ArticleLiterature Review

Maintenance Medication for Opiate Addiction: The Foundation of Recovery

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Abstract

Illicit use of opiates is the fastest growing substance use problem in the United States, and the main reason for seeking addiction treatment services for illicit drug use throughout the world. It is associated with significant morbidity and mortality related to human immunodeficiency virus, hepatitis C, and overdose. Treatment for opiate addiction requires long-term management. Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use. Similarly poor results are seen with medication-assisted detoxification. This article provides a topical review of the three medications approved by the Food and Drug Administration for long-term treatment of opiate dependence: the opioid-agonist methadone, the partial opioid-agonist buprenorphine, and the opioid-antagonist naltrexone. Basic mechanisms of action and treatment outcomes are described for each medication. Results indicate that maintenance medication provides the best opportunity for patients to achieve recovery from opiate addiction. Extensive literature and systematic reviews show that maintenance treatment with either methadone or buprenorphine is associated with retention in treatment, reduction in illicit opiate use, decreased craving, and improved social function. Oral naltrexone is ineffective in treating opiate addiction, but recent studies using extended-release naltrexone injections have shown promise. Although no direct comparisons between extended-release naltrexone injections and either methadone or buprenorphine exist, indirect comparison of retention shows inferior outcome compared with methadone and buprenorphine. Further work is needed to directly compare each medication and determine individual factors that can assist in medication selection. Until such time, selection of medication should be based on informed choice following a discussion of outcomes, risks, and benefits of each medication.

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... They are ideally started at the beginning of OWS and either kept at a low steady state or slowly tapered down over time. Methadone is a synthetic mu-opioid receptor agonist with a half-life of 28 h allowing for daily dosing [21]. Methadone reverses OWS by activating mu-opioid receptors, it decreases cravings for opioids and binds more avidly to the mureceptors than used opioids which decreases their euphoric effects. ...
... If a patient takes buprenorphine shortly after using an opioid it will induce OWS. For this reason, patients should not use any opioid 12-24 h before taking buprenorphine [21]. ...
... Naltrexone is a mu-opioid receptor antagonist. This medication works by blocking the euphoria of opioids by binding and blocking the mu-receptor with a higher affinity [21]. Some patients with OUD might have contraindications to the use of OAT. ...
Article
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The continued rise in the availability of illicit opioids and opioid-related deaths in the United States has left physicians, researchers, and lawmakers desperate for solutions to this ongoing epidemic. The research into therapeutic options for the treatment of opioid use disorder (OUD) began with the introduction of methadone in the 1960s. The approval of oral naltrexone initially showed much promise, as the drug was observed to be highly potent in antagonizing the effects of opioids while producing no opioid agonist effects of its own and having a favorable side effect profile. Patients that routinely take their naltrexone reported fewer days of heroin use and had more negative drug tests than those without treatment. Poor outcomes in OUD patients treated with naltrexone have been directly tied to short treatment time. Studies have shown that naltrexone given orally vs. as an implant at the 6-month interval showed a higher non-compliance rate among those who used oral medications at the 6-month mark and a slower return to use rate. There were concerns that naltrexone could possibly worsen negative symptoms seen in opiate use disorder related to blockade of endogenous opioids that are important for pleasurable stimuli. Studies have shown that naltrexone demonstrated no increase in levels of anxiety, depression and anhedonia in participants and another study found that those treated with naltrexone had a significant reduction in mental health-related hospitalizations. The latter study also concluded that there was no increased risk for mental health-related incidents in patients taking naltrexone via a long-acting implant. Although not yet FDA approved in the United States, naltrexone implant has shown promising results in Europe and Australia and may provide a novel treatment option for opioid addiction.
... Other experienced side effects in MMT are constipation, sweating, dry mouth, malaise, joint pain, reduced sexual desire, or a decreased ability to orgasm [14,15]. The tolerability of methadone can be limited in patients with prolongation of the electrocardiographic QTc interval [16,17], comedication of inhibitors/inducers of the cytochrome P450 enzymes [18,19], severe hepatic insufficiency [18], or rapid metabolizers [20,21]. The d-isomer does not bind to μ-receptors but demonstrates an effect on NMDA receptors that conceivably reduces the development of tolerance [22,23]. ...
... Other experienced side effects in MMT are constipation, sweating, dry mouth, malaise, joint pain, reduced sexual desire, or a decreased ability to orgasm [14,15]. The tolerability of methadone can be limited in patients with prolongation of the electrocardiographic QTc interval [16,17], comedication of inhibitors/inducers of the cytochrome P450 enzymes [18,19], severe hepatic insufficiency [18], or rapid metabolizers [20,21]. The d-isomer does not bind to μ-receptors but demonstrates an effect on NMDA receptors that conceivably reduces the development of tolerance [22,23]. ...
Article
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Purpose of Review This article aims to provide an overview of standard and adjunctive treatment options in opioid dependence in consideration of therapy-refractory courses. The relevance of oral opioid substitution treatment (OST) and measures of harm reduction as well as heroin-assisted therapies are discussed alongside non-pharmacological approaches. Recent Findings Currently, recommendation can be given for OST with methadone, buprenorphine, slow-release oral morphine (SROM), and levomethadone. Heroin-assisted treatment using diamorphine shall be considered as a cost-effective alternative for individuals not responding to the afore-mentioned opioid agonists in order to increase retention and reduce illicit opioid use. The modalities of application and the additional benefits of long-acting formulations of buprenorphine should be sufficiently transferred to clinicians and the eligible patients; simultaneously methods to improve planning of actions and self- management need to be refined. Regarding common primary outcomes in research on opioid treatment, evidence of the effectiveness of adjunctive psychological interventions is scarce. Summary Maintaining a harm reduction approach in the treatment of opioid addiction, a larger range of formulations is available for the prescribers. Embedding the pharmacological, ideally individualized treatment into a holistic, structure-giving concept also requires a reduction of fragmentation of ancillary services available, drug policies, and treatment philosophies on a global scale.
... Unsurprisingly, in terms of sheer quantity, most drug poisoning deaths (75%) occur among white people of low socioeconomic status living in urban areas, given the much larger populations in those areas (Larney and Hall, 2019). However, the epidemic is accelerating rapidly among African American adults-between 2009-2018 the age-adjusted death rate due to opioid involved overdose has increased by 289% among African American adults (Goedel et al., 2020) Additional complications stem from the incidence of blood borne viruses such as HIV, hepatitis B and hepatitis C being higher in illicit opioid users than in the general population (Bart, 2012). The efficacy of opioid-restrictive supply-side policies are limited when not complemented with demand side strategies focused on factors motivating the misuse of drugs and concerted efforts to engage persons with OUD in a comprehensive cascade of evidence-based treatment (Alpert et al., 2017;Bohnert and Ilgen, 2019). ...
... Research suggests that the use of medication combined with behavioral counseling can be an effective treatment regime for opioid dependence (Nielsen et al., 2016). While other substance use disorders may achieve remission without the use of medication-assisted treatment (MAT), also known as Medication for Opioid Use Disorder (MOUD) in the context of OUD, behavioral interventions relying on self-compelled abstinence of opioid use have extremely poor outcomes, with relapse occurring in more than 80% of cases (Bart, 2012). MOUD with FDA-approved methadone or buprenorphine has been shown to increase treatment retention, to reduce opioid use and associated health and societal harms, and opioid related overdose, and as such is considered the most effective treatment for OUD (Beletsky and Davis, 2017; C. M. Jones et al., 2015). ...
Article
Drug overdose is the leading cause of accidental death in the U.S. with deaths from opioid overdose occurring at a higher rate in rural areas. The gaps in the provision of healthcare services have been exacerbated by the opioid crisis leaving vulnerable populations without access to preventative care and education, harm reduction, both chronic and acute treatment of the symptoms of opioid use disorder (OUD), and long-term psychological support for those with OUD and their families. There has been a call in the literature -and a federal mandate-for increased access to opioid treatment facilities, but to date this access has not been operationalized using best practices in geography. Medication for Opioid Use Disorder (MOUD) with FDA-approved methadone or buprenorphine has been shown to increase treatment retention, reduce opioid use and associated health and societal harms, and reduce opioid related overdose, and as such is considered the most effective treatment for OUD. The objective of this study is to examine U.S. adults' spatial access to MOUD — specifically locations of certified Opioid Treatment Programs (OTPs) and DATA-waived Buprenorphine providers. A gravity-based variant of the enhanced two-step floating catchment area model is employed, where friction of distance is based on previously published willingness to travel distances for patients visiting OTPs, to assess how opioid agonist treatment accessibility varies across the nation. Findings suggest that there are extensive ‘treatment deserts’ where there is little to no physical access to MOUD, especially in rural areas. The significance of this work lies in the incorporation of treatment utilization behavior in the access metric, and the continued confirmation of gaps in access to OUD services despite federal efforts to improve accessibility.
... 5−7 Methadone, buprenorphine, and naltrexone ( Figure 1) are first-line opioid medicines approved by the US Food and Drug Administration (FDA) for opioid use disorders. 5 Methadone and buprenorphine, μ opioid receptor (MOR) full and partial agonists, respectively, show good efficacy for opioid addiction maintenance therapy. 8−10 However, about 50% of patients relapse after being treated for opioid use disorders with methadone and buprenorphine. ...
... After being concentrated, the residue was purified by flash column chromatography with CH 2 Cl 2 /MeOH (1% NH 3 ·H 2 O) as the eluent to give the free base. 38 After structural confirmation by 1 H NMR, the corresponding free base was then converted into a hydrochloride salt, which was fully characterized by 1 H NMR, 13 13 (5). Compound 5 was synthesized as shown in the general procedure with 72% yield. 1 13 17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(3′pyrrolyl)acetamido]morphinan Hydrochloride (10). ...
... Opioid agonists suppress craving and withdrawal symptoms related to OUD, and block the effects of other opioids. 10 Opioid agonists include methadone and buprenorphine. 10 Stakeholders are particularly interested in models of care considered to be low-threshold (e.g., do not require ongoing counseling to receive treatment). 5. What health service delivery models are available to treat these patients (e.g., health homes, housing first, "low-threshold" treatment programs), and how are these models structured and implemented? ...
... 10 Opioid agonists include methadone and buprenorphine. 10 Stakeholders are particularly interested in models of care considered to be low-threshold (e.g., do not require ongoing counseling to receive treatment). 5. What health service delivery models are available to treat these patients (e.g., health homes, housing first, "low-threshold" treatment programs), and how are these models structured and implemented? ...
Research
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This 2019 systematic review assesses the evidence for the effectiveness of behavioral health interventions as part of a medication-assisted treatment (MAT) regimen for opioid use disorder (OUD). The report also evaluates clinical practice guideline recommendations for behavioral health treatments as a part of MAT and describes 3 service delivery models that implement low-threshold MAT programs in Missouri, Virginia and in the Veterans Health Administration.
... Methadone and buprenorphine are both opioids, acting fully and partially on mu-opioid receptor, respectively (Kleber, 2007). Methadone and buprenorphine have been approved by the FDA in opioid replacement therapy (Bart, 2012). Methadone safety is well documented and proven (Kreek, 1973). ...
... Methadone safety is well documented and proven (Kreek, 1973). However, if taken beyond the tolerance of the person, methadone could cause respiratory depression (Bart, 2012). The respiratory depression could also be fatal in the event of overdose since there is no ceiling level to it (Mattick et al., 2008). ...
Article
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Background: Kratom or Mitragyna speciosa Korth has been widely used to relieve the severity of opioid withdrawal in natural settings. However, several studies have reported that kratom may by itself cause dependence following chronic consumption. Yet, there is currently no formal treatment for kratom dependence. Mitragynine, is the major psychoactive alkaloid in kratom. Chronic mitragynine treatment can cause addiction-like symptoms in rodent models including withdrawal behaviour. In this study we assessed whether the prescription drugs, methadone, buprenorphine and clonidine, could mitigate mitragynine withdrawal effects. In order to assess treatment safety, we also evaluated hematological, biochemical and histopathological treatment effects. Methods: We induced mitragynine withdrawal behaviour in a chronic treatment paradigm in rats. Methadone (1.0 mg/kg), buprenorphine (0.8 mg/kg) and clonidine (0.1 mg/kg) were i.p. administered over four days during mitragynine withdrawal. These treatments were stopped and withdrawal sign assessment continued. Thereafter, toxicological profiles of the treatments were evaluated in the blood and in organs. Results: Chronic mitragynine treatment caused significant withdrawal behaviour lasting at least 5 days. Methadone, buprenorphine, as well as clonidine treatments significantly attenuated these withdrawal signs. No major effects on blood or organ toxicity were observed. Conclusion: These data suggest that the already available prescription medications methadone, buprenorphine, and clonidine are capable to alleviate mitragynine withdrawal signs rats. This may suggest them as treatment options also for problematic mitragynine/kratom use in humans.
... Studies have shown that suboxone MAT programs can be more effective, with respect to drug adherence, than other types of OUD treatments, such as methadone, tramadol or naltrexone, in part due to lower incidences of adverse drug reactions and side effects [9][10][11][12]. ...
Article
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Background: Suboxone (buprenorphine-naloxone combination drug) is prescribed for opioid use disorders (OUD) treatment. Naloxone (in suboxone) acts an antagonist to dissuade drug overdose. Medication compliance is key to OUD treatment. While there are several methodologies to assess compliance for buprenorphine, little has been studied regarding naloxone compliance monitoring issues. Our study sheds more light into the role of naloxone and nor-naloxone in suboxone compliance monitoring and emphasizes the value of combined analysis of urine buprenorphine, norbuprenorphine, naloxone, and nor-naloxone, in medication compliance of OUD patients in suboxone medication-assisted treatment (MAT).
... 10 When agonist medications are used for long-term treatment, complete detoxification is not required as patients simply transition from illicit use into opioid agonist therapy without having to suffer withdrawal. 11 When MOUD are used for pharmacologically assisted withdrawal, patients achieve complete detoxification by tapering gradually with the assistance of an opioid agonist or other supportive medication to mitigate withdrawal symptoms. 12 While both of these methods are still widely used, evidence has shown that long-term treatment with methadone or buprenorphine is more effective than tapering and detoxification (i.e., pharmacologically assisted withdrawal). ...
Article
Background: Research has shown that medications, especially opioid agonist treatments, are an effective way to treat opioid use disorder (OUD); however, negative attitudes held by health professionals contribute to their underutilization. Methods: A 23-year review of studies that examined health professionals’ attitudes toward medications for OUD (MOUD) was conducted to describe the current state of knowledge and to inform future research and interventions. Results: Studies examined attitudes toward the use of methadone, buprenorphine, and naltrexone among various types of health professionals: prescribers, non-prescribing clinicians, pharmacists, and administrators. The characteristics and findings of the included studies were reviewed and synthesized. Findings indicate that attitudes toward MOUD affect access and utilization by influencing prescribing practices, referrals, and adoption within programs. Exposure, knowledge, and treatment orientation were found to be important factors related to attitudes toward MOUD across multiple studies of various types of health professionals. Conclusions: To increase access and utilization, continued efforts are needed to increase positive attitudes toward MOUD among various types of health professionals. Findings indicate that interventions should seek to increase knowledge about MOUD and foster interprofessional communication related to MOUD, especially between prescribers and behavioral health providers.
... The most widely prescribed treatment for opioid dependence is long-term opioid agonist treatment (OAT), usually with oral methadone, sublingual buprenorphine, or slow-release oral morphine (Bart, 2012;Kraigher et al., 2005). However, some patients do not benefit from these interventions (Fairbairn et al., 2019;Mattick et al., 2009;Morral et al., 1999;Strang et al., 2012). ...
Article
Objective To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence. Methods The PubMed, Embase, Web of Science and PsycINFO databases were searched. Eleven published studies were identified and selected based on defined eligibility and exclusion criteria. Results Four pharmacokinetic studies reported negligible plasma concentrations of diacetylmorphine and its active metabolite 6-monacetylmorphine. Among six pharmacodynamic studies, three trials showed that oral diacetylmorphine reduced opioid withdrawal symptoms, one open-label pilot study reported that two patients experienced a modest ‘rush’ after oral diacetylmorphine and two studies found that patients could not distinguish between oral diacetylmorphine, methadone, or morphine. Regarding the clinical studies, a Swiss prospective cohort study in patients with heroin dependence showed high retention rates of oral diacetylmorphine treatment with few serious adverse events, whereas in the Canadian SALOME trial, oral diacetylmorphine treatment was prematurely discontinued because treatment retention of oral diacetylmorphine was lower than injectable diacetylmorphine maintenance treatment. Finally, two case studies illustrate the limitations and potential problems of oral diacetylmorphine in the treatment of treatment-refractory heroin dependent patients. Conclusions Based on all published data, it is unlikely that oral diacetylmorphine produces a substantial ‘rush’. Prescription of oral diacetylmorphine might therefore be effective only for treatment-refractory patients with heroin dependence (i) as maintenance treatment for those who never injected or inhaled opioids; (ii) as maintenance treatment for those who want to switch from injection to oral administration of diacetylmorphine; and/or (iii) to reduce opioid withdrawal symptoms.
... Currently, opioid use disorder (OUD), involving both prescription opioid medications and illicit opioids, is a public health crisis in the USA, having reached epidemic proportions in the past several years. 1 A recent national survey estimates that at least 2.5 million people in the USA have OUD. 2 Previous models of OUD treatment, primarily focused on psychosocial counseling and behavioral treatments, have been strengthened by the addition of pharmacological therapies in association with these psychosocial treatments; this was formerly referred to as medication-assisted treatment (MAT) and is now known as medication treatment of OUD (MOUD). 3 MOUD has been studied at length, and there is strong evidence demonstrating improved outcomes, increased retention in treatment, and decreased morbidity and mortality in the OUD population treated with this therapy. 4 Given these benefits, expansion of access to MOUD critically decreases morbidity and mortality from OUD and associated medical problems, 5 with positive downstream effects on healthcare resources and society. ...
Article
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Background The past two decades have witnessed an epidemic of opioid use disorder (OUD) in the USA, resulting in catastrophic loss of life secondary to opioid overdoses. Medication treatment of opioid use disorder (MOUD) is effective, yet barriers to care continue to result in a large proportion of untreated individuals. Optimal analgesia can be obtained in patients with MOUD within the perioperative period. Anesthesiologists and pain physicians can recommend and consider initiating MOUD in patients with suspected OUD at the point of care; this can serve as a bridge to comprehensive treatment and ultimately save lives. Methods The Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, American Society of Anesthesiologists, American Academy of Pain Medicine, American Society of Addiction Medicine and American Society of Health System Pharmacists approved the creation of a Multisociety Working Group on Opioid Use Disorder, representing the fields of pain medicine, addiction, and pharmacy health sciences. An extensive literature search was performed by members of the working group. Multiple study types were included and reviewed for quality. A modified Delphi process was used to assess the literature and expert opinion for each topic, with 100% consensus being achieved on the statements and each recommendation. The consensus statements were then graded by the committee members using the United States Preventive Services Task Force grading of evidence guidelines. In addition to the consensus recommendations, a narrative overview of buprenorphine, including pharmacology and legal statutes, was performed. Results Two core topics were identified for the development of recommendations with >75% consensus as the goal for consensus; however, the working group achieved 100% consensus on both topics. Specific topics included (1) providing recommendations to aid physicians in the management of patients receiving buprenorphine for MOUD in the perioperative setting and (2) providing recommendations to aid physicians in the initiation of buprenorphine in patients with suspected OUD in the perioperative setting. Conclusions To decrease the risk of OUD recurrence, buprenorphine should not be routinely discontinued in the perioperative setting. Buprenorphine can be initiated in untreated patients with OUD and acute pain in the perioperative setting to decrease the risk of opioid recurrence and death from overdose.
... Yet the transition period, also called induction phase, is a critical point of time in the detoxification of substance use. During this phase, withdrawal from treatment, side effects from detoxification, and lack of engagement are common barriers due to the intense process (Bart, 2012;Marsch, 1998), leading to potential disengagement. However, nonpharmacologic implementation to assist in the transition phase could provide alternative methods to reduce the withdrawal effects. ...
Article
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Background Medication-assisted treatment can reduce mortality and withdrawal symptoms, yet treatments can have side effects and are cost ineffective. Research has supported alternative approaches to withdrawal symptoms, specifically percutaneous nerve field stimulator (PNFS); yet, to date, there is a lack of understanding of the initial acceptability within treatment programs. Methods A retrospective case series evaluated PNFS to reduce opioid withdrawal symptoms for five adult patients participating in an in-home withdrawal management program. The device was worn for five consecutive days, in which a licensed practical nurses monitored their care. Evaluation included the clinical opiate withdrawal scale (COWS) and clinical reviews based on self-report and clinician interview. Results Significant reductions were noted for all five participants, with the average COWS score for Day 1 at 19.1 reducing to 2.6 at Day 5. In addition, 2-day post-COWS scores demonstrated a continual reduction to 1.4. Qualitative feedback from the patients was recorded, and generalized themes were recorded and addressed. Conclusions Future controlled, prospective studies should investigate the possibility that PNFS can significantly reduce negative symptoms of opiate withdrawal symptoms, along with providing alternatives to medication-assisted treatments for those who are suffering from opiate use disorder.
... Opioid substitution therapy (OST) with methadone maintenance treatment (MMT) is the most promising harm reduction intervention for reducing illicit opioid use [3]. Although MMT is shown to curtail HIV spread and improve health, it is also equally important to evaluate clients social functioning in the MMT program [4]. A systematic review and meta-analysis of methadone treatment report a decrease in the self-reported arrest rate, clients' drug selling rate, rates of selling sex for drugs and drug-related crime from the baseline to 6 month and 12 months of intervention. ...
Article
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Background: Opioid substitution with methadone maintenance treatment (MMT) is shown to reduce illicit opioid use and renew social functioning. Understanding factors that undermine clients' social functioning during MMT treatment is vital for improving treatment compliance and quality of life. Method: A total of 210 respondents who were already enrolled in a formal MMT program in Myanmar were recruited from five cities through stratified random sampling for this cross-sectional study. The addiction severity index (ASI) was used to objectively assess respondents social functioning in the last 30 days. Higher ASI scores denote poorer social functioning. Result: Respondents total ASI scores in the respective domains were: employment (47.4%), alcohol (44.4%), drug use (7.2%), legal (49.2%) and social-family relationship (10.7%). Those reported to have never injected drugs in the last 30 days had lower ASI total scores than those who reported injection drug use (p = 0.01). After identifying the differences in ASI total scores, we found there were significant associations in the clients' hepatitis C status, age category, frequency of heroin injection, quality of life score, marital status, current leisure status with family/friend, current history of injection in the last 30 days, income status, satisfaction with current marital status, as well as reported drug and alcohol use (p < 0.05). Stepwise binary logistic regression showed that alcohol and higher frequency of heroin injection were associated with higher ASI scores. Meanwhile, older age, respondents those who had leisure time with family, and satisfied with current marital status had lower ASI scores (p < 0.05). Conclusion: Our results indicate that those enrolled in the MMT program in Myanmar faced many challenges in their daily social functioning. Treatment providers must take heed of these apparent impediment to ensure clients chequered social functioning does not undermine their treatment compliance. Trial registration: NA.
... Understanding discontinuation of treatment is important to support recovery, as retention in OUD treatment is one of the factors most consistently associated with favorable outcomes (Bart, 2012). Conversely, research has shown early discontinuation of OMT to be associated with increased risk of relapse and mortality (Clausen et al., 2008;Cousins et al., 2011;Kornor & Waal, 2005;Krawczyk et al., 2020;Williams et al., 2020). ...
Article
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Background Extended-release naltrexone (XR-NTX), an opioid antagonist, has demonstrated equal treatment outcomes, in terms of safety, opioid use, and retention, to the recommended OMT medication buprenorphine. However, premature discontinuation of XR-NTX treatment is still common and poorly understood. Research on patient experiences of XR-NTX treatment is limited. We sought to explore participants' experiences with discontinuation of treatment with XR-NTX, particularly motivation for XR-NTX, experiences of initiation and treatment, and rationale for leaving treatment. Methods We conducted qualitative, semi-structured interviews with participants from a clinical trial of XR-NTX. The study participants (N = 13) included seven women and six men with opioid dependence, who had received a minimum of one and maximum of four injections of XR-NTX. The study team analyzed transcribed interviews, employing thematic analysis with a critical realist approach. Findings The research team identified three themes, and we present them as a chronological narrative: theme 1: Entering treatment – I thought I knew what I was going into; theme 2: Life with XR-NTX – I had something in me that I didn't want; and theme 3: Leaving treatment – I want to go somewhere in life. Patients' unfulfilled expectations of how XR-NTX would lead to a better life were central to decisions about discontinuation, including unexpected physical, emotional, or mental reactions as well as a lack of expected effects, notably some described an opioid effect from buprenorphine. A few participants ended treatment because they had reached their treatment goal, but most expressed disappointment about not achieving this goal. Some also expressed renewed acceptance of OMT. The participants' motivation for abstinence from illegal substances generally remained. Conclusion Our findings emphasize that a dynamic understanding of discontinuation of treatment is necessary to achieve a long-term approach to recovery: the field should understand discontinuation as a feature of typical treatment trajectories, and discontinuation can be followed by re-initiation of treatment.
... This change to telehealth delivery may significantly impact buprenorphine availability. Retention in MOUD treatment is associated with decreased drug use, improved social functioning and quality of life, and reduced mortality (Bart, 2012;Fullerton et al., 2014;Stotts, Dodrill, & Kosten, 2009); adding to the importance of continued access to MOUD treatment, despite the change in delivery of the program. ...
Article
Introduction This study evaluates if social distancing measures instituted during the novel coronavirus SARS-CoV-2 (COVID-19) pandemic were associated with a reduction in Medication for Opioid Use Disorder (MOUD) prescribing in West Virginia. The COVID-19 pandemic necessitated the quick implementation of public health interventions such as social distancing. This led to the use of telemedicine in the clinical setting however implementing telemedicine involves system level and infrastructure level changes within a healthcare environment. This could cause a barrier to MOUD delivery as it is often provided concomitantly with other face to face substance use and mental health services. The purpose of this study is to determine whether social distancing was associated with a reduction in MOUD prescribing in West Virginia, with the goal of adding to the knowledge of how COVID-19 and COVID-19-related mitigation strategies have impacted patients with OUD. Methods Prescription monitoring data were requested from the West Virginia Board of Pharmacy. We applied interrupted time series modeling to investigate MOUD prescribing practices before and after social distancing took effect. Gabapentin prescriptions were utilized as a control for comparison. Results Our study assessed state-wide buprenorphine and Suboxone prescriptions as compared to a control medication and found an increase in dosage of both medications and an increase in number of buprenorphine prescriptions, but a small decrease in buprenorphine/naloxone prescription number related to the dates of implementation of social distancing. Taken together, overall this indicates an increase in prescription number of MOUD prescriptions as well as an increase in dosage. Conclusion This study suggests that social distancing measures were associated with an increase in both the number of MOUD prescriptions and the number of doses in each prescription. Significant alterations to MOUD delivery in the clinical setting were implemented in a short timeframe with the COVID-19 pandemic. Understanding the implementation of clinical measures to accommodate social distancing measures may provide benefit to transformation of future delivery of MOUD.
... Extensive research has shown that medication-assisted treatment is superior in treatment outcomes to non-medication-based therapies in reducing opioid use, overdoses and overdose deaths, and improving social functions and quality of life. 16 In a study of 699 adults randomized to either methadone or buprenorphine/naloxone and followed for at least 5 years, only 20.7% of them were abstinent from heroin and other opioids during the preceding 5 year period. 17 Relapse rates were high. ...
Article
The opioid crisis has devastated the U.S. more than any other country, and the epidemic is getting worse. While opioid prescriptions have decreased by more than 40% from its peak in 2010, unfortunately, opioid-related overdose deaths have not declined but continued to increase. With greater scrutiny on prescription opioids, many users switched to the cheaper and more readily available heroin that drove up heroin-related overdose deaths from 2010 to peak in 2016, being overtaken by the spike in synthetic opioid (mostly fentanyl)-related overdose deaths. The surge in fentanyl-related overdose deaths since 2013 is alarming as fentanyl is more potent and deadly. One thing is certain the opioid crisis is not improving but has become dire with the surge in fentanyl-related overdose deaths. Evidence-based strategies have to be implemented in the U.S. to control this epidemic before it destroys more lives. Other countries, including European countries and Canada, have invested more in harm reduction strategies than the U.S. even though they (especially Europe) do not face anywhere near the level of crisis as the U.S. In the long-run, upstream measures (tackling the social determinants of health) are more effective public health strategies to control the epidemic. In the meantime, however, harm reduction strategies have to be employed to mitigate the harm from addiction and overdose deaths.
... At the population level, the most concerned substances are tobacco, cannabis and alcohol use. Among former substance users, prevention of relapse is also a major issue 10 . Sugar and fat overconsumption are also highly prevalent in western countries and they share common vulnerability factors with substance use 9 . ...
Preprint
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We examined the prospective association of physical exertion at work with subsequent tobacco, cannabis, alcohol use, and sugar and fat consumption. Volunteers of the French population-based CONSTANCES cohort currently employed were included from 2012–2017 for tobacco and cannabis outcomes (n = 100,612), and from 2012–2016 for alcohol and sugar and fat outcomes (n = 75,414). High level of physical exertion at work was defined as a score ≥ 12 at the Rating Perceived Exertion Borg scale. Substance use was self-reported and diet rich in sugar and fat was obtained from principal component analysis and analyzed as quartiles. Generalized linear models computed odds of substance use and sugar and fat consumption at follow-up according to baseline physical exertion at work, while adjusting for sociodemographic factors, depressive symptoms and baseline level of consumption. High physical exertion was associated with tobacco use with dose-dependent relationships. It was also associated with increased odds of cannabis use at least once per month compared to no use in the past and with increased odds of diet rich in sugar and fat. Hence, the role of physical exertion at work on tobacco and cannabis use and diet rich in sugar and fat should be tackled for information and prevention strategies.
... Two of the medications approved by the FDA for the treatment of opioid use disorder are methadone and buprenorphine. Both medications have demonstrated greater efficacy than counseling alone in decreasing opioid use, increasing retention in substance abuse treatment, and significantly decreasing the risk of overdose and death [13][14][15]. A recent meta-analysis confirmed that patients on methadone maintenance therapy for opioid use disorder had a significantly decreased risk of death during treatment than after cessation; the same analysis suggested buprenorphine is similarly effective [16]. ...
Chapter
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Treatment for opioid use disorders is highly effective yet unavailable in many rural areas. “Somewhere to Go: Ensuring Access to Medication-Assisted Treatment in Rural Maryland” is a Robert Wood Johnson Funded Clinical Scholars project intended to expand the use of tele-health medication-based treatment for opioid use disorders services directly to rural areas in need. We demonstrated that a University-based substance use treatment team can successfully collaborate with a geographically distant rural substance use treatment clinic to provide medication-based treatment for opioid use disorders using a HIPPA compliant telehealth strategy. We provide an overview of the implementation strategies our team used to expand overall access in different locales throughout the State of Maryland and beyond. We describe implementation results of a tele-health medication-based treatment program for opioid use disorders that focuses on implementation successes and how to identify and overcome implementation challenges and barriers. Implementation of a telemedicine approach can be challenging, but careful consideration and forethought can map a successful path to program development, operation and sustainability.
... Since that time, more evidence has emerged which indicates that naltrexone may also be useful for treating methamphetamine dependence (Karila et al, 2010), and certain full or partial opioid agonists, such as methadone or buprenorphine, may significantly aid in the treatment of populations abusing opioid drugs (e.g. Bart, 2012;Gerra et al, 2006). ...
Thesis
The endogenous opioid neurotransmitter system (EOS) has been implicated in a wide array of behavioral processes, including reinforcement, pain modulation, mood disorders, social interactions, and the placebo effect. These intertwining factors make an understanding of the EOS’s role crucial for developing effective therapies for a range of disorders. We used positron emission tomography to investigate whether acute and long-term administration of two drugs of abuse, nicotine and opioid analgesics, are associated with alterations in endogenous mu-opioid neurotransmission. We found that compared to healthy controls, overnight-abstinent smokers showed significant decreases in mu-opioid receptor (MOR) availability in the thalamus and bilateral basal ganglia, regions previously implicated in drug reinforcement and addiction. Moreover, these alterations in neurotransmission were associated with measures of both nicotine dependence and craving. When overnight-abstinent smokers were subsequently given a denicotinized (DN) cigarette to smoke, they showed decreases in MOR availability in the right nucleus accumbens and thalamus, likely related to endogenous opioid release in response to the expectation of receiving nicotine. This placebo effect associated with the DN cigarette appeared to mask the effects of the regular nicotine cigarette smoked afterwards. We also examined how opioid analgesics affect MOR neurotransmission in patients with chronic back pain. Our results indicated that decreases in the integrity of the endogenous opioid system, as indicated by a reduced ability to release endogenous opioids in response to pain, were associated with both higher clinical back pain ratings and with greater hedonic responses to the administration of an exogenous opioid drug. Patients using opioid analgesics for at least one year showed decreased experimental pain-induced MOR activation and a lower number of available free MORs at baseline in regions of the brain implicated in pain modulation and drug abuse, such as the nucleus accumbens and amygdala. With the high prevalence of nicotine smoking, as well as the increasing use of opioid analgesics, it is crucial to understand how endogenous opioid mechanisms are implicated in the reinforcing and long-term effects of these drugs. This knowledge will help suggest avenues to explore while determining what treatments may be most successful in individual patients.
... Opioid maintenance treatment (OMT) or Medication-Assisted Treatment (MAT), which includes psychiatric treatment and psychosocial intervention [3], is the most common treatment for opioid use disorders and has evidence with respect to reductions in drug use, criminal behavior, HIV risk behavior, and mortality [3][4][5][6][7]. OMT was introduced in the 1960s as a treatment for opioid use disorders [8], and at the turn of the century, buprenorphine was added as an alternative treatment option [4,9]. ...
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Opioid use disorders (OUD) is a relapsing condition with high mortality. Opioid maintenance treatment (OMT) reduces heroin use, and overall morbidity and mortality. The prevalence of psychiatric and substance use disorders, potential baseline predictors for psychiatric hospitalization, and psychiatric diagnoses at follow-up were investigated and may give hints about possible preventative strategies. The medical records for 71 patients were reviewed 36 months following referral to OMT from a needle exchange program (NEP). Their psychiatric diagnoses and hospitalizations were identified. Their baseline characteristics were assessed for potential differences between hospitalized versus non-hospitalized patients and between patients with and without psychiatric diagnoses in a longitudinal observational study without controls. A regression analysis was performed to identify predictors for hospitalization when controlling for OMT status. Sixty-five percent of the patients were hospitalized at least once with a psychiatric diagnosis. Substance-related reasons were prevalent, and detoxification occurred among 59% of patients, with sedative- hypnotics (benzodiazepines, zopiclone, zolpidem, and pregabalin) being the substance used by 52% of patients. Baseline use of these drugs and/or buprenorphine predicted for hospitalization when controlling for OMT status. During the follow-up period, 72% of patients met the criteria for a psychiatric diagnosis other than OUD. The prevalence of non-substance use disorders overlapping with SUD was 41%, and that overlapping with anxiety disorder was 27% of all participants. Increased attention to psychiatric co-occurring disorders in the treatment of OUD is required and the importance of addressing sedative-hypnotics use when initiating OMT is highlighted.
... Studies have shown that patients on methadone are usually maintained on 80-120mg oral methadone daily, which is considered a high dose, and 20-60mg, which is considered low dose (16). Patients are usually started at an initial dose of 10-30 mg and can be increased gradually over the first to three weeks (21). Methadone is primarily metabolized by the liver through demethylation by CYP3A4 in addition to numerous other cytochromes (22). ...
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: Opioids are mu receptor agonists and have been an important part of pain treatment for thousands of years. In order to use these drugs appropriately and successfully in patients, whether to control pain, to treat opiate-induced side effects, or opiate withdrawal syndromes, a solid understanding of the pharmacology of such drugs is crucial. The most recognized full agonist opioids are heroin, morphine, codeine, oxycodone, meperidine, and fentanyl. Phenanthrenes refer to a naturally occurring plant-based compound that includes three or more fused rings. The opioids derived from the opium plant are phenanthrene derivatives, whereas most synthetic opioids are simpler molecules that do not have multiple rings. Methadone acts as a synthetic opioid analgesic similar to morphine in both quality and quantity; however, methadone lasts longer and in oral form, has higher efficacy, and is considered a diphenylheptane. Fentanyl is a strong synthetic phenylpiperdine derivative that exhibits activity as a mu-selective opioid agonist approximately 50 to 100 times more potent than morphine. Meperidine is another medication which is a phenylpiperdine. Tramadol is considered a mixed-mechanism opioid drug, as it is a centrally acting analgesic that exerts its effects via binding mu receptors and blocking the reuptake of monoamines. Some of the most common adverse effects shared among all opioids are nausea, vomiting, pruritus, addiction, respiratory depression, constipation, sphincter of Oddi spasm, and miosis (except in the case of meperidine). Chronic opioid usage has also established a relationship to opioid-induced hypogonadism and adrenal suppression. Physicians must be stewards of opioid use and use opioids only when necessary.
... Treatment for opioid use disorder involves pharmacotherapy with opioid substitution treatment (OST) in conjunction with psychosocial interventions. Among the OST medications, methadone is the most commonly used and is effective in improving patient outcomes [11][12][13][14]. Prevalence of cannabis use in patients on methadone maintenance treatment (MMT) is common and higher than prevalence in the general population [15]. ...
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Background Cannabis use during methadone treatment may negatively impact treatment outcomes. The aim of this study was to determine the prevalence and pattern of cannabis use among patients attending a methadone treatment clinic in Nairobi, Kenya. Methods This was a retrospective study of 874 patients on methadone therapy at a methadone maintenance treatment clinic in Nairobi, Kenya from December 2014 to November 2018. Data on sociodemographic characteristics and drug use patterns based on urine drug screens was collected from patient files. Data was analyzed using Statistical Package for the Social Sciences (SPSS) for windows version 23.0. Results Point prevalence of cannabis use was 85.8% (95% CI, 83.3 – 88.0) at baseline and 62.7% (95% CI, 59.5 – 65.8) during follow-up. A pattern of polysubstance use was observed where opioids, cannabis and benzodiazepines were the most commonly used drugs. The mean age of the patients was 35.3 (SD 9.0) years with the majority being male, unemployed (76%), (51.4%) had reached primary level of education, and (48.5%) were divorced or separated. University education was associated with reduced risk for cannabis use OR = 0.1 (95% CI, 0.02-0.8, p = 0.031). Conclusion Cannabis use is prevalent among patients attending a methadone treatment clinic in Kenya, suggesting need for targeted interventions to address the problem of cannabis use during methadone treatment.
... The severity of opioid withdrawal symptoms makes it particularly difficult to recover from opioid dependence. The most common treatment for opioid withdrawal is opioid substitution therapy (Bart 2012) in which opioids with long halflives, such as buprenorphine, are taken once a day to replace the repeated administration of opioids with short half-lives such as heroin. Psychotherapy appears to increase adherence to opioid substitution therapy (Manhapra et al. 2018) without a major direct effect on drug efficacy (Ling et al. 2013;Gregory and Ellis 2020). ...
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Rationale Social support and opioid replacement therapy are commonly used to treat opioid withdrawal. Objective The present study tested the hypothesis that social housing and buprenorphine administration can restore wheel running depressed by morphine withdrawal in rats. Results Experiment 1 assessed disruptive side effects of buprenorphine and found that administration of low doses (3.2, 10, & 32 µg/kg, s.c.) had no impact on voluntary wheel running. Experiment 2 assessed the impact of social housing and acute buprenorphine administration (10 µg/kg) on morphine withdrawal. Two 75 mg morphine pellets were implanted for 3 days to induce dependence. Removal of the morphine pellets caused a decrease in body weight, increase in wet dog shakes, and depression of wheel running during the normally active dark phase of the circadian cycle. Social housing restored wheel running and reduced the number of wet dog shakes but did not affect body weight. Administration of buprenorphine restored wheel running depressed by morphine withdrawal for 2 days in individually housed rats and produced time-dependent changes in socially housed rats: Depression of wheel running in the 3 h following administration and restoration of running subsequently compared to saline-treated controls. Conclusions The impact of buprenorphine and social housing to reduce the effect of morphine withdrawal in rats is consistent with the use of opioid substitution therapy and psychotherapy/social support to treat opioid withdrawal in humans. These data provide further validation for the clinical relevance for the use of wheel running to assess spontaneous opioid withdrawal.
... methadone, buprenorphine, and naltrexone) . However, despite extensive evidence of their effectiveness (e.g., Bart, 2012;Ma et al., 2018;Sordo et al., 2017;Wakeman et al., 2020), gaps in access to MOUD have persisted (e.g. Beetham et al., 2020;David & Carr, 2019;Jones et al., 2015). ...
Article
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Background Recovery housing plays an important role in supporting individuals in their recovery by building recovery capital and providing stable living environments; however, the extent to which medications for opioid use disorder (MOUD), the gold standard for OUD treatment, are accepted in recovery housing settings is unclear. The purpose of this study, as part of a larger statewide evaluation of Missouri recovery homes, was to identify the extent to which Missouri recovery houses were accepting of methadone, buprenorphine, and naltrexone as well as the extent to which the acceptance of each medication was linked to whether the recovery home encouraged tapering off MOUDs. Methods Sixty-four recovery housing managers and/or staff, out of 66 eligible recovery homes in Missouri completed the survey. Results Results indicated that methadone was the least accepted medication for long-term use followed by buprenorphine and then naltrexone. Recovery houses that had significantly lower overall acceptance of methadone encouraged tapering; however, the overall acceptance for buprenorphine and naltrexone was not significantly related to the encouragement of tapering off MOUDs. Conclusion This work highlights the need to develop reliable instruments to measure and assess MOUD-capable recovery homes and to increase knowledge and acceptance of MOUD within recovery home settings.
... This phenomenon most likely accounts for the high mortality rates observed in methadone-prescribed patients in the United Kingdom during the 1990s. 7 Despite its potential benefits, the misuse of methadone highlights its inadequacy in alleviateing the opiate crisis. ...
... Replacement therapy with methadone eases access to this synthetic opioid [1]. Methadone has influential effect in relieve of almost all opioid withdrawal symptoms. ...
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Background: Acute opioid overdose is a common cause of admission in emergency department. In spite of the fact that naloxone is the main therapy for decades, there are controversies about the proper way of its use. This study aimed to compare two most recommended administration modes for naloxone. Methods: In this single-blind clinical trial, 80 patients with methadone overdose syndrome were randomly divided into two equal groups. The patients in infusion group received a constant infusion of naloxone preparation while in the patients in PRN group, naloxone was administered only if needed clinically. Severity of withdrawal syndrome was evaluated after 30 min, 3 h, and 12 h of the treatments in both groups. Results: Eighty patients completed the study (10 women and 70 men). Both groups were similar in terms of mean age, sex ratio, and the severity of intoxication. The severity of withdrawal symptom was significantly lower in the PRN group (P<0.001). Conclusion: Naloxone administration as PRN mode lowers the rate and severity of withdrawal syndrome. It is recommended as the preferred mode of naloxone administration.
... MMT is heavily regulated, creating multiple barriers that restrict its efficacy, 4 although it is widely considered one of the best ways to reduce fatal overdoses and other harms of criminalized opioid use. 5 MMT regulations were relaxed during COVID-19. 6 However, we observed that many MMT programs were not relaxing policies, overdose rates were increasing among our members, and There is a long tradition of using experiential knowledge to advance research; many disciplines, such as critical race studies and disability studies, have recognized its importance. ...
Article
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In this editorial based on the Urban Survivors Union Methadone Manifesto, we focus on a few methadone maintenance treatment barriers we have experienced and suggest improvements. Specifically, we discuss issues during COVID-19, take-home doses, counseling and treatment plans, costs, and issues faced by parenting patients and patients in the sex trades.
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Introduction: Sexual dysfunctions related to the long-term of methadone and buprenorphine are common. In order to investigate the effects of Methadone maintenance therapy (MMT) and buprenorphine maintenance treatment(BMT) on women sexual function with opioid abuse dependence, the present study was performed with aim to evaluate the effect ofmaintenance treatment with methadone and buprenorphine on sexual function of females with opioid abuse dependence .In order to the effective measures regarding choosing the best practice , consultation and decision making will be taken. Methods: This cross-sectional descriptive-analytic study was performed in 2015-2017 on 89 women with opioid abuse. Demographic information, sexual function and satisfaction of women who were previously treated with MMT and BMT were completed and collected using the Female sexual function index(FSFI) and Larson Sexual satisfaction questionnaire (LSSQ) in two stages with an interval of 3 months. Data were analyzed by SPSS software (version 20) and Independent T, Mann-Whitney U and Chi-Square tests. Results: The total scores of FSFI (Female Sexual Function Index) were significantly higher in the BMT group (p < 0.05). The scores of sexual desire and arousal subscales were significantly improved in the BMT group compared with the MMT group (p < 0.05). No significant difference was observed between the two groups in terms of the level of sexual satisfaction in two studied stages (p=0.25). Conclusion: The use of BMT in women with opioid abuse can have a more positive effect on sexual desire and arousal than those in the MMT group. This issue likely leads to more adhesion to the use of maintenance treatment. In other cases, these two drugs are similar in terms of efficacy and causing satisfaction from sexual function.
Article
Existing pharmacotherapies for managing craving, a strong predictor of relapse to automated addictive behaviours, are limited in efficacy and characterised by increased health risks associated with their pharmacological profile. Preclinical studies have identified oxytocin as a promising pharmacotherapy with anti‐craving properties for addictive behaviours. Here, we provide the first systematic review of 17 human studies (N=722; 30% female) investigating the efficacy of intranasal oxytocin to reduce craving or consumption in addictive behaviours. We identify intranasal oxytocin as a method that warrants further investigation regarding its capacity to decrease cue‐induced, acute stress‐induced or withdrawal‐related craving and relapse related to alcohol, cannabis, opioids, cocaine, or nicotine, including a potential role as ad‐hoc medication following exposure to drug‐related cues. Future studies should investigate the role of factors such as treatment regimes and sample characteristics, including the role of the amygdala, which we propose as a distinct mechanism mediating oxytocin's anti‐craving properties.
Article
Background: Adolescents use heroin as well as prescription opioids. Unfortunately, access to care for adolescents and young adults with opioid use disorder is limited. Naltrexone is a mu opioid receptor antagonist which blocks the effects of opioids, prevents intoxication and physiologic dependence. Here, we present literature on the use of naltrexone for adolescents with opioid use disorder. Methods: Electronic databases were searched for scientific literature addressing the use of naltrexone in adolescents with opioid use disorder. Results: Four scientific articles were found to meet inclusion criteria. A retrospective case-series review in Australian hospitals suggests less overdose events after the implantation of extended-release naltrexone pellets. A case series utilizing extended-release naltrexone injection at a community treatment center found 10 of 16 patients remained in treatment for 4 or more months, 9 of 16 had a “good outcome.” Two retrospective cohort studies assessing insurance data found significantly improved retention rates for youth receiving naltrexone compared to behavioral services alone. Conclusion: Preliminary data suggest improved risk of overdose events, retention in treatment, and improved outcomes with the use of extended-release naltrexone for youth struggling with opioid use disorder.
Article
Objectives: Opioid dependence is currently one of the most serious problems affecting the social norms and public health system. Methadone maintenance therapy (MMT) is being widely used in treating heroin-dependent patients. The mechanism of methadone metabolism and disposition has been shown to involve cytochrome P450 (CYP450) and P-glycoprotein. The aim of this study was to explore the relationships among genetic polymorphisms, BMI and effective dose of methadone used in MMT within a northern Taiwan cohort. Methods: One hundred heroin-dependent patients were enrolled in the study. The clinical data gathered included methadone dose, sex and BMI. DNA was collected from the oral swab of the participants to analyze the relevant alleles. Results: An effective methadone dose correlated with sex, BMI and the presence of ABCB1 2677GG (rs2032582) and CYP2B6 516GG (rs374527). Furthermore, the CYP2B6 516GG homozygote was related to a higher average dose of methadone (GG: 68.50 ± 32.43; GT: 52.28 ± 25.75; TT: 44.44 ± 29.64; P < 0.02), whereas the ABCB1 2677GG homozygote was related to a lower dose (GG: 51.09 ± 20.83; GT: 69.65 ± 37.51; TT: 62.52 ± 30.44; P < 0.05). We examined the predictive effect of polymorphisms combined with sex and BMI on methadone dose by conducting multiple linear regressions. Our data predicted the average dose of methadone in approximately 30% of heroin-dependent patients. Conclusion: The interactions between genetic polymorphisms and clinical features proved useful in identifying the effective dose of MMT for heroin-dependent patients in Taiwan more precisely.
Article
Opioid misuse and opioid related deaths continue to affect families and communities across the United States. Medication-assisted treatment (MAT) combines the use of medications and counseling to treat the whole person. While MAT shows promise over counseling-only approaches, there is little research or guidance on how to implement counseling with the medication. The following qualitative study used a phenomenological approach to explore the experiences of ten clients in a MAT program that utilized group therapy with the medication buprenorphine. The findings showed that clients valued the Camaraderie and Feedback they received in group and even times of Discomfort were important.
Article
Several studies have found an association between salivary cortisol levels and dropping out of inpatient substance addiction treatment programs. The results are mixed due to variations in the study design and the lack of standardized routines for cortisol assessment. The aim of this study was to investigate whether there was (1) an association between salivary cortisol levels and dropping out from inpatient substance addiction treatments; (2) higher predictive validity for dropout in one of the cortisol indexes: Area Under the Curve with respect to ground (AUC G ) or Daily Cortisol Slope (DCS); (3) an interaction effect with time for each cortisol index; and (4) different dropout rates for sex and patients in short-term versus long-term treatment programs. This was a prospective, repeated-measures observational study. Patients (n = 173) were recruited from 2 inpatient facilities in the central region of Norway between 2018 and 2021. Salivary cortisol was measured 4 times during the treatment period, with 8 samples collected over 2 consecutive days at each time point. Cortisol levels were calculated using the cortisol indices AUC G and DCS. Dropout was used as the outcome measure at each time point. Associations were calculated using a logistic linear regression. The results suggest a main effect of AUC G , whereby higher levels reduce dropout risk (OR = 0.92, P = .047). An interaction with time in treatment also revealed a higher dropout risk (OR = 1.09, P = .044) during week 4 of the treatment, depending on the AUC G. These results support using AUC G as the recommended index when assessing cortisol, and that the relationship between cortisol levels and length of treatment should be further investigated.
Article
Background and Aims There is mounting evidence that opioid use disorder is experienced differently by people of different genders and race/ethnicity groups. Similarly, in the US access to specific medications for opioid use is limited by gender and race/ethnicity. This study aims to evaluate if gender or race/ethnicity is associated with different rates of treatment retention in the US, for each of three medications used to treat opioid use disorder. Methods A systematic search was conducted using PubMed, CINHAL, and PsychINFO, databases. All studies that provided a ratio of those retained in treatment at a specified time in terms of gender and/or race/ethnicity and medication were included. Variables were created to assess the effects of time in treatment, recruited sample, required attendance at concurrent psychosocial treatment, and adherence to strict rules of conduct for continuation in treatment on retention. Meta-analytical and meta-regression methods were used to compare studies on the ratio of those who completed a specific time in treatment by race/ethnicity group and by gender. Results Nineteen articles that provided the outcome variable of interest were found (11buprenorphine,sixmethadone,andtwonaltrexone). Meta-analyses found that treatment retention was similar for all gender and racial/ethnic groups for all three medications. Meta-regression found that those of the African American group who were recruited into buprenorphine treatment were retained significantly longer than African Americans in buprenorphine treatment who were studied retrospectively. Also, both genders had significantly lower retention in methadone treatment when there was the additional requirement of psychosocial therapy.
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Aim and Background: One of the factors influencing the preparation for addiction is personality traits and temperament. Considering that so far little study has been done on the relationship between different temperaments (mizaj) of Persian medicine and preparation for addiction, the present study aimed to investigate the role of these mizaj in students' preparation for addiction. Methods and Materials: The design of the present study was descriptive cross-sectional. A total of 241 students studying in the universities of Mobarakeh were selected by quota sampling method and answered the Iranian preparation for addiction scale and Mizaj determination questionnaire. After determining the Mizajes of the sample, the average preparation for addiction was compared with 9 types of mizaj using analysis of variance. Findings: The results of analysis of variance showed that the average preparation for addiction in at least one mizaj is significantly different from other mizajes. Examination of the results of LSD post hoc test showed that the mean of preparation for addiction in warm-temperate mizaj was significantly lower than the mean of preparation for addiction in cold-temperate, cold-wet, and cold-dry and hot-dry mizajes. Conclusions: In general, the results of the present study show that people with all types of cold and hot-dry mizajes have the highest vulnerability and people with warm-temperate have the least vulnerability to addiction. These results were explained in the theoretical and research context and traditional medicine strategies in maintaining health and tempering mizajes, to protect the tendency to addiction in people with vulnerable mizajes and prevent the movement of non-vulnerable mizajes to the vulnerable were presented. Keywords: addiction, mizaj, Persian medicine, prevention
Article
Opiates are among the widely abused substances worldwide. Also, the clinical use of opioids can cause unwanted and potentially severe consequences such as developing tolerance and dependence. This study simultaneously measured the changes induced after morphine dependence and naloxone-induced withdrawal syndrome on the resting-state functional connectivity (rsFC) and local field potential (LFP) power in the prefrontal cortex of the rat. The obtained results revealed that acute morphine administration significantly increased the LFP power in all frequency bands, as well as the rsFC strength of the prefrontal cortex, and naloxone injection reversed this effect. In contrast, chronic morphine administration reduced neural activity and general correlation values in intrinsic signals, as well as the LFP power in all frequency bands. In morphine-dependent rats, after each morphine administration, the LFP power in all frequency bands and the rsFC strength of the prefrontal cortex were increased, and these effects were further enhanced after naloxone precipitated withdrawal syndrome. The present study concludes that general correlation merely reflects the field activity of the local cortices imaged.
Article
Background: In 2014, nearly 2.5 million Americans had a substance use disorder for opioids (e.g., prescription pain medication or heroin) with over half estimated to have had prior contact with the criminal justice system. Despite strong evidence that opioid agonist treatment (OAT) is effective in reducing overdose, increasing treatment retention, and improving physical health and well-being outcomes, the use of OAT among justice-involved individuals is relatively rare. Methods: The current study uses national data of publicly funded admissions to substance abuse treatment to assess the extent to which OAT is used for cases referred to treatment by the criminal justice system. We explore the relationship between demographics, substance use severity, and access to treatment and OAT receipt. Results: Findings indicate that fewer than 6% of criminal justice cases received OAT as part of the treatment plan. Those with daily substance use, comorbid psychiatric problems, prior treatment, females, Latinos, and those who were older and those who were living independently were more likely to receive OAT, as were those living in the Northeast and with government health insurance. Conclusions: Improving the integration of the criminal justice system with substance use treatment programs would improve access to care and potentially reduce multiple health disparities faced by those in the justice system. As criminal justice responses to substance use disorder move toward a public health approach, it is imperative that the criminal justice system consider mechanisms for improving access and referrals to OAT.
Article
There is a lack of safe and effective non-opioid medications for the treatment of opioid addiction. Aquaporin-4 (AQP4), a water channel protein expressed in astrocytes, regulates the progression of neurological diseases. Our previous work demonstrated that AQP4 deficiency in mice attenuated morphine-induced physiological dependence. However, the role of AQP4 in the neurobiology of behaviours related to opioid addiction in mice remains unclear. Here, we report that Aqp4-knockout mice exhibited attenuated heroin consumption and heroin-seeking behaviours. Furthermore, Aqp4-knockout mice displayed diminished hyperactivity induced by morphine and heroin and subsequently showed dramatically inhibited morphine-induced behavioural sensitization. This attenuated hyperlocomotion to opioids was accompanied by a decreased dopamine response to the opioid-induced increase in the levels of extracellular dopamine in the NAc. In addition, Aqp4-knockout mice displayed upregulation of dopamine transporters in the striatum, suggesting a probable neurobiological mechanism for uptake of the extracellular dopamine. The present findings suggest that deficiency of AQP4 decreases opiate-induced drug seeking and taking behaviours, and AQP4 may be involved in the treatment of addiction. Therefore, the development of a pharmacological antagonist to AQP4 may be valuable to investigate as opioid addiction therapy.
Article
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We examined the prospective association of physical exertion at work with subsequent tobacco, cannabis, alcohol use, and sugar and fat consumption. Volunteers of the French population-based CONSTANCES cohort currently employed were included from 2012 to 2017 for tobacco and cannabis outcomes (n = 100,612), and from 2012 to 2016 for alcohol and sugar and fat outcomes (n = 75,414). High level of physical exertion at work was defined as a score ≥ 12 at the Rating Perceived Exertion Borg scale. Substance use was self-reported and diet rich in sugar and fat was obtained from principal component analysis and analyzed as quartiles. Generalized linear models computed odds of substance use and sugar and fat consumption at follow-up according to baseline physical exertion at work, while adjusting for sociodemographic factors, depressive symptoms and baseline level of consumption. High physical exertion was associated with tobacco use with dose-dependent relationships. It was also associated with increased odds of cannabis use at least once per month compared to no use in the past and with increased odds of diet rich in sugar and fat. Hence, the role of physical exertion at work on tobacco and cannabis use and diet rich in sugar and fat should be tackled for information and prevention strategies.
Chapter
Integration of opioid use disorder (OUD) treatment in primary care is crucial for expanding access to care. The availability of medications for OUD – in particular, buprenorphine – is the starting point for OUD treatment. Multidisciplinary treatment teams that consist of waivered primary care providers and care coordinators are common to integration. Initial assessments are anchored in confirming a diagnosis of OUD, determining patient readiness and goals for treatment, and planning for the care of comorbid conditions. Polysubstance use is not a contraindication to OUD treatment in primary care. Sublingual buprenorphine, the most widely used medication for OUD in primary care, can be safely initiated in patients using unobserved treatment initiation strategies. Maintaining patients in OUD treatment entails modifying or intensifying treatment according to patient needs. Additional psychosocial counseling beyond the scope of primary care–based OUD treatment should be offered but not required. Finally, a patient-centered approach to utilizing toxicology tests and addressing diversion is essential to integrating OUD treatment in primary care.
Article
Introduction People who use drugs (PWUD) face a multitude of barriers to accessing healthcare and other services. Mobile health clinics (MHC) are an innovative, cost-effective health care delivery approach that increases healthcare access to vulnerable populations and medically underserved areas. There is limited understanding, however, of how PWUD perceive and experience MHCs. Methods Semi-structured interviews were conducted with 31 PWUD – 16 who had received care (clients) on an MHC (The Spot) and 15 who had not (non-clients) – to explore their perceptions and utilization of an MHC partnered with a mobile syringe services program in Baltimore, Maryland. Data analysis of the text was conducted using an iterative thematic constant comparison process informed by grounded theory. Results Clients and non-clients, once aware of the MHC, had positive perceptions of The Spot and its benefits for their individual health as well as for the wellbeing of their community. These sentiments among clients were largely driven by access to low-barrier buprenorphine and service delivery without stigma around drug use. However, lack of general awareness of the spot and specific service offering were barriers to its use among non-clients. Discussion MHCs provide an important opportunity to engage PWUD in healthcare and to expand buprenorphine use; however, even with accessibility near where PWUD access injection equipment, barriers to its use remain. Peer dissemination may be able to facilitate program information sharing and recruitment. • KEY MESSAGES • People who use drugs perceive a mobile health clinic in their neighbourhood as a benefit to their communities and themselves by improving access to healthcare services, providing access to low-threshold buprenorphine dispensation, and offering services without drug use stigma. • People who use drugs learned about a mobile health clinic in their neighbourhood largely through word-of-mouth. As a result, people received limited information about the mobile health clinic services creating a barrier to its use.
Conference Paper
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Introduction: Bronchial carcinoid tumours account for approximately 1–2 % of all lung malignancies in adults and roughly 20–30 % of all carcinoid tumours. The majority of patients with a bronchial carcinoid have a centrally-located tumour and are symptomatic with coughing, haemoptysis, wheezing, or a recurrent post-obstructive pneumonia. Description/case presentation: This patient presented to casualty with similar symptoms on 2 separate occasions, 8 months apart. In both presentations, the patient had been seen by a healthcare professional prior to presentation and had been started on antibiotics for a lower respiratory tract infection (LRTI). On first presentation, in March 2014, the patient was brought in by ambulance due to haemoptysis and right sided pleuritic chest pain. He was diagnosed with an LRTI and was discharged on antibiotics and for follow-up in outpatients (OPD). At OPD, in May 2014, his X-ray showed improvement. In November 2014, he presented again with haemoptysis, right sided pleuritic chest pain and dyspnoea. CT and PET CT showed a right lower lobe mass of 5 cm suggestive of a pulmonary carcinoid without evidence of other masses or metastasis. Diagnostic bronchoscopy failed due to bleeding intraoperatively. A right thoracotomy and bi-lobectomy was performed and histology confirmed the diagnosis of a well differentiated carcinoid tumour in the right main bronchus. Although rare, bronchial carcinoid should be considered in the differential of a patient presenting with haemoptysis, pleuritic chest pain and dyspnoea. If left untreated it may cause acute airway obstruction and/or metastasise to other organs. It is advised to reconsider the diagnosis when a patient’s symptoms do not resolve and presents on multiple occasions. Although rare, an awareness of carcinoid tumours and how they can present is important as it can develop into a life threatening condition.
Chapter
This chapter discusses the evolution of an opioid use disorder as well as treatment approaches, including the medication-assisted treatments of methadone, buprenorphine, and naltrexone and non-pharmacologic interventions. Using the narrative of a case study, readers will improve their understanding on how to diagnose, assess, and treat opioid use disorder. They will also learn how to weigh the pros and cons of the existing medication treatment options and how to begin prescribing these medications to their patients. Issues covered include the role of prescription opioids and untreated pain in the development of an opioid use disorder, misconceptions and stigma about medication-assisted treatment, and the increasing use of kratom, an unscheduled opioid receptor agonist, among patients with opioid use disorder.
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Introduction In the current overdose epidemic, effective treatments for opioid use disorders (OUD), including innovations in medication delivery such as extended-release formulations, have the potential to improve treatment access and reduce treatment discontinuation. This study assessed treatment retention in a primary care–based, extended-release buprenorphine program. Methods The study recruited individuals (n = 92) who transitioned from sublingual buprenorphine to extended-release buprenorphine (BUP-XR) in 2018–2019. The study defined the primary outcome, treatment retention, as three or more consecutive, monthly BUP-XR injections following the transition to BUP-XR in this retrospective chart review. Results Participants' mean age was 38 years old and 67% were male. The average duration of sublingual buprenorphine prior to transition was 17.1 (±28.1) months. Three months after transition, 48% of extended-release buprenorphine patients had discontinued BUP-XR treatment. Persons with chronic pain were more likely, and those who had used heroin in the past month less likely to continue BUP-XR. Mean months on sublingual buprenorphine prior to BUP-XR initiation was 24.3 (±32.5) months for people who received 3+ post-induction injections compared to only 8.9 (±19.5) months for those who did not (p = .009). Conclusions Extended-release buprenorphine discontinuation was high in a real-world setting. Retention continues to represent a major obstacle to treatment effectiveness, and programs need interventions with even newer MOUD formulations.
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The incidence of injection drug use–associated infective endocarditis has been increasing rapidly over the last decade. Patients with drug use–associated infective endocarditis present an increasingly common clinical challenge with poor long-term outcomes and high reinfection and readmission rates. Their care raises issues unique to this population, including antibiotic selection and administration, indications for and ethical issues surrounding surgical intervention, and importantly management of the underlying substance use disorder to minimize the risk of reinfection. Successful treatment of these patients requires a broad understanding of these concerns. A multidisciplinary, collaborative approach providing a holistic approach to treating both the acute infection along with effectively addressing substance use disorder is needed to improve short-term and longer-term outcomes.
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CHOICES was an open-label, randomized, comparative effectiveness trial of office-based extended-release naltrexone versus treatment as usual in people with untreated opioid use disorder and HIV. This study explored facilitators to recruitment in Miami, a successful recruiting site in the national trial. The mixed-methods study included quantitative surveys of randomized participants, medical record abstraction, and qualitative interviews with study staff. Miami recruited 47 (40.5%) of 116 randomized participants in the six-site national trial. In-depth interviews of study staff (n = 6) revealed that Miami had a recruitment approach consisting of street level outreach and a close relationship with the local syringe services program (SSP). Partnership with a local SSP provided access to people living with HIV who inject drugs in Miami. SSPs’ fundamental trust within the community of people who inject drugs can be leveraged in studies aiming to improve health outcomes in this underserved and high-priority population.
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Objective Panic disorder is a debilitating psychiatric disorder that often co-occurs with substance use disorders. Given the current opioid epidemic, the high reported rates of comorbid panic disorder and opioid use disorder are particularly concerning. In this narrative review, we describe the literature on panic disorder and opioid use disorder co-occurrence. Methods: 86 studies, 26 reviews, 2 commentaries, and 5 guidelines pertaining to opioid use disorder, panic disorder, and their comorbidity were identified using all EBSCO databases, PubMed, and Google Scholar. Results: First, we review epidemiological literature on the prevalence of the comorbid condition above and beyond each disorder on its own. Additionally, we discuss the challenges that complicate the differential diagnosis of panic disorder and opioid use disorder and contribute to difficulties establishing rates of comorbidity. Second, we review three theoretical models that have been proposed to explain high rates of co-occurring panic disorder and opioid use disorder: the precipitation hypothesis, the self-medication hypothesis, and the shared vulnerability hypothesis. Third, we outline how co-occurring panic and opioid use disorder may impact treatment for each condition. Conclusion: Based on findings in the field, we provide recommendations for future research as well as treatment considerations for co-occurring panic and opioid use disorders.
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The Emergency Medicine Pharmacist (EMP) is uniquely trained to play a vital role in the management of patients who use opioids and patients with opioid use disorder (OUD). The Emergency Department (ED) is at the forefront of the opioid epidemic, as it serves as a primary place of treatment for patients experiencing opioid overdose, opioid withdrawal, and other complications related to opioid use. Given the size of the epidemic and the limited availability of treatment facilities and providers, the ED provides an opportunity to meet the needs of this patient population. EMPs can take an active role in the expansion of access to treatment of OUD, overdose education and prevention, and harm‐reduction interventions. EMPs have the ability to identify patients who would benefit from therapy, initiate appropriate treatment, provide patient counseling and education, lead the development of institution‐specific protocols and clinical decision tools, and assist in the evaluation of current strategies at their institution. EMPs’ knowledge and understanding of the pharmacology of the medications used to treat OUD is unique and should be utilized to improve patient care for this population. Further, EMPs are poised to limit the emergence of OUD before it begins through the implementation of opioid stewardship activities both within the ED and upon discharge. This paper seeks to review the ways in which EMPs can support efforts in the ED to improve the care of people with OUD. This article is protected by copyright. All rights reserved.
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Substance use disorders among physicians are important and persistent problems. Considerable debate exists over whether use of major opioids, especially among anesthesiologists, is associated with a higher relapse rate compared with alcohol and nonopioids. Moreover, the risk factors for relapse with current treatment and monitoring strategies are unknown. To test the hypothesis that chemically dependent health care professionals using a major opioid (eg, fentanyl, sufentanil, morphine, meperidine) as drug of choice are at higher risk of relapse. Retrospective cohort study of 292 health care professionals enrolled in the Washington Physicians Health Program, an independent posttreatment monitoring program, followed up between January 1, 1991, and December 31, 2001. Factors associated with relapse, defined as the resumption of substance use after initial diagnosis and completion of primary treatment for chemical dependency. Twenty-five percent (74 of 292 individuals) had at least 1 relapse. A family history of a substance use disorder increased the risk of relapse (hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.44-3.64). The use of a major opioid increased the risk of relapse significantly in the presence of a coexisting psychiatric disorder (HR, 5.79; 95% CI, 2.89-11.42) but not in the absence of a coexisting psychiatric disorder (HR, 0.85; 95% CI, 0.33-2.17). The presence of all 3 factors--major opioid use, dual diagnosis, and family history--markedly increased the risk of relapse (HR, 13.25; 95% CI, 5.22-33.59). The risk of subsequent relapses increased after the first relapse (HR, 1.69; 95% CI, 1.13-2.53). The risk of relapse with substance use was increased in health care professionals who used a major opioid or had a coexisting psychiatric illness or a family history of a substance use disorder. The presence of more than 1 of these risk factors and previous relapse further increased the likelihood of relapse. These observations should be considered in monitoring the recovery of health care professionals.
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Background: Overdose deaths involving opioid pain relievers (OPR), also known as opioid analgesics, have increased and now exceed deaths involving heroin and cocaine combined. This report describes the use and abuse of OPR by state. Methods: CDC analyzed rates of fatal OPR overdoses, nonmedical use, sales, and treatment admissions. Results: In 2008, drug overdoses in the United States caused 36,450 deaths. OPR were involved in 14,800 deaths (73.8%) of the 20,044 prescription drug overdose deaths. Death rates varied fivefold by state. States with lower death rates had lower rates of nonmedical use of OPR and OPR sales. During 1999--2008, overdose death rates, sales, and substance abuse treatment admissions related to OPR all increased substantially. Conclusions: The epidemic of overdoses of OPR has continued to worsen. Wide variation among states in the nonmedical use of OPR and overdose rates cannot be explained by underlying demographic differences in state populations but is related to wide variations in OPR prescribing. Implications for Public Health Practice: Health-care providers should only use OPRs in carefully screened and monitored patients when non-OPR treatments are insufficient to manage pain. Insurers and prescription drug monitoring programs can identify and take action to reduce both inappropriate and illegal prescribing. Third-party payers can limit reimbursement in ways that reduce inappropriate prescribing, discourage efforts to obtain OPR from multiple health-care providers, and improve clinical care. Changes in state laws that focus on the prescribing practices of health-care providers might reduce prescription drug abuse and overdoses while still allowing safe and effective pain treatment.
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BACKGROUND Prescription opioid dependence is increasing, but treatment outcomes with office-based buprenorphine/naloxone among these patients have not been described. METHODS We compared demographic, clinical characteristics and treatment outcomes among 200 patients evaluated for entry into a trial of primary care office-based buprenorphine/naloxone treatment stratifying on those who reported exclusive heroin use (n = 124), heroin and prescription opioid use (n = 47), or only prescription opioid use (n = 29). RESULTS Compared to heroin-only patients, prescription-opioid-only patients were younger, had fewer years of opioid use, and less drug treatment history. They were also more likely to be white, earned more income, and were less likely to have Hepatitis C antibodies. Prescription-opioid-only patients were more likely to complete treatment (59% vs. 30%), remained in treatment longer (21.0 vs. 14.2 weeks), and had a higher percent of opioid-negative urine samples than heroin only patients (56.3% vs. 39.8%), all p values < .05. Patients who used both heroin and prescription opioids had outcomes that were intermediate between heroin-only and prescription-opioid-only patients. CONCLUSIONS Individuals dependent on prescription opioids have an improved treatment response to buprenorphine/naloxone maintenance in an office-based setting compared to those who exclusively or episodically use heroin.
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No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription opioids. Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription opioids. In both phases, patients were randomized to standard medical management (SMM) or SMM plus opioid dependence counseling; all received buprenorphine-naloxone. Predefined "successful outcome" in each phase: composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports. During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus opioid dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P < .001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone. Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.
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In an effort to enhance patient safety in opioid treatment programs, the Substance Abuse and Mental Health Saervices Administration convened a multi-disciplinary Expert Panel on the Cardiac Effects of Methadone. Panel members (Appendix A) reviewed the literature, regulatory actions, professional guidances, and opioid treatment program experiences regarding adverse cardiac events associated with methadone. The Panel concluded that, to the extent possible, every opioid treatment program should have a universal Cardiac Risk Management Plan (incorporating clinical assessment, electrocardiogram assessment, risk stratification, and prevention of drug interactions) for all patients and should strongly consider patient-specific risk minimization strategies (such as careful patient monitoring, obtaining electrocardiograms as indicated by a particular patient's risk profile, and adjusting the methadone dose as needed) for patients with identified risk factors for adverse cardiac events. The Panel also suggested specific modifications to informed consent documents, patient education, staff education, and methadone protocols.
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Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.
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Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events. These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).
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To investigate the effect of opiate substitution treatment at the beginning and end of treatment and according to duration of treatment. Prospective cohort study. Setting UK General Practice Research Database. Primary care patients with a diagnosis of substance misuse prescribed methadone or buprenorphine during 1990-2005. 5577 patients with 267 003 prescriptions for opiate substitution treatment followed-up (17 732 years) until one year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice. Mortality rates and rate ratios comparing periods in and out of treatment adjusted for sex, age, calendar year, and comorbidity; standardised mortality ratios comparing opiate users' mortality with general population mortality rates. Crude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100 person years off treatment; standardised mortality ratios were 5.3 (95% confidence interval 4.0 to 6.8) on treatment and 10.9 (9.0 to 13.1) off treatment. Men using opiates had approximately twice the risk of death of women (morality rate ratio 2.0, 1.4 to 2.9). In the first two weeks of opiate substitution treatment the crude mortality rate was 1.7 per 100 person years: 3.1 (1.5 to 6.6) times higher (after adjustment for sex, age group, calendar period, and comorbidity) than the rate during the rest of time on treatment. The crude mortality rate was 4.8 per 100 person years in weeks 1-2 after treatment stopped, 4.3 in weeks 3-4, and 0.95 during the rest of time off treatment: 9 (5.4 to 14.9), 8 (4.7 to 13.7), and 1.9 (1.3 to 2.8) times higher than the baseline risk of mortality during treatment. Opiate substitution treatment has a greater than 85% chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months. Clinicians and patients should be aware of the increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment. Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality.
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Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms. To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence. A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants. After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients. The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24. The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P <.001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P <.001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P<.001) and on the clinician global ratings of improvement (P < .001) than those who received placebo implants. Minor implant site reactions were the most common adverse events: 61 patients (56.5%) in the buprenorphine group and 29 (52.7%) in the placebo group. Among persons with opioid dependence, the use of buprenorphine implants compared with placebo resulted in less opioid use over 16 weeks as assessed by urine samples. clinicaltrials.gov Identifier: NCT00447564.
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To evaluate the impact of introduction of supervision of methadone dosing on deaths related to overdose of methadone in Scotland and England between 1993 and 2008 while controlling for increased prescribing of methadone. Analysis of annual trends in deaths related to overdose of methadone in relation to defined daily doses of methadone prescribed. Scotland and England. Population Deaths in which methadone was coded as the only drug involved or as one of the drugs implicated. Annual OD4-methadone index (number of deaths with methadone implicated per million defined daily doses of methadone prescribed in that year). OD4-methadone declined substantially over the four epochs of four years between 1993 and 2008. It decreased significantly (P<0.05) in 10 of 12 epoch changes: in Scotland from 19.3 (95% confidence interval 15 to 24) to 4.1 (2.8 to 5.4) and finally to 3.0 (2.4 to 3.5) for methadone only deaths (and from 58 to 29 to 14 for deaths with any mention of methadone); in England from 27.1 (25 to 29) to 24.8 (23 to 27) and finally to 5.8 (5.3 to 6.3) for methadone only deaths (and from 46 to 42 to 12 for deaths with any mention of methadone). The decreases in OD4-methadone were closely related to the introduction of supervised dosing of methadone in both countries, first in Scotland (1995-2000) and later in England (1999-2005). These declines occurred over periods of substantial increases in prescribing of methadone (18-fold increase in defined daily doses per million population annually in Scotland and sevenfold increase in England). Introduction of supervised methadone dosing was followed by substantial declines in deaths related to overdose of methadone in both Scotland and England. OD4-methadone index analyses, controlled for substantial increases in methadone prescribing in both countries, identified at least a fourfold reduction in deaths due to methadone related overdose per defined daily dose (OD4-methadone) over this period.
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Offenders with a history of opioid dependence are a particularly difficult group to treat. A large proportion of offenders typically relapse shortly after release from prison, commit drug-related crimes, and then are arrested and eventually re-incarcerated. Previous research demonstrated that oral naltrexone was effective in reducing opioid use and preventing recidivism among offenders under federal supervision. The 111 opioid-dependent offenders in this study were under various levels of supervision that included county and federal probation/parole, a treatment court, an alternative disposition program, and an intermediate punishment program. Subjects were randomly assigned to receive 6 months of either 300 mg per week of oral naltrexone plus standard psychosocial treatment as usual (n = 56) or standard psychosocial treatment as usual (TAU) without naltrexone (n = 55). While the TAU subjects who remained in treatment used more opioids than the naltrexone subjects who remained, the high dropout rate for both groups made it difficult to assess the effectiveness of naltrexone. The study provides limited support for the use of oral naltrexone for offenders who are not closely monitored by the criminal justice system.
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Sublingual 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). Intravenous 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. Intravenous 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. These 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.
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Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area.
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Buprenorphine has recently been reported to be an alternative to methadone and LAAM for maintenance treatment of opioid dependent individuals, differing results are reported concerning its relative effectiveness indicating the need for an integrative review. OBJECTIVES: To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use. SEARCH STRATEGY: We searched the following databases up to 2001, inclusive: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and published reviews and authors of identified RCT's were asked about any other published or unpublished relevant RCT. SELECTION CRITERIA: Randomised clinical trials of buprenorphine maintenance compared with either placebo or methadone maintenance for opioid dependence. DATA COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and independently, rating methodological quality of concealment of allocation; data were extracted independently for meta-analysis and double-entered. MAIN RESULTS: Thirteen studies met the inclusion criteria, all were randomised clinical trials, all but one were double-blind. The method of concealment of allocation was not clearly described in 11 of the studies, otherwise methodological quality was good. Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI: 0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for high dose buprenorphine over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo. REVIEWER'S CONCLUSIONS: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages.
Chapter
This chapter discusses the relationships between endocrine functions and substance-abuse syndromes. Important possible relationships between endocrine function, substance abuse, and addiction syndromes in general, including the early hypothesis that abnormalities in stress responsivity might contribute to the pathophysiology of these disorders, were first formally recognized in the late 1960s. Research reports that focused on the impact of one of the most devastating illicit drugs of abuse, heroin, on various specific components of endocrine function during cycles of addiction, as well as the very early reports on normalization of the perturbations caused by this short-acting opiate on endocrine function during long-term pharmacotherapy with the long-acting opioid agonist, methadone, first appeared in the early 1970s. Studies of both heroin addicts and former addicts in methadone maintenance treatment have been conducted in various therapeutic settings over the ensuing 30 years.
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There is an unknown but very large number of individuals who have experienced and successfully resolved dependence on alcohol or other drugs. These individuals refer to their new sober and productive lifestyle as “recovery.” Although widely used, the lack of a standard definition for this term has hindered public understanding and research on the topic that might foster more and better recovery-oriented interventions. To this end, a group of interested researchers, treatment providers, recovery advocates, and policymakers was convened by the Betty Ford Institute to develop an initial definition of recovery as a starting point for better communication, research, and public understanding. Recovery is defined in this article as a voluntarily maintained lifestyle composed characterized by sobriety, personal health, and citizenship. This article presents the operational definitions, rationales, and research implications for each of the three elements of this definition.
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Objective.— To provide clinicians, patients, and the general public with a responsible assessment of the effective approaches to treat opiate dependence. Participants.— A nonfederal, nonadvocate, 12-member panel representing the fields of psychology, psychiatry, behavioral medicine, family medicine, drug abuse, epidemiology, and the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 600. Presentations and discussions were divided into 3 phases over 212 days: (1) presentations by investigators working in the areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that are part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of a third day. The conference was organized and supported by the Office of Medical Applications of Research, National Institutes of Health. Evidence.— The literature was searched through MEDLINE and other National Library of Medicine and online databases from January 1994 through September 1997 and an extensive bibliography of 941 references was provided to the panel and the conference audience. Experts prepared abstracts for their presentations as speakers at the conference with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. Consensus Process.— The panel, answering predefined questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. Conclusions.— Opiate dependence is a brain-related medical disorder that can be effectively treated with significant benefits for the patient and society, and society must make a commitment to offer effective treatment for opiate dependence to all who need it. All persons dependent on opiates should have access to methadone hydrochloride maintenance therapy under legal supervision, and the US Office of National Drug Control Policy and the US Department of Justice should take the necessary steps to implement this recommendation. There is a need for improved training for physicians and other health care professionals. Training to determine diagnosis and treatment of opiate dependence should also be improved in medical schools. The unnecessary regulations of methadone maintenance therapy and other long-acting opiate agonist treatment programs should be reduced, and coverage for these programs should be a required benefit in public and private insurance programs.
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Heroin, as used by addicts, produces quite different effects than are seen with use of narcotic drugs in ordinary medical practice. Addicts inject themselves repeatedly with larger doses of a narcotic than are usually prescribed for analgesia, and develop modified responses to the drug. In particular, the euphoric effect appears to be a learned phenomenon, like pleasure from smoking; the first shots of heroin taken by a curious adolescent are more likely to cause nausea than pleasure. Later, the euphoric experience becomes central to the addict's life and leaves little room for other interests. With continued use of narcotics, however, the addict finds it progressively more difficult to achieve euphoria, because a chronic exposure to narcotic drug induces a state of tolerance that diminishes the euphoric response. At the same time the increase in physical dependence obliges the subject to continue drug use or suffer abstinence. An advanced state of
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• Buprenorphine was evaluated for its abuse potential and utility in treating narcotic addiction. The drug was morphine-like but was 25 to 50 times more potent than morphine and was longer-acting. Little if any physical dependence of clinical significance was produced by buprenorphine. The effects of morphine to 120-mg doses were blocked by buprenorphine, a blockade that persisted for 291/2 hours. In man, buprenorphine has less intrinsic activity than morphine, and as such, has a low abuse potential. Moreover, the drug has potential for treating narcotic addiction since it is acceptable to addicts, is long-acting, produces a low level of physical dependence such that patients may be easily detoxified, is less toxic than drugs used for maintenance therapy, and blocks the effects of narcotics.
Article
Detoxification was studied in well-rehabilitated, selected, methadone-maintained patients. Seventy-nine percent of 48 patients were successfully detoxified, functioned well, and were apparently drug-free when studied months after their last methadone treatment. Twenty-one percent returned to methadone maintenance treatment because of heroin use or the withdrawal syndrome. Other patients could not be detoxified, even in a slow, flexible dose-reduction regimen. It is recommended that the primary aim of methadone treatment is to facilitate rehabilitation. Decisions regarding detoxification should be made by the physician on an individual basis, after a year or more of successful treatment after weighing the degree of rehabilitation, relapse potential, and the patient's wishes.
Article
A group of 22 patients, previously addicted to diacetylmorphine (heroin), have been stabilized with oral methadone hydrochloride. This medication appears to have two useful effects: (1) relief of narcotic hunger, and (2) induction of sufficient tolerance to block the euphoric effect of an average illegal dose of diacetylmorphine. With this medication, and a comprehensive program of rehabilitation, patients have shown marked improvement; they have returned to school, obtained jobs, and have become reconciled with their families. Medical and psychometric tests have disclosed no signs of toxicity, apart from constipation. This treatment requires careful medical supervision and many social services. In our opinion, both the medication and the supporting program are essential.
Article
Background: The purposes of this study were to investigate the pharmacokinetics of methylphenidate hydrochloride (Ritalin) in the human brain, to compare them with those of cocaine, and to evaluate whether cocaine and methylphenidate compete for the same binding sites.Methods: We used positron emission tomography to measure the temporal and spatial distribution of carbon 11 (11C)-labeled methylphenidate. These results were compared with those obtained previously for [11C]cocaine. Eight healthy male subjects, 20 to 51 years of age, were scanned with [11C]methylphenidate. Three were tested twice to assess test-retest variability, four were tested at baseline and after administration of methylphenidate, and one was tested with [11C]methylphenidate and [11C]cocaine. Two baboons were scanned to evaluate whether there was competition between cocaine and methylphenidate for the same binding sites in the brain.Results: The uptake of [11C] methylphenidate in the brain was high (mean±SD, 7.5%±1.5%), and the maximal concentration occurred in striatum. Pretreatment with methylphenidate decreased binding only in striatum (40%). Although the regional distribution of [11C]methylphenidate was identical to that of [11C] cocaine and they competed with each other for the same binding sites, these two drugs differed markedly in their pharmacokinetics. Clearance of [11C]methlphenidate from striatum (90 minutes) was significantly slower than that of [11C]cocaine (20 minutes). For both drugs, their fast uptake in striatum paralleled the experience of the "high." For methylphenidate, the high decreased very rapidly despite significant binding of the drug in the brain. In contrast, for cocaine, the decline in the high paralleled its fast rate of clearance from the brain.Conclusion: We speculate that because the experience of the high is associated with the fast uptake of cocaine and methylphenidate in the brain, the slow clearance of methylphenidate from the brain may serve as a limiting factor in promoting its frequent self-administration.
Article
Background: Buprenorphine is a partial agonist at the μ-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixeddose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance. Methods: Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period. Results: Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted. Conclusions: Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage.
Article
Context Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. Objective To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. Design A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Setting Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. Participants One hundred ninety-two eligible clinic patients. Intervention Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n=97) or 80 to 100 mg (n=95), with concurrent substance abuse counseling. Main Outcome Measures Opioid-positive urinalysis results and retention in treatment. Results By intent-to-treat analysis, through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval {CI}, 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047). These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Conclusions Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opiod use.
Article
The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex- and age-matched controls. ACTH, β-lipotrophin, (β-LPH), β-endorphin (β-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (β-LPH and β-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a. m. the next morning. The means of the two 8 a.m. measurements of β-LPH (2.67 ± 0.34 fmol/ml, mean ± se), ACTH (2.74 ± 0.71) and cortisol (218 ± 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 ± 0.61, 10.1 ± 0.74 and 364 ± 27, respectively, P < 0.01) while β-EP concentrations in heroin addicts (5.1 ± 0.6) were similar to those of healthy volunteers (6.44 ± 0.56). In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol. In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only. These data show a decreased basal β-LPH, ACTH and cortisol secretion in heroin addicts, despite normal β-EP levels. This would indicate that anterior pituitary proopiocortin synthesis and/or secretion is affected in these subjects, and that there is also some impairment in the structures controlling the circadian rhythmicity of ACTH and related peptides.
Article
Because the pharmacologic properties of 6-dimethylamino-4-4-diphenyl-heptanone-3 ( methadon)1 resemble those of morphine and because methadon has been shown to be an effective analgesic substance in animals and in man,2 studies of the development of tolerance to certain actions of the drug and of its liability to cause addiction have been carried out by the United States Public Health Service. Since the drug may soon come into clinical use the purpose of the present report is to summarize briefly the data collected to date and to present an opinion of the liability of the drug to cause addiction. More detailed reports are to be published later.I. ANIMAL EXPERIMENTS (a) Tolerance.— Thermal stimulation being used,3 partial tolerance developed to the analgesic action in mice after administration of 5 mg. per kilogram subcutaneously once daily for twenty-nine days. In that period the degree of analgesic response was reduced nearly 50
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Legislators, journalists and concerned citizens in general, when considering what to do about the plague of heroin addiction in large cities, ask an obvious question: "Is methadone treatment effective?" The present study, sponsored by the National Institute on Drug Abuse, was undertaken to provide an authoritative answer to this question. Under the direction of a distinguished expert, the evaluation team made an intensive examination of techniques and outcomes in six different methadone programs located in New York, Philadelphia, and Baltimore, and followed this by two years of data analysis and literature review. The present report is the product of this work. In the present study the evaluators selected a set of programs with considerable variance in treatment techniques, and therefore for the first time in evaluation history were able to join a statistical analysis of process to an analysis of outcome. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Stays of 3 months or longer in drug abuse treatment generally predict better follow-up outcomes. In a national sample of community-based programs that participated in the Drug Abuse Treatment Outcome Study, median lengths of stay were 3 months for clients in long-term residential and outpatient drug-free treatments and 1 year for clients in outpatient methadone treatment. However, individual programs within each of these modalities differed widely in how long they kept their clients in treatment as well as their service delivery. Programs treating individuals with heavier cocaine and alcohol use and more psychological dysfunction usually had shorter retention rates. Nonetheless, even after statistically controlling for these client differences, some programs were more effective than others in engaging and retaining clients. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Anesthesiologists with opioid use disorders are at high risk for relapse. In 2005, the impaired professionals monitoring program of the State of Florida implemented a policy whereby anesthesiologists referred for opiate use disorders were contractually obligated to take naltrexone for 2 years. Naltrexone ingestion was witnessed and verified via random urine drugs screens or administered via intramuscular injection. Charts were reviewed for the 11 anesthesiologists who underwent mandated pharmacotherapy with naltrexone, and 11 anesthesiologists who began monitoring immediately before implementation of this policy. Eight of 11 anesthesiologists who did not take naltrexone experienced a relapse on opiates. Only 1 of 11 anesthesiologists experienced a relapse on opiates after taking naltrexone, whereas another relapsed on an inhalant (nitrous oxide). It is noteworthy that 5 of the 11 anesthesiologists who took naltrexone had relapsed before naltrexone treatment, and 7 of the 11 anesthesiologists who did not take naltrexone experienced multiple documented relapses. Only 1 of the 11 anesthesiologists who did not take naltrexone successfully returned to the practice of anesthesiology. This individual suffered primarily from alcohol dependence, and suspected opiate abuse was never verified. Others who attempted return to anesthesiology (n = 7) suffered a relapse. In comparison, 9 of the 11 anesthesiologists who took naltrexone have returned to the practice of anesthesiology without a relapse (as verified by continued random urine and hair testing). Mandatory naltrexone treatment may provide anesthesiologists with an additional safeguard to successfully return to work.
Article
Injecting drug use is an important risk factor for transmission of viral hepatitis, but detailed, transparent estimates of the scale of the issue do not exist. We estimated national, regional, and global prevalence and population size for hepatitis C virus (HCV) and hepatitis B virus (HBV) in injecting drug users (IDUs). We systematically searched for data for HBV and HCV in IDUs in peer-reviewed databases (Medline, Embase, and PsycINFO), grey literature, conference abstracts, and online resources, and made a widely distributed call for additional data. From 4386 peer-reviewed and 1019 grey literature sources, we reviewed 1125 sources in full. We extracted studies into a customised database and graded them according to their methods. We included serological reports of HCV antibodies (anti-HCV), HBV antibodies (anti-HBc), or HBV surface antigen (HBsAg) in studies of IDUs with more than 40 participants (<100% HIV-positive) and sampling frames that did not exclude participants on the basis of age or sex. With endorsed decision rules, we calculated prevalence estimates with anti-HCV and anti-HBc as proxies for exposure and HBsAg as proxy for current infection. We combined these estimates with IDU population sizes to calculate the number of IDUs with positive HBV or HCV statuses. We located eligible reports with data for prevalence of anti-HCV in IDUs for 77 countries; midpoint prevalence estimates suggested 60-80% of IDUs had anti-HCV in 25 countries and more than 80% of IDUs did so in 12 countries. About 10.0 million (range 6.0-15.2) IDUs worldwide might be anti-HCV positive. China (1.6 million), USA (1.5 million), and Russia (1.3 million) had the largest such populations. We identified eligible HBsAg reports for 59 countries, with midpoint prevalence estimates of 5-10% in 21 countries and more than 10% in ten countries. Worldwide, we estimate 6.4 million IDUs are anti-HBc positive (2.3-9.7 million), and 1.2 million (0.3-2.7 million) are HBsAg positive. More IDUs have anti-HCV than HIV infection, and viral hepatitis poses a key challenge to public health. Variation in the coverage and quality of existing research creates uncertainty around estimates. Improved and more complete data and reporting are needed to estimate the scale of the issue, which will inform efforts to prevent and treat HCV and HBV in IDUs. WHO and US National Institutes of Health (NIDA R01 DA018609).