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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 -
Pain Practice : the Official Journal of... Nov 2023Epidural analgesia is a common technique for managing perioperative and obstetric pain. Patients with cancer who cannot tolerate opioids or not responding to... (Review)
Review
BACKGROUND
Epidural analgesia is a common technique for managing perioperative and obstetric pain. Patients with cancer who cannot tolerate opioids or not responding to conventional treatment may benefit from epidural analgesia. Therefore, this systematic review aimed to analyze the efficacy and safety of epidural analgesia in patients with intractable cancer pain.
METHODS
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify studies on patients with cancer who received epidural analgesia. We assessed the quality of all included studies using the risk-of-bias tool or Newcastle-Ottawa scale. The primary outcome was pain relief after epidural analgesia, and the secondary outcome was quality of life, analgesic consumption, and adverse events. The studies were grouped based on the medications used for epidural analgesia. A descriptive synthesis was performed following the Synthesis Without Meta-analysis reporting guideline.
RESULTS
Our systematic review included nine randomized controlled trials (n = 340) and 15 observational studies (n = 926). Two randomized controlled trials suggested that epidural opioids were not superior to systemic opioids in relieving pain. Epidural opioids combined with local anesthetics or adjuvants, including calcitonin, clonidine, ketamine, neostigmine, methadone, and dexamethasone, offered better analgesic effects. No significant difference in pain relief between an intermittent bolus and a continuous infusion of epidural morphine was observed. Epidural opioids had more analgesic effects on nociceptive pain than neuropathic pain. The methods used to evaluate the quality of life and the corresponding results were heterogeneous among studies. Six observational studies demonstrated that some patients could have decreased opioid consumption after epidural analgesia. Adverse events, including complications and drug-related side effects, were reported in 23 studies. Five serious complications, such as epidural abscess and hematoma, required surgical management. The heterogeneity and methodological limitations of the studies hindered meta-analysis and evidence-level determination.
CONCLUSION
Coadministration of epidural opioids, local anesthetics, and adjuvants may provide better pain relief for intractable cancer pain. However, we must assess the patients to ensure that the benefits outweigh the risks before epidural analgesia. Therefore, further high-quality studies are required.
Topics: Female; Humans; Pregnancy; Analgesia, Epidural; Analgesics; Analgesics, Opioid; Anesthetics, Local; Cancer Pain; Neoplasms; Pain, Postoperative; Quality of Life
PubMed: 37455298
DOI: 10.1111/papr.13273 -
The Journal of Pain Mar 2021Adequate analgesia can be challenging, as pharmacological options are not necessarily effective for all types of pain and are associated with adverse effects. Methadone...
Adequate analgesia can be challenging, as pharmacological options are not necessarily effective for all types of pain and are associated with adverse effects. Methadone is increasingly being considered in the management of both cancer-related and noncancer-related pain. The purpose of this article is to provide a narrative review of all available randomized controlled trials (RCTs) investigating the effectiveness of methadone in the management of pain, in relation to a comparison drug. The primary outcome was analgesic effectiveness, and the secondary outcomes were side effects and cost. A search of PubMed, Medline, Embase, and Google Scholar databases was conducted to identify eligible RCTs and methodologic quality was assessed. A total of 40 RCTs were included in this review. The majority compared methadone to morphine or fentanyl. Analgesic effectiveness of methadone was demonstrated in different types of pain, including postprocedural, cancer-related, nociceptive, and neuropathic pain. The evidence demonstrates that the use of methadone in postprocedural pain and in cancer-related pain may be dependent on the procedure and cancer type, respectively. Side effects experienced were generally similar to the comparison drug, and lower cost was a benefit to using methadone. Methadone may also be useful as an adjunctive analgesic for adequate pain control, as well as in patients with renal impairment. Additional high-quality, large-scale RCT evidence is needed to establish its role as monotherapy or as an adjunctive medication. Future research should also aim to standardize reported outcomes for measuring analgesic effectiveness to permit for pooled analysis across studies. PERSPECTIVE: This article presents a systematic review, which includes a summary of published RCTs investigating the effectiveness of methadone in the management of pain. This is important for determining its analgesic utility and for identifying gaps in existing knowledge.
Topics: Analgesics, Opioid; Cancer Pain; Humans; Methadone; Neuralgia; Nociceptive Pain; Outcome Assessment, Health Care; Pain Management; Randomized Controlled Trials as Topic
PubMed: 32599153
DOI: 10.1016/j.jpain.2020.04.004 -
Drug and Alcohol Dependence Dec 2022Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions.
BACKGROUND
Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions.
AIM
Our aim was to publish an interactive summary of all peer-reviewed interventional and observational trials assessing the treatment of OUD and common clinical outcomes.
METHODS
PubMed, Embase, PsycInfo, Cochrane Central Register of Clinical Trials, and Web of Science were queried using multiple OUD-related MESH terms, without date limitations, for English-language publications. Inclusions were human subjects, treatment of OUD, OUD patient or community-level outcomes, and systematic reviews of OUD interventions. Exclusions were laboratory studies, reviews, and case reports. Two reviewers independently scanned abstracts for inclusion before coding eligible full-text articles by pre-specified filters: research design, study population, study setting, intervention, outcomes, sample size, study duration, geographical region, and funding sources.
RESULTS
The OUD Evidence Map (https://med.nyu.edu/research/lee-lab/research/opioid-use-disorder-treatment-evidence-map) identified and assessed 12,933 relevant abstracts through 2020. We excluded 9455 abstracts and full text reviewed 2839 manuscripts; 888 were excluded, 1591 were included in the final evidence map. The most studied OUD interventions were methadone (n = 754 studies), buprenorphine (n = 499), and naltrexone (n = 134). The most common outcomes were heroin/opioid use (n = 708), treatment retention (n = 557), and non-opioid drug use (n = 368). Clear gaps included a wider array of opioid agonists for treatment, digital behavioral interventions, studies of OUD treatments in criminal justice settings, and overdose as a clinical outcome.
CONCLUSION
This OUD Evidence Map highlights the importance of pharmacologic interventions for OUD and reductions in opioid use. Future iterations will update results annually and scan policy-level interventions.
Topics: Humans; Opiate Substitution Treatment; Analgesics, Opioid; Opioid-Related Disorders; Buprenorphine; Methadone; Naltrexone
PubMed: 36332588
DOI: 10.1016/j.drugalcdep.2022.109657 -
Value in Health : the Journal of the... Feb 2021The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare...
OBJECTIVES
The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare systems and society. Simulation models have been developed to capture and identify ways to manage this complexity and to evaluate the potential costs of different strategies to reduce overdoses and OUD. A review of simulation-based economic evaluations is warranted to fully characterize this set of literature.
METHODS
A systematic review of simulation-based economic evaluation (SBEE) studies in opioid research was initiated by searches in PubMed, EMBASE, and EbscoHOST. Extraction of a predefined set of items and a quality assessment were performed for each study.
RESULTS
The screening process resulted in 23 SBEE studies ranging by year of publication from 1999 to 2019. Methodological quality of the cost analyses was moderately high. The most frequently evaluated strategies were methadone and buprenorphine maintenance treatments; the only harm reduction strategy explored was naloxone distribution. These strategies were consistently found to be cost-effective, especially naloxone distribution and methadone maintenance. Prevention strategies were limited to abuse-deterrent opioid formulations. Less than half (39%) of analyses adopted a societal perspective in their estimation of costs and effects from an opioid-related intervention. Prevention strategies and studies' accounting for patient and physician preference, changing costs, or result stratification were largely ignored in these SBEEs.
CONCLUSION
The review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid agonist treatments and identifies major gaps for future research.
Topics: Analgesics, Opioid; Costs and Cost Analysis; Humans; Methadone; Models, Economic; Naloxone; Narcotic Antagonists; Opiate Overdose; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders
PubMed: 33518022
DOI: 10.1016/j.jval.2020.07.013 -
Addictive Behaviors Jan 2022There 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... (Meta-Analysis)
Meta-Analysis Review
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 (11 buprenorphine, six methadone, and two naltrexone). 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.
Topics: Analgesics, Opioid; Buprenorphine; Ethnicity; Female; Humans; Male; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; United States
PubMed: 34543869
DOI: 10.1016/j.addbeh.2021.107113 -
Addiction Science & Clinical Practice Nov 2021Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may... (Review)
Review
BACKGROUND
Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes.
OBJECTIVES
This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.
METHODS
Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively.
RESULTS
Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese.
LIMITATIONS
The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.
CONCLUSION
The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.
Topics: Buprenorphine; Calcium-Calmodulin-Dependent Protein Kinases; Eye Proteins; Genome-Wide Association Study; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Polymorphism, Single Nucleotide
PubMed: 34838141
DOI: 10.1186/s13722-021-00278-y -
Drug and Alcohol Dependence Aug 2021Opioid treatment programs (OTPs) may provide interim methadone services - up to 120 days of methadone dosing without counseling. Regulatory requirements limit use of...
BACKGROUND
Opioid treatment programs (OTPs) may provide interim methadone services - up to 120 days of methadone dosing without counseling. Regulatory requirements limit use of interim methadone services. We summarized the evidence on interim methadone and other strategies to minimize wait lists in OTPs.
METHODS
A scoping review selected studies of interim methadone and strategies that facilitated access to methadone. Randomized trials and controlled observational studies were prioritized; if evidence was lacking, lesser quality evidence was included.
RESULTS
Six studies examined interim methadone and three studies examined alternatives: low threshold services, an open access policy, and a medication first policy. The studies included four randomized clinical trials of interim methadone (with three follow-up reports and five secondary analyses), one prospective cohort of interim methadone, one retrospective cohort of interim methadone, one randomized trial of low threshold services and two pre-post assessments of changes in program or state policies. The clinical trials and observational cohorts reported reductions in heroin use during interim methadone and participants were more likely to enter OTPs than those on wait lists. Retention rates in interim methadone were similar to patients in active treatment. Studies testing strategies to facilitate access to methadone were effective without interim methadone's restrictions.
CONCLUSION
Interim methadone appears to be effective and safe compared to wait list controls and provided similar outcomes to standard services. Interim methadone could increase access to OTPs. More research is needed on the alternative approaches to facilitate access to medication with comparisons to wait list controls and assessment of patient outcomes.
Topics: Analgesics, Opioid; Humans; Methadone; Opioid-Related Disorders; Prospective Studies; Retrospective Studies; Waiting Lists
PubMed: 34051546
DOI: 10.1016/j.drugalcdep.2021.108766 -
Pain Medicine (Malden, Mass.) Dec 2021To investigate the effects of intraoperative methadone in comparison with those of standard-of-care intraoperative opioids, such as fentanyl and morphine, on pain...
OBJECTIVE
To investigate the effects of intraoperative methadone in comparison with those of standard-of-care intraoperative opioids, such as fentanyl and morphine, on pain scores, opioid consumption, and adverse effects in adults undergoing cardiothoracic surgery.
METHODS
The literature was reviewed in PubMed, Embase, Cochrane Library, and Google Scholar, followed by a manual search of the reference lists of the identified articles. Search terms included a combination of "intraoperative methadone," "methadone," and "cardiac surgery." Our review includes four studies published between 2011 and 2020. Quality assessment of the studies was performed.
RESULTS
The initial search identified 715 articles, from which 461 duplicates were removed and 236 were eliminated on the basis of inclusion and exclusion criteria. Eighteen articles underwent full-text review. Four studies evaluating a total of 435 patients with various cardiothoracic procedures were included in this review. We found that intraoperative methadone decreased acute postoperative pain and reduced postoperative opioid consumption in the first 24 postoperative hours in patients who received 0.1-0.3 mg/kg intraoperative methadone in comparison with morphine and fentanyl. No difference was found in adverse effects between the groups. Quality assessment of the studies showed a low risk of bias in three of the randomized controlled trials and a high risk of bias in the retrospective review because of the baseline confounding bias in the study design.
CONCLUSIONS
Intraoperative methadone use reduces acute postoperative pain and lowers opioid consumption in comparison with morphine and fentanyl. Initial results suggest that methadone may be an equivalent opioid to be administered during cardiothoracic procedures to reduce acute postsurgical pain, though further research is warranted.
Topics: Adult; Analgesics, Opioid; Cardiac Surgical Procedures; Humans; Methadone; Pain, Postoperative; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 34487175
DOI: 10.1093/pm/pnab269 -
Drugs Feb 2024Pain associated with cancer is a common feature among children and adolescents. Among opioids, methadone is a unique drug for its multiple mechanisms of action.... (Review)
Review
Pain associated with cancer is a common feature among children and adolescents. Among opioids, methadone is a unique drug for its multiple mechanisms of action. Methadone is currently underutilized in children. The use of methadone for cancer pain management in children was assessed in a systematic review. Altogether, 141 children receiving methadone were examined, and another 126 children were assessed for QT prolongation. In the clinical studies, modalities of use, dosing, and duration of assessment were highly variable. In general, methadone was effective and well tolerated with a limited tendency for dose increases. QT prolongation was reported in a percentage of patients independently of the dosages or other variables. The majority of studies considered the use of methadone to be safe and effective in children. Despite methadone possessing interesting properties that make this drug unique in a pediatric context, data is limited, and the literature available is based on retrospective studies. Methadone could be an effective, inexpensive, and versatile medication in children with cancer who have pain. This drug deserves more interest and should prompt studies of better quality with a larger number of patients.
Topics: Adolescent; Humans; Child; Methadone; Pain Management; Retrospective Studies; Analgesics, Opioid; Pain; Neoplasms; Long QT Syndrome
PubMed: 38324240
DOI: 10.1007/s40265-024-02001-y