mental conditions, and associated risky behaviors. 23,24 More details are available elsewhere. 2 For this specific secondary analysis, we excluded (n = 68) participants who did not initiate OAT after randomization or they only received treatments other than their assigned OAT at randomization.…”

Section: Participantsmentioning

confidence: 99%

See 1 more Smart Citation

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: Methodsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

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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“…Participants who used heroin as the most common drug of choice were excluded because they may have different clinical profiles in term of potency of opioid used and mental and physical comorbidities. 17,18 Individuals with an unstable mental or physical condition were excluded. The study included OPTIMA participants who received first OAT dose according to their assigned treatment at randomization and which was reported by pharmacy prescription abstraction (N = 167).…”

Section: Participantsmentioning

confidence: 99%

“…By excluding 12 participants from 1 site with potential false-positive UDS, methadone and BUP/NX dose titration ranges, durations, and rates were not associated with percentage of opioid-positive UDS (week 2-24). By using opioid-positive UDS in weeks 12-24, methadone and BUP/NX dose titration ranges and duration were not associated with percentage of opioidpositive UDS (week [12][13][14][15][16][17][18][19][20][21][22][23][24]. Methadone dose titration rate (ie, of dose adaptation) was negatively associated with percentage of opioid-positive UDS (week [12][13][14][15][16][17][18][19][20][21][22][23][24].…”

Section: Additional Analyses and Adjustments Of Associations Between ...mentioning

confidence: 99%

Associations of Methadone and BUP/NX Dose Titration Patterns With Retention in Treatment and Opioid Use in Individuals With Prescription-Type Opioid Use Disorder: Secondary Analysis of the OPTIMA Study

Bakouni,

Haquet,

Socias

et al. 2024

J Addict Med

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Introduction Methadone and buprenorphine/naloxone (BUP/NX) titration parameters (eg, range, duration, and rate) can vary during opioid use disorder (OUD) treatment. We describe methadone and BUP/NX titration patterns and their associations with treatment outcomes among individuals with a prescription-type OUD. Methods We used data from a 24-week open-label, multicenter randomized controlled trial, including N = 167 participants aged 18–64 years old with prescription-type OUD who received at least a first dose of treatment. Descriptive analyses of methadone and BUP/NX titration patterns were conducted, that is, range and duration from first to maximum dose, and rate (range/duration ratio). Outcomes included percentage of opioid-positive urine drug screens (UDS) and treatment retention. Adjusted linear and logistic regressions were used to study associations between titration patterns and percentage of opioid-positive UDS and treatment retention. Results Methadone doses were increased by a mean dose range of 42.4 mg over a mean duration of 42.2 days. BUP/NX doses were increased by a mean dose range of 8.4 mg over a mean duration of 28.7 days. Only methadone dose titration range (odds ratio: 1.03; 95% CI, 1.01 to 1.05) and duration (odds ratio: 1.03; 95% CI, 1.01 to 1.05) were associated with higher retention. Only methadone dose titration rate was associated with lower percentage of opioid-positive UDS at weeks 12–24 (B: −2.77; 95% CI, −4.72 to −0.81). Conclusions Specific parameters of methadone titration were associated with treatment outcomes and may help in personalizing treatment schedules. Sustained methadone dose titration, when indicated, may help increase retention, whereas faster dose titration for methadone may help decrease opioid use.

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“…Neuropathic pain is a growing global affliction affecting millions of people’s lives [ 1 ]. Alleviating neuropathic pain is challenging, as present clinical, widely used analgesics either have poor curative effects or are restricted by severe adverse effects [ 2 , 3 ]. There is thus a vast unmet need for the development of novel analgesics that effectively inhibit nociceptors without off-target effects on motor or central neurons.…”

Section: Introductionmentioning

confidence: 99%

Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Nav1.7 Voltage-Gated Sodium Channel

Yang

Shan

Guo

et al. 2022

IJMS

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Neuropathic pain is a refractory chronic disease affecting millions of people worldwide. Given that present painkillers have poor efficacy or severe side effects, developing novel analgesics is badly needed. The multiplex structure of active ingredients isolated from natural products provides a new source for phytochemical compound synthesis. Here, we identified a natural product, Narirutin, a flavonoid compound isolated from the Citrus unshiu, showing antinociceptive effects in rodent models of neuropathic pain. Using calcium imaging, whole-cell electrophysiology, western blotting, and immunofluorescence, we uncovered a molecular target for Narirutin’s antinociceptive actions. We found that Narirutin (i) inhibits Veratridine-triggered nociceptor activities in L4-L6 rat dorsal root ganglion (DRG) neurons, (ii) blocks voltage-gated sodium (NaV) channels subtype 1.7 in both small-diameter DRG nociceptive neurons and human embryonic kidney (HEK) 293 cell line, (iii) does not affect tetrodotoxin-resistant (TTX-R) NaV channels, and (iv) blunts the upregulation of Nav1.7 in calcitonin gene-related peptide (CGRP)-labeled DRG sensory neurons after spared nerve injury (SNI) surgery. Identifying Nav1.7 as a molecular target of Narirutin may further clarify the analgesic mechanism of natural flavonoid compounds and provide an optimal idea to produce novel selective and efficient analgesic drugs.

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Opioid agonist treatment for people who are dependent on pharmaceutical opioids

Cited by 14 publications

References 170 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

Associations of Methadone and BUP/NX Dose Titration Patterns With Retention in Treatment and Opioid Use in Individuals With Prescription-Type Opioid Use Disorder: Secondary Analysis of the OPTIMA Study

Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Nav1.7 Voltage-Gated Sodium Channel

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