Harm reduction behaviors are associated with carrying naloxone among patients on methadone treatment.

BACKGROUND: Despite the widespread availability of naloxone, US opioid overdose rates continue to rise. The "Cascade of Care" (CoC) is a public health approach that identifies steps in achieving specific outcomes and has been used to identify gaps in naloxone carriage among individuals with opioid use disorder (OUD). We sought to apply this framework to a treatment-seeking population with OUD that may be more inclined to engage in harm reduction behaviors. METHODS: Patients were recruited from an urban methadone program to complete a survey. We assessed naloxone familiarity, availability, obtainability, training, and possession, as well as naloxone carriage rates, demographics, and harm reduction behaviors. A multivariable logistic regression examined associations between naloxone carriage and individual-level factors. RESULTS: Participants (n = 97) were majority male (59%), with a mean age of 48 (SD = 12), 27% had college education or higher, 64% indicated injection drug use, and 84% reported past naloxone training. All participants endorsed familiarity with naloxone, but only 42% regularly carried naloxone. The following variables were associated with carrying naloxone: White race (aOR = 2.94, 95% CI 1.02-8.52), college education (aOR = 8.11, 95% CI 1.76-37.47), and total number of self-reported harm reduction behaviors (aOR = 1.45, 95% CI 1.00-2.11). CONCLUSION: We found low rates of naloxone carriage among methadone-treated patients. Methadone programs provide opportunities for naloxone interventions and should target racial/ethnic minorities and individuals with lower education. The spectrum of harm reduction behaviors should be encouraged among these populations to enhance naloxone carriage.

Treatment Experiences for Patients Receiving Buprenorphine/Naloxone for Opioid Use Disorder: A Qualitative Study of Patients' Perceptions and Attitudes.

Background: Although buprenorphine/naloxone has been demonstrated to be an effective treatment for patients with opioid use disorder (OUD), treatment retention has been a challenge. This study extends what is presently a limited literature regarding patients' experiences with this medication and the implications for treatment retention. Methods: The study was conducted as a qualitative investigation of patients in treatment for OUD at the time of the study. Forty-three patients (27 men, 15 women, mean age 34.7) were recruited from three clinical settings, a community health center, an academically-based treatment site, and an independent substance abuse treatment facility. Most patients had returned to use in the past after attempts to become abstinent. Results: Patients generally reported positive experiences with this medication noting it helped to reduce opioid cravings quickly. As important considerations for treatment retention, patients emphasized a firm commitment to achieving abstinence when beginning treatment and a prescriber who is informed about and attentive to their emotional state. Diverging attitudes did exist regarding treatment duration as some patients were accepting of long-term treatment while others desired a relatively brief option. Among patients who had returned to use, potentially important issues emerged pertaining to the absence of patient outreach for missed medication appointments and inadequate discharge planning following stays at rehabilitation facilities. Conclusions: While results regarding the importance of patient motivation and strong patient-prescriber relationships have been noted in previous studies, other findings regarding opportunities to improve patient outreach and coordination of care have received relatively less attention and warrant further consideration.

[Buprenorphine depot in opiate use disorder]. / Buprenorfinedepot bij een stoornis in het gebruik van opiaten.

BACKGROUND: Patients with opiate use disorder may be treated medicamentally with methadone and sublingual buprenorphine. However, also two forms of subcutaneous buprenorphine that can be administered weekly or monthly are available. AIM: To describe the effectiveness and the side effects of the buprenorphine depot. METHOD: Embase was searched and cross-references were sought in the included studies and previous reviews. RESULTS: Nine articles were included. One randomized study (n = 428) compared buprenorphine depot to the sublingual form, with the depot being more effective after 12-24 weeks. The other randomized study (n = 504) compared the depot with placebo. The depot was found to be effective. In two comparative non-blinded studies, no significant difference in abstinence was reported between the depot and sublingual administration. Medium-term effectiveness (16-52 weeks) was confirmed in five follow-up studies, in which the depot preparation proved both effective and well tolerated. CONCLUSION: The buprenorphine depot is described as promising in the international literature. However, there are still several uncertainties that make its prescription should be done with great caution.

Continuity of opioid substitution treatment between prison and community in Southeast Asia: A scoping review.

BACKGROUND: Criminalisation of drug use and compulsory detention has largely characterised the Southeast Asia region's response to people who use drugs. Whilst access to and provision of healthcare for people living in prison are mandated by international human rights standards, many opioid dependent people living in prison continue to lack access to opioid substitution treatment (OST) during incarceration, and face uncertainties of continuity of care beyond the prison gate. METHODS: A scoping review using Arksey and O'Malley's framework mapped what is currently known about the continuity of OST post-release in Southeast Asia, with a focus on the three countries (Indonesia, Malaysia, Vietnam) that provide OST in at least one prison. A multi-lingual systematic search (English, Malay, Indonesian, Vietnamese) on Medline, CINAHL, Scopus, Web of Science, PsycINFO and the Cochrane Library collected and reviewed extant relevant published empirical and grey literature including government reports between 2011 and 2021. Of the 365 records found, 18 were eligible for inclusion following removal of duplicates and application of exclusion criteria. These records were charted and thematically analysed. RESULTS: Three main themes were generated: Facilitators of post release continuity of care, Barriers to post release continuity of care and Therapeutic considerations supporting post release continuity of care. When individual and structural gaps exist, disruptions to continuity of OST care post release are observed. Adequate methadone dosage of >80mg/day appears significantly associated with retention in post-release OST. CONCLUSIONS: The review highlights the facilitators, barriers and therapeutic considerations of continuity of care of OST between prison and community for people living in prisons from Indonesia, Malaysia and Vietnam. Improving community services with family support are key to supporting continued OST adherence post release along with reducing societal stigma towards people who use drugs and those entering or leaving prison. Further efforts are warranted to ensure parity, quality and continuity of OST care post release.

Transferring patients from high-dose methadone to buprenorphine: A retrospective case series.

OBJECTIVE: Transferring from methadone to buprenorphine can be difficult, -particularly at higher methadone doses. Precipitated withdrawal (PW) and severe opioid withdrawal can compromise transfers and limited data guide high-dose transfers. This study describes processes and outcomes of transfers to buprenorphine from methadone. DESIGN: A retrospective case series of transfers from methadone to buprenorphine. SETTING: Two elective, voluntary, specialized in-patient drug and alcohol facilities in Sydney, New South Wales, Australia. PARTICIPANTS: All admissions between July 1, 2015 and April 30, 2019 were screened using routinely collected coding data. The medical record was reviewed to identify subjects meeting the inclusion criteria of daily methadone use for at least 1 month, age > 18, and a treatment plan that included transfer from methadone to buprenorphine. Data were extracted on methadone dose, transfer medications, time to buprenorphine initiation, and transfer outcome. INTERVENTIONS: Subjects were transferred via two methods: morphine bridged and nonbridged. MAIN OUTCOME MEASURE: The primary outcome measure was successful transition to buprenorphine. RESULTS: Seventy-one subjects met inclusion criteria, of whom 62 initiated buprenorphine and 53 discharged on buprenorphine. Longer delay to buprenorphine initiation was seen with higher methadone doses. The highest daily methadone dose in subjects completing transfer was 180 mg. Outcomes with morphine bridging, using a steady state methadone: morphine ratio of 1:4, were similar to direct transfer. Only one subject discontinued buprenorphine because of PW. CONCLUSIONS: Transfer from high doses of methadone to buprenorphine can be achieved with high success rates in the in-patient setting.

Exploring the experiences of clients receiving opioid use disorder treatment at a methadone clinic in Kenya: a qualitative study.

BACKGROUND: Assessing the experiences of individuals on methadone treatment is essential to help evaluate the treatment program's effectiveness. This study aimed to explore the experiences of patients receiving methadone treatment at a clinic in Nairobi, Kenya. METHOD: This study employed an exploratory qualitative study design. Through purposive sampling, participants were enrolled from individuals attending a methadone clinic for at least 2 years. Semi-structured individual interviews were used to collect data on substance use and experience before methadone treatment and experiences after starting methadone treatment, including benefits and challenges. Interviews were transcribed, and NVIVO 12 software was used to code the data using the preidentified analytical framework. Thematic analyses were utilized to identify cross-cutting themes between these two data sets. Seventeen participants were enrolled. RESULTS: Seventeen participants were enrolled comprising 70% males, with age range from 23 to 49 years and more than half had secondary education. The interview data analysis identified four themes, namely: (a) the impact of opioid use before starting treatment which included adverse effects on health, legal problems and family dysfunction; (b) learning about methadone treatment whereby the majority were referred from community linkage programs, family and friends; (c) experiences with care at the methadone treatment clinic which included benefits such as improved health, family reintegration and stigma reduction; and (d) barriers to optimal methadone treatment such as financial constraints. CONCLUSION: The findings of this study show that clients started methadone treatment due to the devastating impact of opioid use disorder on their lives. Methadone treatment allowed them to regain their lives from the adverse effects of opioid use disorder. Additionally, challenges such as financial constraints while accessing treatment were reported. These findings can help inform policies to improve the impact of methadone treatment.

Impact of prerelease methadone on mortality among people with HIV and opioid use disorder after prison release: results from a randomized and participant choice open-label trial in Malaysia.

INTRODUCTION: Mortality is elevated after prison release and may be higher in people with HIV and opioid use disorder (OUD). Maintenance with opioid agonist therapy (OAT) like methadone or buprenorphine reduces mortality in people with OUD and may confer benefits to people with OUD and HIV leaving prison. Survival benefits of OAT, however, have not been evaluated prospectively in people with OUD and HIV leaving prison. METHODS: This study prospectively evaluated mortality after prison release and whether methadone initiated before release increased survival after release in a sample of men with HIV and OUD (n = 291). We linked national death records to data from a controlled trial of prerelease methadone initiation conducted from 2010 to 2014 with men with HIV and OUD imprisoned in Malaysia. Vital statistics were collected through 2015. Allocation to prerelease methadone was by randomization (n = 64) and participant choice (n = 246). Cox proportional hazards models were used to estimate treatment effects of prerelease methadone on postrelease survival. RESULTS: Overall, 62 deaths occurred over 872.5 person-years (PY) of postrelease follow-up, a crude mortality rate of 71.1 deaths per 1000 PY (95% confidence interval [CI] 54.5-89.4). Most deaths were of infectious etiology, mostly related to HIV. In a modified intention-to-treat analysis, the impact of prerelease methadone on postrelease mortality was consistent with a null effect in unadjusted (hazard ratio [HR] 1.3, 95% CI 0.6-3.1) and covariate-adjusted (HR 1.2, 95% CI 0.5-2.8) models. Predictors of mortality were educational level (HR 1.4, 95% CI 1.0-1.8), pre-incarceration alcohol use (HR 2.0, 95% CI 1.1-3.9), and lower CD4+ T-lymphocyte count (HR 0.8 per 100-cell/mL increase, 95% CI 0.7-1.0). CONCLUSIONS: Postrelease mortality in this sample of men with HIV and OUD was extraordinarily high, and most deaths were likely of infectious etiology. No effect of prerelease methadone on postrelease mortality was observed, which may be due to study limitations or an epidemiological context in which inadequately treated HIV, and not inadequately treated OUD, is the main cause of death after prison release. TRIAL REGISTRATION: NCT02396979. Retrospectively registered 24/03/2015.

Interest without uptake: A mixed-methods analysis of methadone utilization in Kyrgyz prisons.

HIV incidence continues to increase in Eastern Europe and Central Asia (EECA), in large part due to non-sterile injection drug use, especially within prisons. Therefore, medication-assisted therapy with opioid agonists is an evidence-based HIV-prevention strategy. The Kyrgyz Republic offers methadone within its prison system, but uptake remains low. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a framework for identifying people who would potentially benefit from methadone, intervening to identify OUD as a problem and methadone as a potential solution, and providing referral to methadone treatment. Using an SBIRT framework, we screened for OUD in Kyrgyz prisons among people who were within six months of returning to the community (n = 1118). We enrolled 125 people with OUD in this study, 102 of whom were not already engaged in methadone treatment. We conducted a pre-release survey followed by a brief intervention (BI) to address barriers to methadone engagement. Follow-up surveys immediately after the intervention and at 1 month, 3 months, and 6 months after prison release assessed methadone attitudes and uptake. In-depth qualitative interviews with 12 participants explored factors influencing methadone utilization during and after incarceration. Nearly all participants indicated favorable attitudes toward methadone both before and after intervention in surveys; however, interest in initiating methadone treatment remained very low both before and after the BI. Qualitative findings identified five factors that negatively influence methadone uptake, despite expressed positive attitudes toward methadone: (1) interpersonal relationships, (2) interactions with the criminal justice system, (3) logistical concerns, (4) criminal subculture, and (5) health-related concerns.

Discussion on methadone initiation protocols: A case report.

Through a concrete case, we discuss the main published protocols to initiate methadone and illustrate the advantages and disadvantages of rapid or gradual initiation and on-demand or fixed doses with rescue doses. Daily doses can vary widely depending on the protocol chosen. An on-demand administration could lead to an overdose as illustrated in our case. A better understanding of particularities and limitations of these protocols could lead to safer methadone initiation. Systematic comparison of different protocols and calculation of the daily dose should be a standard in clinical practice.

Acceptability, feasibility, and outcomes of a clinical pilot program for video observation of methadone take-home dosing during the COVID-19 pandemic.

BACKGROUND: Methadone is one of the most utilized treatments for opioid use disorder. However, requirements for observing methadone dosing can impose barriers to patients and increase risk for respiratory illness transmission (e.g., COVID-19). Video observation of methadone dosing at home could allow opioid treatment programs (OTPs) to offer more take-home doses while ensuring patient safety through remote observation of ingestion. METHODS: Between April and August 2020, a clinical pilot program of video observation of methadone take-home dosing via smartphone was conducted within a multisite OTP agency. Participating patients completed a COVID-19 symptom screener and submitted video recordings of themselves ingesting all methadone take-home doses. Patients who followed these procedures for a two-week trial period could continue participating in the full pilot program and potentially receive more take-home doses. This retrospective observational study characterizes patient engagement and compares clinical outcomes with matched controls. RESULTS: Of 44 patients who initiated the two-week trial, 33 (75 %) were successful and continued participating in the full pilot program. Twenty full pilot participants (61 %) received increased take-home doses. Full pilot participants had more days with observed dosing over a 60-day period than matched controls (mean = 53.2 vs. 16.6 days, respectively). Clinical outcomes were similar between pilot participants and matched controls. CONCLUSIONS: Video observation of methadone take-home dosing implemented during the COVID-19 pandemic was feasible. This model has the potential to enhance safety by increasing rates of observed methadone dosing and reducing infection risks and barriers associated with relying solely on face-to-face observation of methadone dosing.

Inter-trial variability in postural control and brain activation: Effects of previous opiate abuse.

There is an abundant literature demonstrating the superiority of inter-trial variability (ITV) of reaction time over mean reaction time in the early identification of subtle cognitive processing decrements. The present study extends these ideas by examining brain activation and postural control ITV among participants with versus without a history of chronic opiate abuse. Participants enrolled in opiate abuse (n = 82) and control (n = 112) groups completed tasks that challenged selective attention and balance. During the respective tasks, the inter-trial variabilities in frontal P300a electroencephalographic responses and sway strategy scores outperformed their mean levels in differentiating the groups. The relevance of several potential alternative explanations for the differences, including premorbid conduct disorder and comorbid alcohol abuse, depression, and methadone use, was discounted via simultaneous or post hoc analyses. It appears that chronic opiate abuse has adverse CNS effects that persist into the protracted abstinence period. These effects alter the temporal stability of its response to external and internal stimuli.

Buprenorphine & methadone dosing strategies to reduce risk of relapse in the treatment of opioid use disorder.

BACKGROUND: Although there is consensus that having a "high-enough" dose of buprenorphine (BUP-NX) or methadone is important for reducing relapse to opioid use, there is debate about what this dose is and how it should be attained. We estimated the extent to which different dosing strategies would affect risk of relapse over 12 weeks of treatment, separately for BUP-NX and methadone. METHODS: This was a secondary analysis of three comparative effectiveness trials. We examined four dosing strategies: 1) increasing dose in response to participant-specific opioid use, 2) increasing dose weekly until some minimum dose (16 mg BUP, 100 mg methadone) was reached, 3) increasing dose weekly until some minimum and increasing dose in response to opioid use thereafter (referred to as the "hybrid strategy"), and 4) keeping dose constant after the first 2 weeks of treatment. We used a longitudinal sequentially doubly robust estimator to estimate contrasts between dosing strategies on risk of relapse. RESULTS: For BUP-NX, increasing dose following the hybrid strategy resulted in the lowest risk of relapse. For methadone, holding dose constant resulted in greatest risk of relapse; the other three strategies performed similarly. For example, the hybrid strategy reduced week 12 relapse risk by 13 % (RR: 0.87, 95 %CI: 0.83-0.95) and by 20 % (RR: 0.80, 95 %CI: 0.71-0.90) for BUP-NX and methadone respectively, as compared to holding dose constant. CONCLUSIONS: Doses should be targeted toward minimum thresholds and, in the case of BUP-NX, raised when patients continue to use opioids.

Buprenorphine/naloxone and methadone effectiveness for reducing craving in individuals with prescription opioid use disorder: Exploratory results from an open-label, pragmatic randomized controlled trial.

BACKGROUND: Craving reduction is an important target in the treatment of prescription-type opioid use disorder (POUD). In this exploratory analysis, we compared the effectiveness of BUP/NX flexible model of care relative to methadone for craving reduction in individuals with POUD. METHODS: We analyzed data from a multicentric, pragmatic, 24-week open-label randomized controlled trial conducted in participants with POUD (N = 272) who were randomly assigned to BUP/NX model of care with flexible take-home dosing (n = 138) or the standard model of care with closely supervised methadone (n = 134). Treatments were prescribed and administered according to local guidelines, in diverse clinical settings. Craving was measured using the Brief Substance Craving Scale at baseline, week 2, 6, 10, 14, 18 and 22. RESULTS: Cravings decreased in both treatment groups over 22 weeks (BUP/NX adjusted mean difference = -5.52, 95% CI = -6.91 to -4.13; methadone adjusted mean difference = -3.95, 95% CI = -5.28 to -2.63; p < 0.001), and were overall lower in the BUP/NX group (adjusted mean = 4.04, 95% CI = 3.43-4.64) than the methadone group (adjusted mean = 5.13, 95% CI = 4.51-5.74; p < 0.001). The time by treatment group interaction (favoring BUP/NX) was statistically significant at week 2 (adjusted mean difference = -1.58, 95% CI = -3.13 to -0.03; p = 0.041). CONCLUSIONS: Compared to the standard methadone model of care, flexible take-home dosing of BUP/NX was associated with lower craving in individuals with POUD. These findings can contribute to guiding shared decision-making regarding OAT treatment in this population.

Maintenance on extended-release naltrexone is associated with reduced injection opioid use among justice-involved persons with opioid use disorder.

INTRODUCTION: Opioid use disorder (OUD) and injection drug use (IDU) place justice-involved individuals at increased risk for acquiring or transmitting HIV or hepatitis C virus (HCV). Methadone and buprenorphine have been associated with reduced opioid IDU; however, the effect of extended-release naltrexone (XR-NTX) on this behavior is incompletely studied. METHODS: This study examined injection opioid use and shared injection equipment behavior from a completed double-blind placebo-controlled trial of XR-NTX among 88 justice-involved participants with HIV and OUD. Changes in participants' self-reported daily injection opioid use and shared injection equipment was evaluated pre-incarceration, during incarceration, and monthly post-release for 6 months. The study also assessed differences in time to first opioid injection post-release. The research team performed intention to treat and "as treated" (high treatment versus low treatment) analyses. RESULTS: Fifty-eight of 88 participants (69.5 %) endorsed IDU and 26 (29.5 %) reported sharing injection equipment in the 30 days pre-incarceration; 2 participants (2.2 %) reported IDU during incarceration; 19 (21.6 %) reported IDU one month post-release from prison or jail. Fifty-four (61.4 %) participants had an HIV RNA below 200 copies/mL and 62 (70.5 %) were baseline HCV antibody positive. The 6-month follow-up rate was 49.5 % and 50.5 % for those who received XR-NTX and placebo, respectively, which was not significantly different (p = 0.822). Participants in the XR-NTX and placebo groups had similar low mean opioid injection use post-release and time to first injection opioid use in the Intention-to-treat analysis. In the as-treated analysis, participants in the high treatment group had significantly lower mean proportion of days injecting opioids (13.8 % high treatment versus 22.8 % low treatment, p = 0.02) by month 1, which persisted up to 5 months post-release (0 % high treatment vs 24.3 % low treatment, p < 0.001) and experienced a longer time to first opioid injection post-release (143.8 days high treatment vs 67.4 days low treatment, p < 0.001). CONCLUSIONS: Injection opioid use was low during incarceration and remained low post-release in this justice-involved population. Retention on XR-NTX was associated with reduced intravenous opioid use, which has important implications for reducing transmission of HIV and HCV.

Improving geographic access to methadone clinics.

INTRODUCTION: Opioid misuse is a nationwide public health crisis. Methadone treatment is proven to be highly successful in preventing opioid use disorder, reducing the use of illicit drugs, and preventing overdoses. Clients acquire methadone daily from clinics, making geographic access crucial for the initiation of and adherence to treatment. METHODS: This work estimates unsatisfied methadone demand due to lack of geographic access at a census tract level and models the problem of identifying optimal locations to open new methadone clinics. The objective function of the model is a weighted combination of providing access to individuals with unmet methadone demand and improving the travel time of individuals currently attending a clinic. Data on existing methadone clinics and statewide methadone demand is acquired from Substance Abuse and Mental Health Services Administration (SAMHSA) surveys from 2019. Unsatisfied demand is estimated through a linear regression model after aggregating the population, heroin use, and satisfied methadone demand at the state level. RESULTS: Nationwide, we find 18.2 % of the United States population does not have geographic access to a methadone clinic and estimate 77,973 individuals in these areas would attend a clinic if geographic access barriers were removed (95 % CI: 67,413-88,532). In a case study of six Midwestern states, we find that geography significantly contributes to the value of opening additional clinics and we see large differences in expected gains between states sharing similar characteristics such as population and satisfied methadone demand. The number of additional clients served by opening one new clinic ranges from 180 to 804 across these six states, representing between 8.4 % and 16.2 % of state unmet demand. Between 1.2 % and 14.1 % of existing clients were reassigned with a single newly opened clinic, with a one-way average travel distance improvement between 6.3 and 11.9 miles / person / day for these clients. CONCLUSIONS: The results demonstrate the large unserved methadone demand in the United States, the significant improvement in methadone access for new and existing clients that can be achieved by opening new clinics, and the important role state-specific geography plays in these decisions.

Cumulative barriers to retention in methadone treatment among adults from rural and small urban communities.

BACKGROUND: Though methadone has been shown to effectively treat opioid use disorder, many barriers prevent individuals from accessing and maintaining treatment. Barriers are prevalent in less populated areas where treatment options are limited. This study examines barriers to retention in methadone treatment in a small Midwest community and identifies factors associated with greater endorsement of barriers. METHODS: Patients at an opioid treatment program (N = 267) were recruited to complete a computer-based survey onsite. Surveys assessed demographics, opioid misuse, depression and anxiety symptoms, trauma history and symptoms, social support, and barriers to retention in treatment (e.g., childcare, work, housing, transportation, legal obligations, cost, health). Descriptive statistics were used to examine individual barriers and multiple regression was calculated to identify demographic and psychosocial factors associated with greater cumulative barriers. RESULTS: Most participants reported at least one barrier to retention in treatment and more than half reported multiple barriers. Travel hardships and work conflicts were the most highly endorsed barriers. Past year return to use (B = 2.31, p = 0.004) and more severe mental health symptomology (B = 0.20, p = 0.038) were associated with greater cumulative barriers. Greater levels of social support were associated with fewer barriers (B = - 0.23, p < 0.001). CONCLUSION: This study adds to the limited research on barriers to retention in methadone treatment among patients in rural and small urban communities. Findings suggest flexible regulations for dispensing methadone, co-location or care coordination, and family or peer support programs may further reduce opioid use and related harms in small communities. Individuals with past year return to use reported a greater number of barriers, highlighting the time following return to use as critical for wraparound services and support. Those with co-occurring mental health issues may be vulnerable to poor treatment outcomes, as evidenced by greater endorsement of barriers. As social support emerged as a protective factor, efforts to strengthen informal support networks should be explored as adjunctive services to methadone treatment.

Buprenorphine Compared with Methadone in Pregnancy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or buprenorphine is the optimal agent remains unclear. METHODS: We searched EMBASE, PubMed, Web of Science, Scopus, Open Gray, CINAHL and the Cochrane Central Registry of Controlled Trials (CENTRAL) from inception to April 2020 for randomized controlled trials (RCTs) and cohort studies comparing methadone and buprenorphine treatment for opioid-using mothers. Included studies assessed maternal and or neonatal outcomes. We used random-effects meta-analyses to estimate summary measures for outcomes and report these separately for RCTs and cohort studies. RESULTS: Of 408 abstracts screened, 20 papers were included (4 RCTs, 16 cohort, 223 and 7028 participants respectively). All RCTs (4/4) had a high risk of bias and median (IQR) Newcastle Ottawa Scale for cohort studies was 7.5 (6-9). In both RCTs and cohort studies, buprenorphine was associated with; greater offspring birth weight (weighted mean difference [WMD] 343 g (95% CI: 40-645 g) in RCT and 184 g (95% CI: 121-247 g) in cohort studies); body length at birth (WMD 2.28 cm (95% CI: 1.06-3.49 cm) in RCTs and 0.65 cm (95% CI: 0.31-0.98 cm) in cohort studies); and reduced risk of prematurity (risk ratio [RR] 0.41 (95% CI: 0.18-0.93) in RCTs and 0.63 [95% CI: 0.53-0.75] in cohort studies) when compared to methadone. All other clinical outcomes were comparable. CONCLUSIONS: Compared to methadone, buprenorphine was consistently associated with improved birthweight and gestational age, however given potential biases, results should be interpreted with caution.