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The International Journal on Drug Policy Feb 2022There has been a marked growth in methadone maintenance treatment (MMT) in Iran in the past two decades with positive health outcomes. We conducted a systematic review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There has been a marked growth in methadone maintenance treatment (MMT) in Iran in the past two decades with positive health outcomes. We conducted a systematic review of studies on the prevalence of non-prescribed methadone use, methadone use disorder, and methadone-related poisoning and mortality in Iran.
METHODS
We searched International and Iranian databases up to May 2020 and contacted relevant experts. The pooled proportions were estimated through random-effects model. Methadone-related adverse outcomes were evaluated over time.
RESULTS
Sixty-five studies were included. The pooled estimates of non-prescribed methadone use in the last 12-month were 2.7% (95%CI: 0.9-5.4) and 0.1% (95%CI: 0.03-0.2) in the male and female general population, respectively. Among people who use drugs, 8.4% reported daily non-prescribed use in 2018. Four heterogeneous studies in drug treatment centers reported the existence of treatment-seeking for methadone use disorder. Methadone was responsible for 10.4% (95%CI: 4.5-18.3) of cases of acute poisoning in adults and 16.0% (95%CI: 9.3-24.1) in children. Methadone was reported as a cause of death in 53.5% of substance-related deaths referred to the Legal Medicine Organization while being the only cause in 35.8% of all cases.
CONCLUSION
Non-prescribed use of methadone in the general population is much less than opiates and some other available prescription opioids, like tramadol. However, notwithstanding the large and successful MMT program in Iran, increasing trends in methadone-related poisoning and deaths pose serious public health concerns. There is an urgent need to explore these fatal and non-fatal poisoning cases and implement policies to curb the harms associated with methadone use.
Topics: Adult; Analgesics, Opioid; Child; Female; Humans; Iran; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Public Health
PubMed: 34826790
DOI: 10.1016/j.drugpo.2021.103529 -
BMJ Clinical Evidence Jul 2009Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three approaches to treating opioid dependence. Stabilisation... (Review)
Review
INTRODUCTION
Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three approaches to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final aim is relapse prevention.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimes.
Topics: Analgesics, Opioid; Buprenorphine; Evidence-Based Medicine; Heroin Dependence; Humans; Incidence; Methadone; Naltrexone; Opioid-Related Disorders
PubMed: 21696648
DOI: No ID Found -
SpringerPlus 2016Methadone is commonly administered for chronic pain relief and treatment of opioid dependence. Concurrent with its increased consumption, toxicities and fatalities have... (Review)
Review
BACKGROUND
Methadone is commonly administered for chronic pain relief and treatment of opioid dependence. Concurrent with its increased consumption, toxicities and fatalities have increased. One of the adverse effects of opioid analgesics, including methadone, is that of nephrotoxicity. Opioids can have an effect on renal function through several different mechanisms.
METHODS
We searched common bibliographical databases for the terms methadone, toxicity, poisoning, kidney, renal, and nephrotoxicity and summarize our findings in this review.
RESULTS
Methadone can have both direct and indirect effects on the kidney. These effects include rhabdomyolysis (leading to acute kidney injury), volumetric changes, renal lipidosis and amyloidosis, kidney growth during pregnancy, and kidney transplant rejection.
CONCLUSION
Improved understanding of the effects of methadone on kidney function can promote safer and more confident use of the drug.
PubMed: 28018795
DOI: 10.1186/s40064-016-3757-1 -
American Journal of Epidemiology Oct 2014Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal... (Comparative Study)
Comparative Study Meta-Analysis Review
Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.
Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Models, Statistical; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome
PubMed: 25150272
DOI: 10.1093/aje/kwu190 -
Health Technology Assessment... Mar 2007To assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of... (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid-dependent individuals.
DATA SOURCES
Major electronic databases were searched from inception to August 2005. Industry submissions to the National Institute for Health and Clinical Excellence were accessed.
REVIEW METHODS
The assessment of clinical effectiveness was based on a review of existing reviews plus an updated search for randomised controlled trials (RCTs). A decision tree with Monte Carlo simulation model was developed to assess the cost-effectiveness of BMT and MMT. Retention in treatment and opiate abuse parameters were sourced from the meta-analysis of RCTs directly comparing flexible MMT with flexible dose BMT. Utilities were derived from a panel representing a societal perspective.
RESULTS
Most of the included systematic reviews and RCTs were of moderate to good quality, and focused on short-term (up to 1-year follow-up) outcomes of retention in treatment and the level of opiate use (self-report or urinalysis). Most studies employed a trial design that compared a fixed-dose strategy (i.e. all individuals received a standard dose) of MMT or BMT and were conducted in predominantly young men who fulfilled criteria as opiate-dependent or heroin-dependent users, without significant co-morbidities. RCT meta-analyses have shown that a fixed dose of MMT or BMT has superior levels of retention in treatment and opiate use than placebo or no treatment, with higher fixed doses being more effective than lower fixed doses. There was evidence, primarily from non-randomised observational studies, that fixed-dose MMT reduces mortality, HIV risk behaviour and levels of crime compared with no therapy and one small RCT has shown the level of mortality with fixed-dose BMT to be significantly less than with placebo. Flexible dosing (i.e. individualised doses) of MMT and BMT is more reflective of real-world practice. Retention in treatment was superior for flexible MMT than flexible BMT dosing but there was no significant difference in opiate use. Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT. A pooled RCT analysis showed no significant difference in serious adverse events with MMT compared with BMT. Although treatment modifier evidence was limited, adjunct psychosocial and contingency interventions (e.g. financial incentives for opiate-free urine samples) appeared to enhance the effects of both MMT and BMT. Also, MMT and BMT appear to be similarly effective whether delivered in a primary care or outpatient clinic setting. Although most of the included economic evaluations were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspective and comparators required to make their results generalisable to the NHS context. One company (Schering-Plough) submitted cost-effectiveness evidence based on an economic model that had a 1-year time horizon and sourced data from a single RCT of flexible-dose MMT compared with flexible-dose BMT and utility values obtained from the literature; the results showed that for MMT vs no drug therapy, the incremental cost-effectiveness ratio (ICER) was pound 12,584/quality-adjusted life-year (QALY), for BMT versus no drug therapy, the ICER was pound 30,048/QALY and in a direct comparison, MMT was found to be slightly more effective and less costly than BMT. The assessment group model found for MMT versus no drug therapy that the ICER was pound 13,697/QALY, for BMT versus no drug therapy that the ICER was pound 26,429/QALY and, as with the industry model, in direct comparison, MMT was slightly more effective and less costly than BMT. When considering social costs, both MMT and BMT gave more health gain and were less costly than no drug treatment. These findings were robust to deterministic and probabilistic sensitivity analyses.
CONCLUSIONS
Both flexible-dose MMT and BMT are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the more recent experience of clinicians in the use of buprenorphine, the possible risk of higher mortality of MMT and individual opiate-dependent users' preferences. Future research should be directed towards the safety and effectiveness of MMT and BMT; potential safety concerns regarding methadone and buprenorphine, specifically mortality and key drug interactions; efficacy of substitution medications (in particular patient subgroups, such as within the criminal justice system, or within young people); and uncertainties in cost-effectiveness identified by current economic models.
Topics: Analgesics, Opioid; Buprenorphine; Cost-Benefit Analysis; Female; Heroin Dependence; Humans; Male; Methadone
PubMed: 17313907
DOI: 10.3310/hta11090 -
Health and Quality of Life Outcomes Nov 2020Opioids addiction and misuse are among the major problems in the world today. There have been several preliminary studies examining the effect of methadone on depression... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Opioids addiction and misuse are among the major problems in the world today. There have been several preliminary studies examining the effect of methadone on depression among addicts, however, these studies have reported inconsistent and even contradictory results. Therefore, the aim of the present study was to determine the effect of methadone on depression in addicts in Iran and around the world, using a meta-analysis approach.
METHODS
This study was a systematic review and meta-analysis including articles published in the SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed and Web of Science databases were searched systematically to find articles published from 2006 to March 2019. Heterogeneity index was determined using the Cochran's test (Qc) and I. Considering heterogeneity of studies, the random effects model was used to estimate the standardized difference of mean score for depression. Subsequently, the level of depression reduction in Iran and worldwide in the intervention group before and after the testwas measured.
RESULTS
A total of 19 articles met the inclusion criteria, and were therefore selected for this systematic review and meta-analysis. The sample size of the intervention group in the selected studies was 1948. According to the meta-analysis results, the mean depression score in the intervention group was 26.4 ± 5.6 and 18.4 ± 2.6 before and after intervention respectively, indicating the reducing effect of methadone on depression, and this difference was statistically significant (P < 0.01).
CONCLUSION
The results of the present study show that methadone significantly reduces depression in addicts. Therefore, regular methadone use can be part of a drug treatment plan.
Topics: Depression; Humans; Iran; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 33225933
DOI: 10.1186/s12955-020-01599-3 -
Addiction & Health Jan 2018This comprehensive systematic review and meta-analysis were performed to assess the associated factors of maintenance in patients with methadone therapy in the world. (Review)
Review
BACKGROUND
This comprehensive systematic review and meta-analysis were performed to assess the associated factors of maintenance in patients with methadone therapy in the world.
METHODS
A systematic literature review was performed from several scientific databases; these include PubMed, Scopus, ISI Web of Science, and MEDLINE. We searched the following keywords: "Methadone", "Maintenance", "Retention", "Meta-analysis" and "Associated factors". Data were selected based on the inclusion and exclusion criteria. The purpose of this study was to assess the associated factors of maintenance in patients under treatment with methadone by an overall effect size, odds ratio (OR) [95% confidence interval (CI)] using meta-analysis.
FINDINGS
We selected 24 researches out of 94413 for our study based on the inclusion and exclusion criteria for systematic review and meta-analysis. The pooled recognized five significant positive associations of age, marital status, employment status, gender, and length of treatment with methadone usage (OR age = 3.566, 95% CI = 3.296-3.836, P < 0.001; OR marital status = 1.101, 95% CI = 1.028-1.175, P = 0.025; OR employment = 1.157, 95% CI = 1.060-1.254, P = 0.015; OR gender = 4.686, 95% CI = 4.434-4.939, P < 0.001; OR duration of treatment = 1.543, 95% CI = 1.443-1.647, P < 0.001; respectively). However, education and injection status showed a non-significant positive association with methadone usage (OR education level = 1.279, 95% CI = 0.976-1.583, P = 0.266; OR injection status = 1.205, 95% CI = 0.725-1.658, P = 0.442).
CONCLUSION
This systematic-review and meta-analysis study displayed that factors such as age, marital and employment status, gender, and duration of treatment are effective on maintenance in patients under treatment of methadone.
PubMed: 30627384
DOI: 10.22122/ahj.v10i1.488 -
Drug and Alcohol Dependence May 2023Methadone maintenance therapy is a leading treatment strategy for stabilizing and rehabilitating patients with opioid dependence; however, findings related to the risk... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Methadone maintenance therapy is a leading treatment strategy for stabilizing and rehabilitating patients with opioid dependence; however, findings related to the risk of motor vehicle collisions after methadone use have been conflicting. In the present study, we compiled the available evidence on the risk of motor vehicle collisions after methadone use.
METHODS
We completed a systematic review and meta-analysis of studies identified on six databases. Two reviewers independently screened the identified epidemiological studies, extracted data, and used the Newcastle-Ottawa Scale to assess the quality of the studies. Risk ratios were retrieved for analysis, conducted using random-effects model. Sensitivity analyses, subgroup analyses, and tests for publication bias were conducted.
RESULTS
Among 1446 identified relevant studies, a total of 7 epidemiological studies enrolling 33226142 participants met the inclusion criteria. Overall, study participants with methadone use had a higher risk of motor vehicle collisions than did those without methadone use (pooled relative risk 1.92, 95% CI 1.25-2.95; number needed to harm 11.3, 95% CI 5.3-41.6); the I statistic was 95.1%, indicating substantial heterogeneity. Subgroup analyses revealed that database type explained 95.36% of the between-study variance (p = 0.008). Egger's (p = 0.376) and Begg's (p = 0.293) tests revealed no evidence of publication bias. Sensitivity analyses indicated that the pooled results were robust.
CONCLUSION
The present review revealed that methadone use is significantly associated with a nearly doubled risk of motor vehicle collisions. Therefore, clinicians should exercise caution in implementing methadone maintenance therapy for drivers.
Topics: Humans; Methadone; Opioid-Related Disorders; Opiate Substitution Treatment; Accidents, Traffic; Motor Vehicles
PubMed: 36933540
DOI: 10.1016/j.drugalcdep.2023.109832 -
Current Drug Abuse Reviews 2016While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These... (Review)
Review
BACKGROUND
While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These discrepancies may be a direct result of variations in the measurement of chronic pain or definitions of response to methadone treatment. The goal of this study is to evaluate the association between pain and substance use behaviour to determine the real impact of comorbid pain in the methadone population. We also aim to examine sources of variation across the literature with a specific focus on the measurement of pain.
METHODS/DESIGN
We performed a systematic review using an electronic search strategy across CINAHL, MEDLINE, Web of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane Reviews and the Cochrane Central Register of Controlled Trials databases. Title, abstract, as well as full text screening and extraction were performed in duplicate. Studies evaluating the association between chronic pain and methadone maintenance treatment response were eligible for inclusion in this review. Using a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA) research collaborative, we assessed the reliability of patient self-reported pain and the validated Brief Pain Inventory (BPI) assessment tool.
RESULTS
After screening 826 articles we identified five studies eligible for full text extraction, of which three showed a significant relationship between the presence of pain and the increase in substance abuse among patients on methadone for the treatment of opioid dependence. Studies varied largely in the definitions and measurement of both pain and response to treatment. Results from our validation of pain measurement in the GENOA sample (n=297) showed the use of a simple self-reported pain question is highly correlated to the use of the BPI. Simply asking patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity, 84.4% PPV and 53.6% NPV to the BPI. The area under the ROC curve was 0.67 and the Pearson χ(2) was 37.3; (p<0.0001).
DISCUSSION
The field of addiction medicine is at a lack of consensus as to the real effect of chronic pain on treatment response among opioid dependent patients. Whether it be the lack of a single "gold standard" measurement of response, or a lack of consistent measurement of pain, it is difficult to summarize and compare the results of these relatively small investigations. In comparison to the BPI, use of the simple self-reported pain has lower sensitivity for identifying patients with pain, suggesting the inconsistencies in these studies may result from differences in pain measurement. Future validation studies of pain measurement are required to address the predictive value of self-reported pain.
Topics: Analgesics, Opioid; Chronic Pain; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Measurement
PubMed: 27021147
DOI: 10.2174/187447370901160321102837 -
PloS One 2013Methadone maintenance treatment (MMT) has been scaled up by the Chinese government alongside persistent compulsory drug user detention, but the extent to which detention... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methadone maintenance treatment (MMT) has been scaled up by the Chinese government alongside persistent compulsory drug user detention, but the extent to which detention interferes with MMT is unknown. The study systematically reviews Chinese MMT retention rates, reasons for drop out, and behavioural changes.
METHOD
Chinese and English databases of literature are searched for studies reporting retention rates, drug use and sexual behaviours among MMT participants in China between 2004 and 2013. The estimates are summarized through a systematic review and meta-analysis.
RESULTS
A total of 74 studies representing 43,263 individuals are included in this analysis. About a third of MMT participants drop out during the first three months of treatment (retention rate 69.0% (95% CI 57.7-78.4%)). Police arrest and detention in compulsory rehabilitation was the most common cause of drop out, accounting for 22.2% of all those not retained. Among retained participants, changing unsafe drug use behaviours was more effective than changing unsafe sexual behaviours. At 12 months following MMT initiation, 24.6% (15.7-33.5%) of MMT participants had a positive urine test, 9.3% (4.7-17.8%) injected drugs and only 1.1% (0.4-3.0%) sold sex for drugs. These correspond to 0.002 (<0.001-0.011), 0.045 (0.004-0.114) and 0.209 (0.076-0.580) times lower odds than baseline. However, MMT participants did not have substantial changes in condom use rates.
CONCLUSION
MMT is effective in drug users in China but participant retention is poor, substantially related to compulsory detention. Reforming the compulsory drug user detention system may improve MMT retention and effectiveness.
Topics: Behavior; China; Humans; Maintenance Chemotherapy; Methadone; Opiate Substitution Treatment; Patient Dropouts; Patient Participation; Publication Bias; Sexual Behavior
PubMed: 23922668
DOI: 10.1371/journal.pone.0068906