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"Methadone - administration "
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Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial
2015
Methadone is an effective treatment for opioid dependence. When people who are receiving methadone maintenance treatment for opioid dependence are incarcerated in prison or jail, most US correctional facilities discontinue their methadone treatment, either gradually, or more often, abruptly. This discontinuation can cause uncomfortable symptoms of withdrawal and renders prisoners susceptible to relapse and overdose on release. We aimed to study the effect of forced withdrawal from methadone upon incarceration on individuals' risk behaviours and engagement with post-release treatment programmes.
In this randomised, open-label trial, we randomly assigned (1:1) inmates of the Rhode Island Department of Corrections (RI, USA) who were enrolled in a methadone maintenance-treatment programme in the community at the time of arrest and wanted to remain on methadone treatment during incarceration and on release, to either continuation of their methadone treatment or to usual care—forced tapered withdrawal from methadone. Participants could be included in the study only if their incarceration would be more than 1 week but less than 6 months. We did the random assignments with a computer-generated random permutation, and urn randomisation procedures to stratify participants by sex and race. Participants in the continued-methadone group were maintained on their methadone dose at the time of their incarceration (with dose adjustments as clinically indicated). Patients in the forced-withdrawal group followed the institution's standard withdrawal protocol of receiving methadone for 1 week at the dose at the time of their incarceration, then a tapered withdrawal regimen (for those on a starting dose >100 mg, the dose was reduced by 5 mg per day to 100 mg, then reduced by 3 mg per day to 0 mg; for those on a starting dose >100 mg, the dose was reduced by 3 mg per day to 0 mg). The main outcomes were engagement with a methadone maintenance-treatment clinic after release from incarceration and time to engagement with methadone maintenance treatment, by intention-to-treat and as-treated analyses, which we established in a follow-up interview with the participants at 1 month after their release from incarceration. Our study paid for 10 weeks of methadone treatment after release if participants needed financial help. This trial is registered with ClinicalTrials.gov, number NCT01874964.
Between June 14, 2011, and April 3, 2013, we randomly assigned 283 prisoners to our study, 142 to continued methadone treatment, and 141 to forced withdrawal from methadone. Of these, 60 were excluded because they did not fit the eligibility criteria, leaving 114 in the continued-methadone group and 109 in the forced-withdrawal group (usual care). Participants assigned to continued methadone were more than twice as likely than forced-withdrawal participants to return to a community methadone clinic within 1 month of release (106 [96%] of 110 in the continued-methadone group compared with 68 [78%] of 87 in the forced-withdrawal group; adjusted hazard ratio [HR] 2·04, 95% CI 1·48–2·80). We noted no differences in serious adverse events between groups. For the continued-methadone and forced-withdrawal groups, the number of deaths were one and zero, non-fatal overdoses were one and two, admissions to hospital were one and four; and emergency-room visits were 11 and 16, respectively.
Although our study had several limitations—eg, it only included participants incarcerated for fewer than 6 months, we showed that forced withdrawal from methadone on incarceration reduced the likelihood of prisoners re-engaging in methadone maintenance after their release. Continuation of methadone maintenance during incarceration could contribute to greater treatment engagement after release, which could in turn reduce the risk of death from overdose and risk behaviours.
National Institute on Drug Abuse and the Lifespan/Tufts/Brown Center for AIDS Research from the National Institutes of Health.
Journal Article
Diacetylmorphine versus Methadone for the Treatment of Opioid Addiction
by
Guh, Daphne
,
Brissette, Suzanne
,
Anis, Aslam
in
Addictive behaviors
,
Administration, Oral
,
Adult
2009
In this 12-month randomized trial involving 251 long-term heroin users, injectable diacetylmorphine (the active ingredient in heroin) was more effective than oral methadone in achieving retention in treatment for addiction and in reducing illicit-drug use and other illegal activity. As compared with methadone, injectable diacetylmorphine was associated with more serious adverse events, including seizures and drug overdoses.
In long-term heroin users, injectable diacetylmorphine (the active ingredient in heroin) was more effective than oral methadone in achieving retention in treatment for addiction and in reducing illicit-drug use and other illegal activity.
Opioid dependence, most commonly manifested as heroin dependence, is a chronic relapsing condition
1
that is estimated to affect more than 1 million persons in North America.
2
,
3
The risks of opioid dependence include fatal overdoses, infections (including endocarditis, human immunodeficiency virus infection, and hepatitis C virus infection), social disintegration, violence, and crime. The associated burdens on communities include medical, public health, and criminal-justice costs as well as public disorder and crimes against property.
Methadone, the standard opioid-substitution treatment, has been shown to reduce major risks associated with untreated opioid dependence in patients who are willing to undergo and are successfully . . .
Journal Article
Intravenous methadone for perioperative acute and chronic pain management in Chinese adult cardiac surgical patients: A protocol for pilot randomized controlled trial
by
Au, Sylvia Siu Wah
,
Wong, Wai Tat
,
Liu, Xiaodong
in
Acute Pain - drug therapy
,
Administration, Intravenous
,
Adult
2025
Postoperative pain is significant in cardiac surgical patients. Perioperative analgesia with intermittent administration of opioids can result in significant fluctuations in serum opioid concentrations. Methadone should provide a rapid onset and long-term pain relief upon a single intravenous dose at induction of anesthesia, and may reduce chronic postsurgical pain (CPSP) in cardiac surgical patients. The feasibility of using intravenous methadone in Chinese cardiac surgical patients, and its effect on acute and chronic pain management after cardiac surgery will be evaluated.
A single-center, prospective, randomized-controlled pilot trial. Adult cardiac surgical patients will be randomized to receive 0.2 mg/kg methadone or morphine at induction of anesthesia. Patient-controlled analgesia morphine protocol, oral paracetamol and dihydrocodeine will be given for postoperative analgesia. Venous blood sampling for plasma methadone concentration will be obtained at regular intervals from study drug infusion to 96 hours after administration. The primary outcome will be a description of study feasibility, encompassing recruitment and retention, protocol adherence and stakeholder acceptability. Secondary outcomes include the time of ventilator weaning to spontaneous breathing, time of extubation, morphine requirements within 24 hours and 72 hours after surgery, time to first morphine rescue, postoperative pain scores, patient satisfaction, and length of stay in ICU and hospital. Opioid-related side effects including sedation, nausea and vomiting, and time to first bowel opening will be recorded. CPSP will be assessed with Neuropathic Pain Scale and Pain Catastrophizing Scale at 3 and 6 months after surgery.
Randomized controlled trials on intravenous methadone in cardiac surgical patients are scarce, with none in Chinese populations. This study, supported by plasma methadone concentration analysis, will establish a basis for future large-scale research aimed at improving recovery through optimized pain management.
ClinicalTrials.gov NCT05913284.
Journal Article
Methadone versus other opioids for refractory malignant bone pain: a pilot randomised controlled study
2024
Purpose
Refractory cancer-induced bone pain (CIBP) affects a patient’s functional capacity and quality of life, but there is limited evidence to guide opioid choice. We assessed the feasibility, tolerability and possible efficacy of methadone rotation (MR) compared to other opioid rotations (OOR) in this cohort.
Methods
Adults with CIBP and worst pain intensity ≥ 4/10 and/or opioid toxicity graded ≥ 2 on the Common Terminology Criteria for Adverse Events were randomised 1:1 to methadone or another opioid rotation. Standardised assessment tools were used at pre-defined study time points up to 14 days.
Results
Of 51 eligible participants, 38 (74.5%) consented, and 29 (76.3%, MR: 14, OOR: 15) completed the fourteen days follow-up post-opioid rotation. Both groups displayed significant reduction in average (MR:
d
= − 1.2,
p
= 0.003, OOR:
d
= − 0.8,
p
= 0.015) and worst pain (MR:
d
= − 0.9,
p
= 0.042, OOR:
d
= − 0.6,
p
= 0.048) and total pain interference score (MR:
d
= − 1.1,
p
= 0.042, OOR:
d
= − 0.7,
p
= 0.007). Oral morphine equivalent daily dose was reduced significantly in MR compared to the OOR group (
d
= − 0.8,
p
= 0.05). The incidence of opioid-related adverse events following MR was unchanged but lower in the OOR group (
d
= 0.9, 95% CI 0.1,1.7,
p
= 0.022). There were no within-group or between-group differences in satisfaction with analgesia at the end of the study.
Conclusion
This pilot study demonstrated that MR and OOR in patients with refractory CIBP are feasible, safe and acceptable to patients. Appropriately powered multi-centre randomised controlled studies are needed to confirm the efficacy of MR and OOR in this cohort.
Trial registration
ACTRN12621000141842 registered 11 February 2021.
Journal Article
Assessing the comparative effectiveness of ECHO and coaching implementation strategies in a jail/provider MOUD implementation trial
by
Kim, Jee-Seon
,
Vechinski, Jessica
,
Tveit, Jessica
in
Adult
,
Buprenorphine
,
Buprenorphine - administration & dosage
2025
Background
For nearly two decades, it has been widely recognized that individuals in jail settings have a high prevalence of opioid use disorders (OUD) and are highly susceptible to fatal overdose upon their release. This setting provides a public health opportunity to address OUD with Medication for Opioid Use Disorders (MOUDs). Yet, 56% of jails do not provide MOUD, creating a pressing need for better implementation approaches in jail and the hand-off to the community. Two successful implementation strategies, NIATx external coaching and the Extension for Community Healthcare Outcomes (ECHO) case management telementoring model, were compared to address this persistent treatment gap.
Methods
This 2 × 2 design compared high (
n
= 12) and low (
n
= 4) dose coaching with and without ECHO in a 12-month intervention and 12 M sustainability period. The national trial included 25 jails and 13 community-based partners. MOUD trends for buprenorphine, methadone, injectable naltrexone, and combined MOUD between the study arms were assessed.
Results
Jail sizes ranged from 24% with < 100 and 24% with > 500 daily population, and community-based treatment providers ranged from 63% with < 50 and 7% with > 500 average monthly OUD intakes. New patient counts were found to significantly increase across the intervention phase for buprenorphine (
p
< .01) and combined MOUD (
p
< .01). Injectable naltrexone and methadone showed no consistent, significant gains. For sites with low coaching without ECHO, new patient counts for combined MOUD were predicted to increase by 47.44% during the intervention phase and 7.30% during the sustainability phase. ECHO demonstrated that MOUD use did not significantly increase compared to coaching across MOUDs in the intervention phase (
p
= .517). High- and low-dose coaching showed no significant differences in MOUD use during the intervention phase (
p
= .124).
Conclusions
Coaching emerged as a more effective implementation strategy than ECHO for increasing buprenorphine use in jail settings. In practice, ECHO sessions offered considerable overlap with coaching strategies. While high-dose coaching had greater gains for MOUDs overall than low-dose coaching, those gains were statistically insignificant, suggesting low-dose coaching to be more economical. To increase MOUD use in jail settings, jurisdictions should focus on new MOUDs so all three MOUDs are available and enhance the post-incarceration continuum of care.
Trial registration
Name of registry: ClinicalTrials.gov.
Trial registration number: NCT04363320.
Date of registration: 2020–07-30.
URL of trial registry record:
https://clinicaltrials.gov/study/NCT04363320?term=molfenter&rank=7
.
Journal Article
Perioperative methadone compared to placebo in elderly hip fracture patients: a study protocol for a randomized controlled trial (MetaHip trial)
by
Schønnemann, Jesper Ougaard
,
Nygaard, Kevin Heebøll
,
Petersen, Sofie Ronja
in
Addictions
,
Aged
,
Aged patients
2024
Background
Hip fractures are a source of severe pain among the elderly population and pose challenges due to limited analgesic tolerance. Perioperative methadone has shown promise in our pilot study suggesting a safe dose of 0.10 mg/kg, prompting further investigation into its benefits for elderly hip fracture patients.
Methods
This study employs a double-blinded randomized controlled trial to assess the analgesic effects of a single dose of methadone during hip fracture surgery. Patients aged ≥ 60 years are consecutively enrolled and randomized to receive either perioperative methadone (treatment group) or a saline solution (placebo group). A sample size of 130 patients is required for 88% statistical power. The medication is administered intravenously at anesthesia induction and monitored until discharge. A follow-up observation is conducted 3 months post-surgery.
Discussion
Primary outcome: Daily consumption of opioids within the first 3 days after surgery. Secondary outcomes include pain, mobility, nausea, vomiting, time to discharge, need for antidote, delirium, and constipation. The 3-month follow-up includes opioid use, pain, EQ-5D-5L scores, mobility, and persistent side effects. If statistically significant advantages are found in the treatment group, perioperative methadone could be considered as standard care for hip fracture patients, potentially enhancing their pain management. The study’s outcomes will provide insights into the feasibility and effectiveness of incorporating methadone into routine clinical practices for this patient group.
Trial registration
ClinicalTrials.gov ID: NCT06086171, submitted 4. October 2023. EU-CT: 2023–506252-24–00, UTN: U1111-1294–6125.
Journal Article
Effect of oral naloxone on opioid-induced constipation in methadone maintenance treatment patients, a double-blind, placebo-control, clinical trial
by
Vahdati-Mashhadian, Nasser
,
Etemad, Leila
,
Dadpour, Bita
in
Administration, Oral
,
Adult
,
Analgesics, Opioid - administration & dosage
2024
Background
Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC.
Method
Fifty-six MMT cases (< 75 mg/day methadone, > 3 months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4 mg/day) once a day for 2 weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks.
Results
The dose of 4 mg/day naloxone was excluded from the study due to severe OWS. The precipitants of groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2 mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (
P
= 0.0133), 0.5 mg/day dose only improved the stool consistency (
P
= 0.0016). The patients’ CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2 mg/day groups, respectively, withdrew from the study due to OWS.
Conclusion
Oral naloxone at doses of 0.5 and 2 mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4 mg induced intolerable OWS.
Journal Article
Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial
2017
Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain.
Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain.
We conducted a randomized, double blind, active-controlled parallel-group clinical trial.
Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period.
During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia.
Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms.
This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain.Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid.
Journal Article
Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial
by
Mayet, Soraya
,
Forzisi, Luciana
,
Martin, Anthea
in
Addictive behaviors
,
Administration, Oral
,
Adolescent
2010
Some heroin addicts persistently fail to benefit from conventional treatments. We aimed to compare the effectiveness of supervised injectable treatment with medicinal heroin (diamorphine or diacetylmorphine) or supervised injectable methadone versus optimised oral methadone for chronic heroin addiction.
In this multisite, open-label, randomised controlled trial, we enrolled chronic heroin addicts who were receiving conventional oral treatment (≥6 months), but continued to inject street heroin regularly (≥50% of days in preceding 3 months). Randomisation by minimisation was used to assign patients to receive supervised injectable methadone, supervised injectable heroin, or optimised oral methadone. Treatment was provided for 26 weeks in three supervised injecting clinics in England. Primary outcome was 50% or more of negative specimens for street heroin on weekly urinalysis during weeks 14–26. Primary analysis was by intention to treat; data were adjusted for centre, regular crack use at baseline, and treatment with optimised oral methadone at baseline. Percentages were calculated with Rubin's rules and were then used to estimate numbers of patients in the multiple imputed samples. This study is registered, ISRCTN01338071.
Of 301 patients screened, 127 were enrolled and randomly allocated to receive injectable methadone (n=42 patients), injectable heroin (n=43), or oral methadone (n=42); all patients were included in the primary analysis. At 26 weeks, 80% (n=101) patients remained in assigned treatment: 81% (n=34) on injectable methadone, 88% (n=38) on injectable heroin, and 69% (n=29) on oral methadone. Patients on injectable heroin were significantly more likely to have achieved the primary outcome (72% [n=31]) than were those on oral methadone (27% [n=11], OR 7·42, 95% CI 2·69–20·46, p<0·0001; adjusted: 66% [n=28]
vs 19% [n=8], 8·17, 2·88–23·16, p<0·0001), with number needed to treat of 2·17 (95% CI 1·60–3·97). For injectable methadone (39% [n=16]; adjusted: 30% [n=14]) versus oral methadone, the difference was not significant (OR 1·74, 95% CI 0·66–4·60, p=0·264; adjusted: 1·79, 0·67–4·82, p=0·249). For injectable heroin versus injectable methadone, a significant difference was recorded (4·26, 1·63–11·14, p=0·003; adjusted: 4·57, 1·71–12·19, p=0·002), but the study was not powered for this comparison. Differences were evident within the first 6 weeks of treatment.
Treatment with supervised injectable heroin leads to significantly lower use of street heroin than does supervised injectable methadone or optimised oral methadone. UK Government proposals should be rolled out to support the positive response that can be achieved with heroin maintenance treatment for previously unresponsive chronic heroin addicts.
Community Fund (Big Lottery) Research section, through Action on Addiction.
Journal Article
Cost-effectiveness of injectable opioid treatment v. oral methadone for chronic heroin addiction
2013
Despite evidence of the effectiveness of injectable opioid treatment compared with oral methadone for chronic heroin addiction, the additional cost of injectable treatment is considerable, and cost-effectiveness uncertain.
To compare the cost-effectiveness of supervised injectable heroin and injectable methadone with optimised oral methadone for chronic refractory heroin addiction.
Multisite, open-label, randomised controlled trial. Outcomes were assessed in terms of quality-adjusted life-years (QALYs). Economic perspective included health, social services and criminal justice resources.
Intervention costs over 26 weeks were significantly higher for injectable heroin (mean £8995 v. £4674 injectable methadone and £2596 oral methadone; P<0.0001). Costs overall were highest for oral methadone (mean £15 805 v. £13 410 injectable methadone and £10 945 injectable heroin; P = n.s.) due to higher costs of criminal activity. In cost-effectiveness analysis, oral methadone was dominated by injectable heroin and injectable methadone (more expensive and less effective). At willingness to pay of £30 000 per QALY, there is a higher probability of injectable methadone being more cost-effective (80%) than injectable heroin.
Injectable opioid treatments are more cost-effective than optimised oral methadone for chronic refractory heroin addiction. The choice between supervised injectable heroin and injectable methadone is less clear. There is currently evidence to suggest superior effectiveness of injectable heroin but at a cost that policy makers may find unacceptable. Future research should consider the use of decision analytic techniques to model expected costs and benefits of the treatments over the longer term.
Journal Article