Maintenance Treatment Of Opioid Dependence Research Articles

Evaluation of the Hepatotoxicity of Buprenorphine in Rat Pups Born to an Exposed Mother During Lactation.

This study aimed to evaluate the hepatotoxicity of buprenorphine in lactating rat pups of buprenorphine-injected mothers. Buprenorphine (BUP), a semisynthetic opioid, is increasingly administrated as a first-line standard maintenance treatment for opioid dependence due to its high safety and efficacy compared to other opioids. Numerous studies have confirmed the safety of BUP maintenance treatment in addicted patients. This study was designed to assess the effects of BUP on the activities of liver enzymes, oxidative parameters, and liver histopathological changes in pups born to a mother exposed to this drug during lactation. BUP at a dose of 0.5 or 0.1 mg/kg was subcutaneously administrated to lactating rats for 28 days. At the end of the experiment, the pups were anesthetized, and blood samples were obtained from their hearts for measuring liver enzymes. Then the livers of the animals were dissected to measure oxidative stress parameters. In addition, the liver samples were fixed for histopathological evaluation. The findings indicated a decrease in the activities of serum liver enzymes (ALT and AST) of the pups born to mothers exposed to 0.5 and 1 mg/kg of BUP during lactation. BUP could not change malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, nor superoxide dismutase (SOD) activity in the liver tissue of animals. Some vacuolated hepatocytes with dark, eccentric nuclei, necrosis with karyolytic nuclei, mitotic figures, and multiple binucleated cells were seen in the pups which received 1 mg/kg of BUP. In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.

A multicomponent LC-MS/MS method for drugs of abuse testing using volumetric DBS and a clinical evaluation by comparison with urine

BackgroundDrug testing commonly use urine as a specimen and immunoassays for screening. The need for supervised urine collection has led to an interest in alternative specimens and a need for using mass spectrometry methods already for screening. In addition, mass spectrometry methods allow for broad multipanel screening which of great value because of the increased number of substances that needs to be covered has increased over time. One alternative specimen of interest for drugs of abuse testing is dried blood spots (DBS) and this work aimed at developing multipanel screening methods based on selected reaction monitoring liquid chromatography - mass spectrometry for both urine and dried finger blood as specimens. Materials and MethodsThe urine method comprised 37 analytes and utilised salted out liquid/liquid extraction in 96-well format, respectively, and the blood method comprised 35 analytes, a 10 µL volumetric DBS device and a two-step solvent extraction procedure. In both cases stable isotope labelled internal standards were used for almost all analytes. ResultsThe methods were validated according to forensic standard. The lowest reporting limits were generally set at 100 ng/mL for urine and 1 ng/mL for blood and the accuracy and imprecision were within limits of 15 and 20%. The methods were applied in a clinical study on patients receiving methadone maintenance treatment for opioid dependence. Methadone was detected in all urine and DBS samples, for urine sometimes below the commonly applied screening cutoff limit of 300 ng/mL. In 20 out of 99 cases no other drug was detected in any specimen. The most commonly other detected substances were pregabalin, amphetamine, alprazolam, zopiclone and THCCOOH. Findings in urine and DBS generally agreed well but more positives were detected in DBS. ConclusionMultipanel methods using liquid chromatography – mass spectrometry suitable for clinical drug screening were successfully developed for urine and blood collected by finger-pricking and stored as DBS.

Deaddicta® for maintenance treatment of Opioid-dependence: A six-month follow-up.

Opioid dependence, is one of the world's most critical health problems. Deaddicta is a herbal product considered an effective treatment for opioid addiction. Deaddicta's efficacy in the maintenance treatment of patients with opioid use disorder has recently been demonstrated through a double-blind randomized controlled trial (RCT). This study aimed to evaluate the permanence of Deaddicta's efficacy six months after the end of the maintenance treatment for opioid dependence. This study was performed following the previous RCT on the maintenance treatment of opioid addicts. Out of 41 participants who completed the study for three months in the previous research, 15 from the intervention group (Deaddicta capsules, 1500 mg/day) returned for follow-up. They all previously fulfilled the DSM-IV criteria for addiction, were aged 18 to 65, and had discontinued Deaddicta for six months. The outcome measures included addiction severity, depression and anxiety levels, and craving score. The scores of each parameter were compared in three phases: before intervention; after three months of intervention; and six months after the end of the study. Depression, anxiety, and craving scores decreased six months after the end of the previous study. This decrease was significant in the craving score (P = 0.011). No significant increase was observed in the frequency of use. The regression analysis showed a negative relationship between craving and the progression of phases. The Deaddicta product may have desirable and effective properties in decreasing temptation and, as a result, the maintenance treatment of opioid dependence.

Comparing the Effects of Methadone, Buprenorphine, and Opium Tincture Maintenance Therapy on Sexual Function.

BackgroundOpioid use disorder is a major concern to public health, and opioid maintenance treatment on methadone or buprenorphine is a widely used approach. On the other hand, in recent years, there has been more regards for the use of opium tincture for detoxification and maintenance treatment of opioid dependence in certain parts of the world. The purpose of our research was to compare sexual impairments of methadone maintenance treatment (MMT), buprenorphine maintenance treatment (BMT), and opium tincture maintenance treatment (OMT) in patients.MethodsThe study sample consisted of opium-addicted men candidates for maintenance treatment in an addiction quitting clinic in Tehran, Iran, from November 2017 to February 2018. Participants (n = 84) were randomly assigned to three groups (of the equal number), receiving either methadone tablet, buprenorphine sublingual tablet, and opium tincture. The average score for sexual function was evaluated using the Arizona Sexual Experiences Scale (ASEX) at the beginning and after 3 months after treatment.FindingsAlthough there was no significant different in ASEX scores between the groups at the beginning and end of the study (P > 0.05), but the difference was significant in each group in comparing by themselves.ConclusionThese results showed that sexual dysfunction became better after opioid substitution therapies, and no differences were observed on sexual dysfunction between the three groups.

Transdermal buprenorphine patch: Potential for role in management of opioid dependence.

Despite proven clinical utility, use of sublinugual buprenorphine is fraught with issues of potential diversion among patients with opioid dependence. Transdermal buprenorphine patches provide an alternative delivery model that can be utilized to reduce such diversion. This narrative review discusses the transdermal buprenorphine formulations, and its pharmacology, drug interaction and tolerability profile. The studies utilizing buprenorphine transdermal patches in the treatment of opioid dependence are examined, while the potential of using such patches for maintenance treatment of opioid dependence is examined.

Can Tramadol be Used for Maintenance Treatment of Opioid Dependence?

Background: Certain limitations of the existing opioid substitution therapies necessitate exploration of other options for maintenance of patients with opioid dependence. This study aimed to present the experience of use of tramadol for long-term treatment of patients with opioid dependence. Methods: This was a cross-sectional interview-based observational study conducted in Uttar Pradesh state in India. Patients with opioid dependence who received oral tramadol treatment for a period of more than 6 months were recruited. Outcome was assessed in terms of self-reported abstinence on tramadol. Results: A total of 102 participants were recruited in the study, with a mean age of 41.3 years. All the participants were males. Abstinence to extraneous opioids was reported by 58.8% of the sample, and the median dose of tramadol at which abstinence was achieved was 350 mg/d. Those who reported to be taking natural opioids (raw opium or poppy husk) at the time of seeking treatment had higher rates of achieving abstinence. Conclusions: Tramadol may be a possible option for the maintenance treatment among some opioid-dependent individuals. Further studies are required to establish its efficacy vis-à-vis other medications used in opioid substitution treatment.

FDA approves new dosage strength of buprenorphine and naloxone sublingual film as maintenance treatment for opioid dependence

FDA approves new dosage strength of buprenorphine and naloxone sublingual film as maintenance treatment for opioid dependence

Methadone treatment, severe food insecurity, and HIV-HCV co-infection: A propensity score matching analysis

BackgroundSevere food insecurity (FI) is common among individuals living with HIV-hepatitis C virus (HCV) co-infection. We hypothesize that the injection of opioids is partly responsible for the association between injection drug use and severe FI. Therefore, this analysis examines whether methadone maintenance treatment for opioid dependence is associated with a lower risk of severe FI. MethodsWe used biannual data from the Canadian Co-infection Cohort (N = 608, 2012–2015). Methadone treatment (exposure) was self-reported and severe FI (outcome) was measured using the Household Food Security Survey Module. To quantify the association between methadone treatment and severe FI, we estimated an average treatment effect on the treated (marginal risk difference [RD]) using propensity score matching. ResultsAmong participants, 25% experienced severe FI in the six months preceding the first time-point in the analytical sample and 5% concurrently reported receiving methadone treatment. Injection of opioids in the six months preceding the treatment and outcome measurements was much higher among those who received methadone treatment (39% vs. 12%). Among the treated participants, 97% had injected opioids in their lifetimes. After propensity score matching, the average risk of experiencing severe FI is 12.3 percentage-points lower among those receiving methadone treatment, compared to those who are not receiving treatment (marginal RD = −0.123, 95% CI = −0.230, −0.015). ConclusionsAfter adjustment for socioeconomic, sociodemographic, behavioural, and clinical confounders, methadone treatment is associated with a lower risk of severe FI. This finding suggests that methadone treatment may mitigate severe FI in this vulnerable subset of the HIV-positive population.

Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment

BackgroundMethadone has been recognized as an effective maintenance treatment for opioid dependence. However, its use is associated with several complications, including sexual dysfunction in men. AimTo assess plasma testosterone and sexual function in Southeast Asian men on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT). Methods76 sexually active men on MMT (mean age = 43.30 ± 10.32 years) and 31 men on BMT (mean age = 41.87 ± 9.76 years) from a Southeast Asian community were evaluated using plasma total testosterone (TT) and prolactin levels, body mass index, social demographics, substance use measures, and depression severity scale. OutcomesPrevalence and associated factors of TT level lower than the reference range in men on MMT or BMT. ResultsMore than 1 third of men (40.8%, n = 31) on MMT had TT levels lower than the reference range, whereas 1 fourth of men (22.6%, n = 7) on BMT did. At univariate analysis, MMT vs BMT (β = 0.298, adjusted R2 = 0.08, P = .02) and body mass index (β = −0.23, adjusted R2 = 0.12, P = .02) were associated with changes in TT after stepwise regression. There were no significant associations with age; Opiate Treatment Index Q scores for alcohol, heroin, stimulant, tobacco, or cannabis use and social functioning domain; education levels; hepatitis C status; and severity of depression. Prolactin level did not differ between the MMT and BMT groups. Clinical ImplicationsThe sex hormonal assay should be used regularly to check men on MMT. Strengths and LimitationsThis is the first study conducted in the Southeast Asian community. Our study was limited by the lack of a healthy group as the reference for serum levels of testosterone and prolactin. ConclusionsThe findings showed that plasma testosterone levels are lower in MMT than in BMT users. Hence, men who are receiving MMT should be screened for hypogonadism routinely in the clinical setting.Yee A, Loh HS, Danaee M, et al. Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment. J Sex Med 2018;15:159–166.

Six-Year Outcome of Opioid Maintenance Treatment in Heroin-Dependent Patients: Results from a Naturalistic Study in a Nationally Representative Sample

Background: In many countries, the opioid agonists, buprenorphine and methadone, are licensed for maintenance treatment of opioid dependence. Many short-term studies have been performed, but little is known about long-term effects. Therefore, this study described over 6 years (1) mortality, retention and abstinence rates and (2) changes in concomitant drug use and somatic and mental health. Methods: A prevalence sample of n = 2,694 maintenance patients, recruited from a nationally representative sample of n = 223 substitution doctors, was evaluated in a 6-year prospective-longitudinal naturalistic study. At 72 months, n = 1,624 patients were assessed for outcome; 1,147 had full outcome data, 346 primary outcome data and 131 had died; 660 individuals were lost to follow-up. Results: The 6-year retention rate was 76.6%; the average mortality rate was 1.1%. During follow-up, 9.4% of patients became “abstinent” and 1.9% were referred for drug-free addiction treatment. Concomitant drug use decreased and somatic health status and social parameters improved. Conclusions: The study provides further evidence for the efficacy and safety of maintenance treatment with opioid agonists. In the long term, the number of opioid-free patients is low and most patients are more or less continuously under opioid maintenance therapy. Further implications are discussed.

Review highlights poor rates of patient retention in buprenorphine treatment

The Brown University Psychopharmacology UpdateVolume 28, Issue 4 p. 3-4 What's New in Research Review highlights poor rates of patient retention in buprenorphine treatment First published: 23 March 2017 https://doi.org/10.1002/pu.30221Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Although a number of studies have concluded that there is little benefit from adding a behavioral intervention to buprenorphine maintenance treatment for opioid dependence, a review of the research demonstrates ongoing limitations in the effectiveness of buprenorphine treatment as currently practiced, including a high dropout rate. The results indicate the need for more individualized treatment approaches for patients receiving buprenorphine, according to researchers. Volume28, Issue4April 2017Pages 3-4 RelatedInformation

Benzodiazepine, z-drug and pregabalin prescriptions and mortality among patients in opioid maintenance treatment—A nation-wide register-based open cohort study

BackgroundUse of sedatives may increase risk of death in opioid users. The aim of the study was to assess whether prescription of sedatives may be associated with mortality in patients in opioid maintenance treatment. MethodsThis retrospective register-based open cohort study included nation-wide register data including all individuals who were dispensed methadone or buprenorphine as opioid maintenance treatment for opioid dependence between July, 2005 and December, 2012 (N=4501). Outcome variables were overdose mortality and non-overdose mortality, respectively. Extended Cox regression analyses examined associations between type of sedative prescriptions and death, controlling for sex, age, previous overdoses and suicide attempts, psychiatric in-patient treatment and opioid maintenance treatment status. Opioid maintenance was assumed to last for 90days (or 30days in a sensitivity analysis) after the last methadone or buprenorphine prescription. ResultsBenzodiazepine prescriptions were associated with non-overdose death (HR: 2.02, 95% CI: 1.29–3.18) but not significantly associated with overdose death (1.49, 0.97–2.29). Z-drug (1.60, 1.07–2.39) and pregabalin prescriptions (2.82, 1.79–4.43) were associated with overdose death. In the sensitivity analysis, all categories of sedatives, including benzodiazepines, were significantly associated with overdose death. ConclusionsCaution is advised when prescribing sedative drugs, including benzodiazepines, z-drugs and pregabalin, to patients in opioid maintenance treatment.

Commentary on Nikoo et al. (2017): The role of research.

Opium tincture (OT) is used in Iran because it has two critical advantages—it is cheap, and it is less stigmatized than methadone. Stigma, and the problem of funding stigmatized treatments, is an issue in every country. Might OT be a solution? The evidence is limited, but reviewing it is useful. Nikoo and colleagues 1 report that in Iran there are 64 000 people in treatment with opium tincture (OT), the majority in slow withdrawal programmes. They have weighed the evidence concerning this preparation and found it wanting. They found observational trials of OT in substitution treatment, but no controlled trials. There were two controlled trials of OT in opioid withdrawal, with inconclusive results. Is OT a suitable medication for managing opioid dependence? Cost is one reason why the government of Iran used OT, and in low-income countries lower-cost treatment options are critical. Parsimony might seem a poor basis for choosing a medication without evidence to support it. However, absence of evidence of effectiveness is not evidence of absence of effectiveness. There are grounds for believing that almost any opioid can be used satisfactorily in substitution treatment 2. Well-controlled trials might reveal marginal differences in efficacy, but morphine, codeine and dihydrocodeine, to name a few opioids, have been used in observational studies 3, 4. OST medications do not even need to be long-acting or administered orally, as demonstrated by the effectiveness of injectable diamorphine and hydromorphone 5. Substitute medications work more effectively if they attenuate the effect of injected heroin—which is why high-dose methadone, inducing high opioid tolerance, is more effective than lower doses 6. As expected, a dose effect with OT was noted by Nikoo, with higher doses being more effective. In choosing between opioid drugs for substitution treatment, it might be a case of ‘anything goes’ (as long as given in sufficient dose); but in delivering medication to individuals, it is not the case that any approach is good enough. There are wide variations in how treatment is delivered 7—and better structured and supported treatment is more expensive to deliver and produces more effective outcomes 8. A more relevant question is whether slow opioid withdrawal a suitable treatment. Nikoo and colleagues comment that ‘we still do not have a satisfactory safe and effective treatment for detoxification and maintenance treatment of opioid dependence’; but spontaneous opioid withdrawal is not life-threatening. Most people dependent upon street opioids go through multiple episodes of withdrawal without formal treatment. On safety grounds, there is little need to offer detoxification—on the contrary, there is consistent evidence that post-detoxification heroin users are at increased risk of death 9. We can make withdrawal faster (rapid detoxification), or we can make it slower and less aversive, but however it is conducted relapse rates are high and risks of death post-withdrawal are increased 2, 10. The other major for using OT in Iran was the stigma against methadone. Stigma corrodes all aspects of substitution treatment. Stigma deters people from participating, and families pressure patients to avoid OST 11. People hate being on methadone, and drop out. Stigma against substitution treatment is one reason that professionals offer, and patients choose, detoxification rather than maintenance. The research reviewed by Nikoo and colleagues may permit few conclusions about OT relative to other medications, but it is important, none the less. Research helps to destigmatize treatment. It frames addiction as an empirical problem to be investigated, rather than an ethical problem to be corrected. It focuses not on the daily frustrations of dosing large numbers of people with minimal friction, but on the question of whether there are things we could do more effectively. It identifies end-points against which to evaluate treatment, guiding staff and patients towards realistic objectives and away from magical thinking. These ‘side effects’ of research into addiction are its greatest benefits—more valuable even than the occasional reporting of a vaguely relevant finding. Most of us have given up waiting for the big breakthrough that will cure addiction, but we still value the research enterprise. Research, even negative findings, helps us to think—and to cope with the stigma that bears down upon everyone involved in addiction. J.B. has received speaker's fees from Indivior and consultancy fees from Martindale Pharma.

Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method.

BackgroundBuprenorphine is a partial µ-opioid receptor agonist used for maintenance treatment of opioid dependence. Because of the partial agonism and high receptor affinity, it may precipitate withdrawal symptoms during induction in persons on full µ-opioid receptor agonists. Therefore, current guidelines and drug labels recommend leaving a sufficient time period since the last full agonist use, waiting for clear and objective withdrawal symptoms, and reducing pre-existing full agonist therapies before administering buprenorphine. However, even with these precautions, for many patients the induction of buprenorphine is a difficult experience, due to withdrawal symptoms. Furthermore, tapering of the full agonist bears the risk of relapse to illicit opioid use.CasesWe present two cases of successful initiation of buprenorphine treatment with the Bernese method, ie, gradual induction overlapping with full agonist use. The first patient began buprenorphine with overlapping street heroin use after repeatedly experiencing relapse, withdrawal, and trauma reactivation symptoms during conventional induction. The second patient was maintained on high doses of diacetylmorphine (ie, pharmaceutical heroin) and methadone during induction. Both patients tolerated the induction procedure well and reported only mild withdrawal symptoms.DiscussionOverlapping induction of buprenorphine maintenance treatment with full µ-opioid receptor agonist use is feasible and may be associated with better tolerability and acceptability in some patients compared to the conventional method of induction.

Pain and Opioid Addiction: A Systematic Review and Evaluation of Pain Measurement in Patients with Opioid Dependence on Methadone Maintenance Treatment.

While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These discrepancies may be a direct result of variations in the measurement of chronic pain or definitions of response to methadone treatment. The goal of this study is to evaluate the association between pain and substance use behaviour to determine the real impact of comorbid pain in the methadone population. We also aim to examine sources of variation across the literature with a specific focus on the measurement of pain. We performed a systematic review using an electronic search strategy across CINAHL, MEDLINE, Web of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane Reviews and the Cochrane Central Register of Controlled Trials databases. Title, abstract, as well as full text screening and extraction were performed in duplicate. Studies evaluating the association between chronic pain and methadone maintenance treatment response were eligible for inclusion in this review. Using a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA) research collaborative, we assessed the reliability of patient self-reported pain and the validated Brief Pain Inventory (BPI) assessment tool. After screening 826 articles we identified five studies eligible for full text extraction, of which three showed a significant relationship between the presence of pain and the increase in substance abuse among patients on methadone for the treatment of opioid dependence. Studies varied largely in the definitions and measurement of both pain and response to treatment. Results from our validation of pain measurement in the GENOA sample (n=297) showed the use of a simple self-reported pain question is highly correlated to the use of the BPI. Simply asking patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity, 84.4% PPV and 53.6% NPV to the BPI. The area under the ROC curve was 0.67 and the Pearson χ(2) was 37.3; (p<0.0001). The field of addiction medicine is at a lack of consensus as to the real effect of chronic pain on treatment response among opioid dependent patients. Whether it be the lack of a single "gold standard" measurement of response, or a lack of consistent measurement of pain, it is difficult to summarize and compare the results of these relatively small investigations. In comparison to the BPI, use of the simple self-reported pain has lower sensitivity for identifying patients with pain, suggesting the inconsistencies in these studies may result from differences in pain measurement. Future validation studies of pain measurement are required to address the predictive value of self-reported pain.

Effects of a Higher-bioavailability Buprenorphine/Naloxone Sublingual Tablet Versus Buprenorphine/Naloxone Film for the Treatment of Opioid Dependence During Induction and Stabilization: A Multicenter, Randomized Trial

PurposeSublingual buprenorphine and combination buprenorphine/naloxone (BNX) are effective options for the treatment of opioid dependence. A BNX sublingual tablet approved by the US Food and Drug Administration for the induction and maintenance treatment of opioid-dependence in adults was developed as a higher-bioavailability formulation, allowing for a 30% lesser dose of buprenorphine with bioequivalent systemic exposure compared with another BNX sublingual tablet formulation. No data were previously available comparing the higher-bioavailability BNX sublingual tablet to generic buprenorphine or BNX sublingual film; we therefore evaluated treatment retention during induction and stabilization with the higher-bioavailability BNX sublingual tablet versus generic buprenorphine or BNX sublingual film. MethodsThis multicenter, prospective, randomized, parallel-group noninferiority trial was conducted at 43 centers in the United States. Eligible patients were adults aged 18 to 65 years who met the criteria for opioid dependence and had at least mild withdrawal symptoms. On days 1 and 2, patients received blinded, fixed-dose induction with the higher-bioavailability BNX sublingual tablet or generic buprenorphine. On days 3 to 14, patients induced with BNX received open-label, titrated doses of the BNX tablet for stabilization; patients induced with buprenorphine received sublingual BNX film. Co-primary end points were treatment retention on days 3 and 15; noninferiority was concluded if the lower limit of the 95% CI of the between-group difference in treatment retention was ≥−10%. Tolerability was assessed throughout the study period. FindingsA total of 758 opioid-dependent patients were included in the study (BNX sublingual tablet, 383 patients; generic buprenorphine, 375). Day-3 retention rates were 93.9% (309/329) and 92.6% (302/326) with the BNX tablet and buprenorphine, respectively (between-group difference 95% CI, −2.6 to 5.1). Day-15 retention rates were 83.0% (273/329) and 82.5% (269/326) with the BNX tablet and BNX film, respectively (between-group difference 95% CI, –5.3 to 6.3). No unexpected tolerability issues were identified; the safety profile of the BNX sublingual tablet was similar to those of generic buprenorphine and BNX film. ImplicationsBased on the findings from this study in patients with opioid dependence, the higher-bioavailability BNX sublingual tablet formulation was noninferior to both generic buprenorphine (induction) and BNX film (stabilization). These findings suggest that BNX sublingual tablets are an efficacious and well-tolerated option for induction and early stabilization treatment of opioid dependence. ClinicalTrials.gov identifier: NCT01908842.

Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial

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.

Cost-Effectiveness of Injectable Extended-Release Naltrexone Compared With Methadone Maintenance and Buprenorphine Maintenance Treatment for Opioid Dependence

ABSTRACT. Background: The aim of this study was to estimate the cost-effectiveness of injectable extended-release naltrexone (XR-NTX) compared with methadone maintenance and buprenorphine maintenance treatment (MMT and BMT, respectively) for adult males enrolled in treatment for opioid dependence in the United States from the perspective of state-level addiction treatment payers. Methods: A Markov model with daily time cycles was used to estimate the incremental cost per opioid-free day in a simulated cohort of adult males aged 18–65 over a 6-month period from the state health program perspective. Results: XR-NTX is predicted to be more effective and more costly than methadone or buprenorphine in our target population, with an incremental cost per opioid-free day gained relative to the next-most effective treatment (MMT) of $72. The cost-effectiveness of XR-NTX relative to MMT was driven by its effectiveness in deterring opioid use while receiving treatment. Conclusions: XR-NTX is a cost-effective medication for treating opioid dependence if state addiction treatment payers are willing to pay at least $72 per opioid-free day.

Novel Buccal Film Formulation of Buprenorphine-Naloxone for the Maintenance Treatment of Opioid Dependence: A 12-Week Conversion Study

PurposeThe purpose of this study was to provide a preliminary assessment of the safety, tolerability, symptom control, and acceptability of buprenorphine-naloxone buccal film (BBN) for the maintenance treatment of opioid dependence in patients converted from buprenorphine-naloxone sublingual tablet or film (SLBN), as well as to determine the conversion ratio for switching patients from SLBN to BBN. MethodsThis open-label study included adult opioid-dependent subjects stabilized on 8/2 to 32/8 mg/d of SLBN for a minimum of 30 days. Study subjects were converted to a bioequivalent dose of BBN and maintained for 12 weeks. FindingsA total of 249 subjects (mean age 38.7 years, 65.9% male) were converted from SLBN to a single daily dose of BBN, and 79.1% completed the 12-week study. Adverse events and withdrawal symptoms led to discontinuation in 2.4% and 2.0% of BBN-treated subjects, respectively. Rates of constipation reported at baseline declined from 41% just before the initial BBN dose and within 24 hours of the last SLBN dose to 13% after 12 weeks of BBN treatment; treatment-emergent constipation was reported by 2.8% of BBN-treated subjects. Oral mucosal abnormalities were identified in 5% and 0.6% of systematic oral examinations in SLBN- and BBN-treated subjects, respectively. A total of 34 subjects had Clinical Opiate Withdrawal Scale total scores ranging from 10 to 25 (overall mean, 13.8) within 24 hours of taking their last SLBN dose, and scores for these subjects were reduced to a range of 0 to 3 (overall mean, 0.7) at 3 hours after the initial dose of BBN. Treatment compliance was high (108%); <1% of urine samples were buprenorphine-free, and 92.4% of BBN-treated subjects did not have a urine sample that tested positive for a non-prescribed opioid. A total of 91.3% subjects rated the taste of BBN as pleasant or neutral, and 82.5% rated BBN ease of use as easy or neutral. The overall mean final dose of BBN was 8.0/1.4 mg/d, yielding a 2:1 buprenorphine conversion ratio. ImplicationsAlthough these results should be considered preliminary due to the open-label design, BBN was overall safe and well tolerated, and seemed to provide adequate symptom control, in the treatment of opioid-dependent subjects previously controlled on SLBN for a minimum of 30 days. There was good adherence to study medication and favorable patient acceptance of the buccal formulation. The SLBN/BBN buprenorphine conversion ratio was 2:1. ClinicalTrials.gov identifier: NCT01666119.

Utilization and outcomes of detoxification and maintenance treatment for opioid dependence in publicly-funded facilities in California, USA: 1991–2012

BackgroundCalifornia treats the largest population of opioid dependent individuals in the USA and is among a small group of states that applies regulations for opioid treatment that are more stringent than existing federal regulations. We aim to characterize changes in patient characteristics and treatment utilization over time, and identify determinants of successful completion of detoxification and MMT retention in repeated attempts. MethodsState-wide administrative data was obtained from California Outcome Measurement System during the period: January 1st, 1991–March 31st, 2012. Short-term detoxification treatment and long-term maintenance treatment, primarily with methadone, was available to study participants. Mixed effects regression models were used to define determinants of successful completion of the detoxification treatment protocol (as classified by treatment staff) and duration of maintenance treatment. ResultsThe study sample consisted of 237,709 unique individuals and 885,971 treatment episodes; 837% were detoxification treatment episodes in 1994, dropping to 40.5% in 2010. Among individuals accessing only detoxification, the adjusted odds of success declined with each successive attempt (vs. 1st attempt: 2nd: OR: 0.679; 95% CI (0.610, 0.755); 3rd: 0.557 (0.484, 0.641); 4th: 0.526 (0.445, 0.622); 5th: 0.407 (0.334, 0.497); ≥6th: 0.339 (0.288, 0.399). For those ever accessing maintenance treatment, later subsequent attempts were longer in duration, and those with two or more prior attempts at detoxification had marginally longer subsequent maintenance episodes (hazard ratio: 0.97; 95% CI: 0.95, 0.99). Finally, only 10.9% of all detoxification episodes were followed by admission into maintenance treatment within 14 days. ConclusionsThis study has revealed high rates of detoxification treatment for opioid dependence in California throughout the study period, and decreasing odds of success in repeated attempts at detoxification.