Treatment Of Opioid Dependence Research Articles

AI-assisted de novo design of selective κ-opioid receptor antagonists for the treatment of opioid addiction.

Daunting estimates of overdose fatalities, costs of healthcare, lost productivity, and criminal justice involvement for the misuse of prescription opioids have converted opioid use disorders into a major national crisis in the United States. Among likely efficacious pharmacological interventions for the treatment of opioid dependence are those that can attenuate brain reward deficits experienced during periods of abstinence. Pharmacological blockade of κ-opioid receptors (KOR) has been shown to abolish brain reward deficits detected in rodents during withdrawal from opioids, as well as to reduce the escalation of opioid use in rats with extended access to opioids. Although KOR antagonists represent promising candidates for the treatment of opioid addiction, very few potent selective KOR antagonists are known to date and most of them exhibit significant safety concerns. Here, we used a deep learning framework for the de novo design of ligands with predefined molecular properties to predict new chemotypes with KOR antagonistic activity. Specifically, we pre-trained a deep generative tensorial model to learn a mapping of the chemical space from a ZINC subset of purchasable drug-like molecules, as well as sets of effective (IC50 < 1 µM) or less effective (IC50 ≥ 1 µM) known KOR inhibitors from the ChEMBL database, while simultaneously encoding the relationship between the molecules and their properties. Subsequently, we biased the resulting generative model towards the development of putative KOR antagonists with a reinforcement learning algorithm that rewarded similarity to the antagonist binding mode revealed by the JDTic-bound KOR crystal structure, as well as novelty, synthetic accessibility, absence of unstable and reactive moieties, drug-like solubility, and blood-brain barrier permeability. The generated molecules were prioritized for chemical synthesis and functional evaluation based on their predicted optimal interactions with the receptor.

AATOD's Parrino focusing on the star: Part 8 NPRM

With all of the buzz swirling about buprenorphine — the victory of eliminating the X‐waiver claimed by Congress, the White House, the American Society of Addiction Medicine, the U.S. Department of Health and Human Services, the National Institute on Drug Abuse, the Substance Abuse and Mental Health Services Administration (SAMHSA), the Drug Enforcement Administration, and on and on — what is the main organization dedicated to the treatment of opioid use disorder (OUD) with methadone (and buprenorphine), i.e., the American Association for the Treatment of Opioid Dependence (AATOD), up to? AATOD is looking carefully at, and responding to, the Part 8 Notice of Proposed Rulemaking (NPRM), which makes methadone treatment much more accessible and flexible than it was.

Predicting Patient Satisfaction With Medications for Treating Opioid Use Disorder: Case Study Applying Natural Language Processing to Reviews of Methadone and Buprenorphine/Naloxone on Health-Related Social Media.

Medication-assisted treatment (MAT) is an effective method for treating opioid use disorder (OUD), which combines behavioral therapies with one of three Food and Drug Administration-approved medications: methadone, buprenorphine, and naloxone. While MAT has been shown to be effective initially, there is a need for more information from the patient perspective about the satisfaction with medications. Existing research focuses on patient satisfaction with the entirety of the treatment, making it difficult to determine the unique role of medication and overlooking the views of those who may lack access to treatment due to being uninsured or concerns over stigma. Studies focusing on patients' perspectives are also limited by the lack of scales that can efficiently collect self-reports across domains of concerns. A broad survey of patients' viewpoints can be obtained through social media and drug review forums, which are then assessed using automated methods to discover factors associated with medication satisfaction. Because the text is unstructured, it may contain a mix of formal and informal language. The primary aim of this study was to use natural language processing methods on text posted on health-related social media to detect patients' satisfaction with two well-studied OUD medications: methadone and buprenorphine/naloxone. We collected 4353 patient reviews of methadone and buprenorphine/naloxone from 2008 to 2021 posted on WebMD and Drugs.com. To build our predictive models for detecting patient satisfaction, we first employed different analyses to build four input feature sets using the vectorized text, topic models, duration of treatment, and biomedical concepts by applying MetaMap. We then developed six prediction models: logistic regression, Elastic Net, least absolute shrinkage and selection operator, random forest classifier, Ridge classifier, and extreme gradient boosting to predict patients' satisfaction. Lastly, we compared the prediction models' performance over different feature sets. Topics discovered included oral sensation, side effects, insurance, and doctor visits. Biomedical concepts included symptoms, drugs, and illnesses. The F-score of the predictive models across all methods ranged from 89.9% to 90.8%. The Ridge classifier model, a regression-based method, outperformed the other models. Assessment of patients' satisfaction with opioid dependency treatment medication can be predicted using automated text analysis. Adding biomedical concepts such as symptoms, drug name, and illness, along with the duration of treatment and topic models, had the most benefits for improving the prediction performance of the Elastic Net model compared to other models. Some of the factors associated with patient satisfaction overlap with domains covered in medication satisfaction scales (eg, side effects) and qualitative patient reports (eg, doctors' visits), while others (insurance) are overlooked, thereby underscoring the value added from processing text on online health forums to better understand patient adherence.

Treatment Satisfaction Questionnaire for Medication (TSQM Version II): A Psychometric Properties Analysis

Background: Methadone or buprenorphine maintenance therapy is an effective treatment for opioid dependence. Since the satisfaction of patients under methadone maintenance treatment (MMT) plays an important role in their therapeutic success, it seems important to evaluate the satisfaction of methadone usage using multidimensional psychometric tools. Objectives: The current study aimed to investigate the psychometric properties of the Persian version of the Treatment Satisfaction Questionnaire for Medication (TSQM) version II. Patients and Methods: This cross‑sectional study was carried out on 288 opioid-dependent patients of Shahid Beheshti MMT clinic in Kerman, Iran, selected using the convenience sampling method. The data were collected using a questionnaire containing the demographic characteristics of the participants and the Persian version of the TSQM version II containing 11 items in four subscales of effectiveness, side effects, convenience of use, and overall satisfaction. The sum of the scores of each subscale is displayed as a number from 0 to 100. The face and content validity of the questionnaire was confirmed. The construct validity was assessed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The internal consistency and repeatability of the TSQM version II were determined using Cronbach’s alpha and test-retest methods, respectively. LISREL software (version 8.8) and SPSS software (version 20.0) were used to analyze the data. Results: The sample with the male majority of 85% had a mean age of 46.24 ± 11.5 years. As a measure of internal consistency, Cronbach’s alpha of the Persian version of the TSQM version II was 0.8. The repeatability of the questionnaire using the test-retest method was calculated at 0.9. The EFA revealed the adequacy of sampling and justifiability of the analysis (Kaiser‑Meyer‑Olkin = 0.82, P = 0.001, χ2 = 1507.02, df = 28). In CFA, the goodness of fit was at an appropriate level. Conclusions: The TSQM Persian version can be used as an effective and consistent tool to assess treatment satisfaction in clinical settings.

SAMHSA‐funded OTP census reveals 91% of patients get liquid methadone

An extraordinary (because it is the first time documenting actual patients) research project, a census of all patients in all opioid treatment programs (OTPs), has been under way by the National Association of Alcohol and Drug Abuse Directors (NASADAD) and the American Association for the Treatment of Opioid Dependence (AATOD). Last week, the two organizations released the results of the census, which was conducted on all OTPs certified by the Substance Abuse and Mental Health Services Administration (SAMHSA) (1,826 OTPs) and had an 85% response rate (1,547 OTPs). A total of 512,224 patients in OTPs were reflected in the survey, which is not an extrapolation — it is a head‐by‐head count, not patient‐identified. The State Opioid Treatment Authorities (SOTAs), part of NASADAD, helped collect the data.

GC-MS Analysis of Methadone and EDDP in Addicted Patients under Methadone Substitution Treatment: Comparison of Urine and Plasma as Biological Samples

(1) Background: Methadone, along with buprenorphine, is the most commonly used drug for the treatment of opioid dependence. This study aimed to analyze methadone and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenyl pyrrolidine (EDDP), in the urine and plasma of opiate addicts. The study group consisted of drug users voluntarily admitted to the detoxification center C.E.T.T.T. "St. Stelian" of Bucharest. Secondly, the study aimed to identify whether urine or plasma provides better results for the proposed method. (2) Methods: A GC-MS method, using an internal standard (diphenylamine) in the FULL-SCAN and SIM modes of operation and using the m/z = 72 ion for methadone and the m/z = 277 ion for EDDP, combined with a liquid-liquid extraction procedure was performed. (3) Results: The applied procedure allows the detection and quantification of methadone in both urine and plasma samples. EDDP was identified in patients with higher levels of methadone. Higher levels of methadone were detected in urine than in plasma samples. (4) Conclusions: This procedure can be used in clinical laboratories for the rapid determination of methadone levels in urine rather than in plasma. The procedure can be applied for the monitoring of methadone substitution treatment.

The Social, Material, and Temporal Effects of Monthly Extended-Release Buprenorphine Depot Treatment for Opioid Dependence: An Australian Qualitative Study

Aims: This study examined the social, material and temporal effects of extended-release buprenorphine depot treatment (BUP-XR), among a group of participants commencing BUP-XR in Australia, and considered the situated potentials of these new opioid agonist treatment technologies. Methods: Using a longitudinal qualitative design, 36 participants (25 men, 11 women; mean age 44 years) were interviewed, with 32 followed-up, to generate accounts of BUP-XR experiences. Analysis was informed by sociological approaches which attend to the multiple effects of novel health interventions as they are put to use and made to work, with a focus on tracing change over time. Analysis: The shift from daily to monthly dosing altered how opioid agonist treatment was experienced, reconfigured participants’ relationship to treatment, and affected the temporal patterns of participants’ lives. Extending temporal relations released participants from short-term cycles of living and produced different forms of subjectivity, bringing about both transformation and loss. Monthly dosing, and a sense of normalcy characterized by absenting the routines and felt effects of drugs or treatment medications, potentiated a feeling of stability for many participants. For some, disrupting daily routines precipitated disconnection from treatment and social care relations. The transition from daily to monthly dosing required adaptation and new ways of engaging with treatment and care, with medication acting as a bridge to care without necessarily being the focal point. Conclusions: As BUP-XR treatment gains traction internationally, it will be important to attend to the multiple, and sometimes unexpected, effects this intervention makes in the social and material lives of clients. How choice, social connection, and care can be maintained to help secure BUP-XR’s longer-term impact, and how clients can be supported to adjust to what is felt to be a new normal, will be considerations in future treatment delivery.

AATOD CEO stresses organization's focus on reform

With just over 1,500 attendees, the meeting of the American Association for the Treatment of Opioid Dependence (AATOD) in Baltimore this month was full of information. “I had positive feedback about conference participants learning from the sessions,” AATOD CEO Mark Parrino told ADAW last week. “The plenary sessions provided excellent guidance on the progress that has been made at the federal and state level,” he said.

AATOD fact‐checks methadone/buprenorphine bills

There are two bills currently in Congress that affect methadone and buprenorphine treatment for opioid use disorder (OUD), and there is still much confusion about support from the American Association for the Treatment of Opioid Dependence (AATOD).

AATOD conference features harm reduction session

The first in-person conference since COVID-19 of the American Association for the Treatment of Opioid Dependence (AATOD) held in Baltimore last week included sessions on harm reduction, including one that featured Chase Holleman as a speaker. Holleman is the new lead for harm reduction at the Substance Abuse and Mental Health Services Administration (SAMHSA). In recovery from opioid use disorder (OUD), Holleman is also a licensed clinical social worker and a licensed addiction specialist who helped found a harm reduction center in Greensboro, North Carolina with Louise Vincent of the Drug Users Union.

In Case You Haven't Heard…

Last week in Baltimore, in a hotel across the street from the conference center of the American Association for the Treatment of Opioid Dependence, a staffer shared some reflections on methadone with us. He said he knew too many people who were taking methadone in an OTP and supplementing with street drugs they bought for $1, and that he believed treating trauma and learning humility were equally important as the medication. He supported overdose prevention centers as safe places for drug users to go. And he credited Narcotics Anonymous for helping many people get to know themselves, and come out healthy. Just another view from the real world.

The Impact of Temperament and Character on Treatment Compliance of Opioid Agonists

Background: Opioid agonist treatment, as the most effective treatment for opioid dependency, requires patient adherence for its effectiveness over the long run. Previous studies on psychiatric and non- psychiatric patients indicated that the patient`s temperament has had effect on their treatment compliance. Some studies on different types of addiction have attributed special temperament and character traits to these patients. Introduction: This study aims to investigate the impact of temperament and characteristics on opioid treatment compliance. In this study, the relationship between demographic variables, type of medication therapy, and temperament and characteristics scales of patients against opioid agonists therapy compliance was examined Methods: In this cross-sectional study, 150 patients who had initiated the course of opioid agonist maintenance therapy underwent TCI 125-item test and were followed-up for 2 months regarding compliance. The data were inputted into SPSS 24. K-S and Mann-Whitney U tests were employed to explore the relationship between quantitative and qualitative variables, while for examining the relationship between qualitative variables with each other, Chi-square test was utilized. The significance level in the tests was considered p&lt;0.05. Result: The treatment compliance in this study was 67.2%. In patients who did not have treatment compliance, scores of novelty-seeking (16.7±7versus11.7±4, p&lt;0.001), harm avoidance (16.5±5versus 11.8±5, p&lt;0.0001), reward dependence (12.4±3 versus 10.2±3, p=0.005) and self-transcendence (10.6±2 versus 8.7±2 p=0.002) were higher, but in those who had suitable treatment compliance, scores of persistence (3.5±1 versus 2.3±1, p=0.004) and cooperativeness (17.6±3 versus14.8±4, p=0.004) were higher. Further, some temperament traits were different among patients undergoing treatment with buprenorphine versus methadone (scores of persistence, self-directedness and self-transcendence were higher in the group receiving buprenorphine, while scores of harm avoidance and cooperativeness were higher in the group under methadone treatment). There was also a significant relationship between gender (good compliance: female 100%, male 65%, poor compliance female 0%, male 35%; p=0.04), level of education (higher), as well as type of medication (buprenorphine) and treatment compliance. Conclusion: The results of this study can help to identify high-risk individuals for withdrawing opioid addiction. These people can be a target for pharmacological and non-pharmacological interventions to have their personality traits modified. Investigation of the effect of performing these interventions on treatment compliance can be a subject of future study in this area. Also while there are differences in personality characteristics among cultures, this study investigated Iranian culture more precisely.

Current and emerging pharmacotherapies for opioid dependence treatments in adults: a comprehensive update

Introduction Opioid use disorder (OUD) is characterized by compulsive opioid seeking and taking, intense drug craving, and intake of opioids despite negative consequences. The prevalence of OUDs has now reached an all-time high, in parallel with peak rates of fatal opioid-related overdoses, where 15 million individuals worldwide meet the criteria for OUD. Further, in 2020, 120,000 opioid-related deaths were reported worldwide with over 75,000 of those deaths occurring within the United States. Areas covered In this review, we highlight pharmacotherapies utilized in patients with OUDs, including opioid replacement therapies, and opioid antagonists utilized for opioid overdoses and deterrent of opioid use. We also highlight newer treatments, such as those targeting the neuroimmune system, which are potential new directions for research given the recently established role of opioids in activating neuroinflammatory pathways, as well as over the counter remedies, including kratom, that may mitigate withdrawal. Expert opinion To effectively treat OUDs, a deeper understanding of the current therapeutics being utilized, their additive effects, and the added involvement of the neuroimmune system are essential. Additionally, a complete understanding of opioid-induced neuronal alterations and therapeutics that target these abnormalities – including the neuroimmune system – is required to develop effective treatments for OUDs.

Opioid treatment worldwide conference set for Baltimore next week

More than 1,200 leaders in opioid treatment plan to convene in Baltimore later this month for the first in‐person conference of the American Association for the Treatment of Opioid Dependence (AATOD) since October 2019. Speakers including Rahul Gupta, M.D., director of the White House Office of National Drug Control Policy (ONDCP), and Miriam Delphin‐Rittmon, Ph.D., leader of the Substance Abuse and Mental Health Services Administration (SAMHSA) and assistant secretary for mental health and substance use of the Department of Health and Human Services. In addition to these federal officials, others, including from SAMHSA and ONDCP, plan to be there to present and answer questions.

Coming Up…

The 2022 American Association for the Treatment of Opioid Dependence (AATOD) conference will be held in Baltimore Oct. 30–Nov. 3. For more information, go to https://www.eventscribe.net/2022/AATOD/

Coming Up…

The 2022 American Association for the Treatment of Opioid Dependence (AATOD) conference will be held in Baltimore Oct. 30–Nov. 3. For more information, go to https://www.eventscribe.net/2022/AATOD/

Buprenorphine reduces methamphetamine intake and drug seeking behavior via activating nociceptin/orphanin FQ peptide receptor in rats.

Buprenorphine, which has been approved for the treatment of opioid dependence, reduces cocaine consumption by co-activating μ-opioid receptors and nociceptin/orphanin FQ peptide (NOP) receptors. However, the role of buprenorphine in methamphetamine (METH) reinforcement and drug-seeking behavior remains unclear. This study investigated the effects of buprenorphine on METH self-administration and reinstatement of METH-seeking behavior in rats. We found that buprenorphine pretreatment had an inhibitory effect on METH self-administration behavior, and that buprenorphine at a dose of 0.3 mg/kg could inhibit motivation to respond for METH. Pretreatment with the NOP receptor antagonist thienorphine (0.5 mg/kg) or SB-612111 (1 mg/kg) could reverse the inhibitory effect of buprenorphine (0.1 mg/kg) on the METH self-administration. Moreover, treatment with buprenorphine (0.1 mg/kg and 0.3 mg/kg) significantly reduced the drug-seeking behavior induced by context or by METH priming but failed to reduce the drug-seeking behavior induced by conditional cues. Additionally, the NOP receptor antagonist SB-612111 reversed the inhibitory action of buprenorphine on the drug-seeking behavior induced by METH priming. The results demonstrated that buprenorphine reduced either METH intake or the drug-seeking behavior by activating NOP receptors, providing empirical evidence for the clinical use of buprenorphine in the treatment of METH relapse and addiction.

Naltrexone Transport by a Proton-Coupled Organic Cation Antiporter in hCMEC/D3 Cells, an in Vitro Human Blood-Brain Barrier Model.

Naltrexone is a mu-opioid receptor antagonist used in the treatment of opioid and alcohol dependence. The blood-brain barrier (BBB) transport characteristics of naltrexone was investigated by means of hCMEC/D3 cells, a human immortalized brain capillary endothelial cell line. In hCMEC/D3 cells, naltrexone is taken up in a concentration-dependent manner. Furthermore, naltrexone uptake significantly decreased in the presence of H+/organic cation (OC) antiporter substrates, during the little alteration exhibited by substrates of well-identified OC transporters classified into SLC22A family. Although naltrexone uptake by hCMEC/D3 cells was partially affected by changes of ionic conditions, it was markedly decreased in the presence of the metabolic inhibitor sodium azide. Furthermore, when treated by ammonium chloride, naltrexone uptake by hCMEC/D3 cells was altered by intracellular acidification and alkalization, suggesting the involvement of oppositely directed proton gradient in naltrexone transport across the BBB. The results obtained in the present in vitro study suggest the active transport of naltrexone from blood to the brain across the BBB by the H+/OC antiporter.

A Comparative Study to Assess the Mental Health Problems, Quality of Life, Work Ability and Social Adjustments Among OST and Non-OST Drug Users in Chandigarh

Introduction: Injectable drug use is a cause of disease burden and a contributor to blood-borne virus transmission and health-related problems. It is one of the serious problems of our country. The best suitable strategy of treatment for opioid dependence is ‘opioid substitution therapy’ (OST). It is beneficial for the injectable drug users (IDUs) in reduction in the behaviour of injecting and opioid use, which helps in reducing criminal activities, domestic violence, enhancing ties within the family and improving productivity. Objective: To assess the mental health problems, quality of life, work ability and social adjustability among OST and non-OST IDUs. Materials and Methods: The descriptive study was conducted among 100 male IDUs (50 in the OST group and 50 in the non-OST group), registered with the two selected non-governmental organizations (NGOs) of Chandigarh selected by using the consecutive sampling technique. The OST group was contacted during their visit to the centre for receiving the daily dose of OST, while the non-OST group was contacted during their visit to the NGO centres for getting fresh syringes in exchange with used syringes under the syringe exchange programme. The data were collected by interviewing the study subjects by using the interview schedule comprising of the (a) socio-demographic profile, (b) health problems, (c) substance-use-related problems scale, (d) work ability and social adjustability scale, (e) the depression, anxiety and stress scale-21 and (f) World Health Organization Quality-of-Life BREF (WHOQOL BREF) Scale. All the tools were standardized and available in the open domain. Results: The study subjects were in the age group of 18–58 years with the mean age of 27.52 ± 6.67 years. Significantly lesser problems in the OST group study participants related to health, occupation, finance, legal, family, marital and social status were reported than those in the non-OST group participants ( t-test, p &lt; 0.01). A significantly higher percentage of the study participants in the non-OST group had depression, anxiety and stress than that in the OST group. Quality of life of IDUs in the OST group was significantly better than that of IDUs in the non-OST group, as per the WHOQOL BREF Scale (Mann–Whitney U test, p &lt; 0.05). Conclusion: IDUs on OST therapy (OST group) were having lesser problems in the area of health (physical and mental), occupational, financial, legal, family, marital, social and better quality of life than those in the non-OST group.

Opioid agonist treatment for people who are dependent on pharmaceutical opioids.

There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence. We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment). We used standard Cochrane methods. We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms. There is very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.