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Drug and Alcohol Dependence Feb 2020Opioid abuse is a public health crisis. As opioid misuse worsens, efforts are being made to increase access to medication-assisted treatments. Methadone is a...
BACKGROUND
Opioid abuse is a public health crisis. As opioid misuse worsens, efforts are being made to increase access to medication-assisted treatments. Methadone is a medication-assisted treatment used to treat opioid dependence and chronic pain. While methadone is beneficial in the treatment of opiate abuse and chronic pain, side effects of the medication include hormonal and sexual function changes. The purpose of this report is to review the effects of methadone on the hypothalamic pituitary gonadal axis hormones and sexual functioning in males and females.
METHODS
A search of PubMed was conducted using pre-defined criteria, resulting in the evaluation of 295 articles. A total of 72 articles, including 52 human studies and 20 animal studies, met the selection criteria and were reviewed. The included studies examined the effects of methadone on the hypothalamic pituitary gonadal axis and/or sexual function.
RESULTS
There was evidence of methadone-induced hormonal changes, disruptions in the hypothalamic pituitary gonadal axis, and sexual dysfunction, although there was some variability in the results of the reviewed studies. Differences in methadone dose and length of exposure to treatment appears to influence the variability in the results. Much of the literature examines the effects of methadone in males, with very limited research examining the effects in females.
CONCLUSIONS
Despite its effectiveness for opiate abuse and chronic pain treatment, methadone has disruptive effects on the hypothalamic pituitary gonadal axis and sexual function. Further research is warranted to better define potential methadone-induced endocrine consequences and to further examine the effects of methadone in females.
Topics: Analgesics, Opioid; Animals; Chronic Pain; Female; Gonadal Disorders; Humans; Hypothalamo-Hypophyseal System; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Sexual Dysfunction, Physiological
PubMed: 31901578
DOI: 10.1016/j.drugalcdep.2019.107823 -
The Cochrane Database of Systematic... Nov 2020The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital delivery, a fourfold increase in opioid use is reported from 1999 to 2014 (Haight 2018). Heroin crosses the placenta, and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. This is an updated version of the original Cochrane Review first published in 2008 and last updated in 2013.
OBJECTIVES
To assess the effectiveness of any maintenance treatment alone or in combination with a psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions alone for child health status, neonatal mortality, retaining pregnant women in treatment, and reducing the use of substances.
SEARCH METHODS
We updated our searches of the following databases to February 2020: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
Randomised controlled trials which assessed the efficacy of any pharmacological maintenance treatment for opiate-dependent pregnant women.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high dropout rate (30% to 40%), and this was unbalanced between groups. Methadone versus buprenorphine: There was probably no evidence of a difference in the dropout rate from treatment (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.37 to 1.20, three studies, 223 participants, moderate-quality evidence). There may be no evidence of a difference in the use of primary substances between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.68, two studies, 151 participants, low-quality evidence). Birth weight may be higher in the buprenorphine group in the two trials that reported data MD;-530.00 g, 95%CI -662.78 to -397.22 (one study, 19 particpants) and MD: -215.00 g, 95%CI -238.93 to -191.07 (one study, 131 participants) although the results could not be pooled due to very high heterogeneity (very low-quality of evidence). The third study reported that there was no evidence of a difference. We found there may be no evidence of a difference in the APGAR score (MD: 0.00, 95% CI -0.03 to 0.03, two studies,163 participants, low-quality evidence). Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, may not differ between groups (RR 1.19, 95% CI 0.87 to1.63, three studies, 166 participants, low-quality evidence). Only one study which compared methadone with buprenorphine reported side effects. We found there may be no evidence of a difference in the number of mothers with serious adverse events (AEs) (RR 1.69, 95% CI 0.75 to 3.83, 175 participants, low-quality evidence) and we found there may be no difference in the numbers of newborns with serious AEs (RR 4.77, 95% CI 0.59, 38.49,131 participants, low-quality evidence). Methadone versus slow-release morphine: There were no dropouts in either treatment group. Oral slow-release morphine may be superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants, low-quality evidence). In the comparison between methadone and slow-release morphine, no side effects were reported for the mother. In contrast, one child in the methadone group had central apnoea, and one child in the morphine group had obstructive apnoea (low-quality evidence).
AUTHORS' CONCLUSIONS
Methadone and buprenorphine may be similar in efficacy and safety for the treatment of opioid-dependent pregnant women and their babies. There is not enough evidence to make conclusions for the comparison between methadone and slow-release morphine. Overall, the body of evidence is too small to make firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.
Topics: Birth Weight; Buprenorphine; Delayed-Action Preparations; Female; Humans; Infant; Infant, Newborn; Methadone; Morphine; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic
PubMed: 33165953
DOI: 10.1002/14651858.CD006318.pub4 -
Substance Use & Misuse 2021Medications for opioid use disorder (MOUD) are evidence-based treatments, yet can be controversial among some populations. This study provides a systematic review of...
Medications for opioid use disorder (MOUD) are evidence-based treatments, yet can be controversial among some populations. This study provides a systematic review of prejudice and discrimination toward MOUD, a form of "intervention stigma," or stigma associated with a particular medical treatment. A systematic search strategy was used in PsychInfo and PubMed to identify studies published between 1998 and 2018. Studies that empirically examined stigma toward MOUD were included if the manuscript was of moderate or high quality. Studies were analyzed using thematic synthesis. The search yielded 972 studies, of which 28 were included. Most studies utilized qualitative methods to examine intervention stigma toward methadone or buprenorphine, with one including naltrexone. Studies demonstrated that intervention stigma among healthcare providers was influenced by lack of training and abstinent treatment preferences. Providers equated MOUD with illicit substance use and at times refused to care for MOUD patients. Stigma among peer patients seeking treatment was also influenced by abstinent treatment preferences, and among the general public stigma was influenced by lack of MOUD knowledge. Intervention stigma was also driven at the policy level by high regulation of methadone, which fueled diversion and hindered social functioning among patients. Few studies indicated how to reduce intervention stigma toward MOUD. Intervention stigma affects both provision and perceptions of methadone and buprenorphine, decreasing access and utilization of MOUD. Future research should further develop and test MOUD stigma reduction interventions in a variety of social contexts to improve access to care and reduce patient barriers.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 34538213
DOI: 10.1080/10826084.2021.1975749 -
Trends in Cardiovascular Medicine Apr 2023It is estimated that over 60 million individuals regularly use opioids globally, with opioid use disorder increasing substantially in the past decade. Several reports... (Review)
Review
BACKGROUND
It is estimated that over 60 million individuals regularly use opioids globally, with opioid use disorder increasing substantially in the past decade. Several reports have linked sudden cardiac death, QTc prolongation, and other adverse cardiovascular outcomes with opioid use through their inhibitory effect on the human ether-a-go-go-related gene (HERG) ion channel. Therefore, understanding this underlying mechanism may be critical for risk prevention and management in prescribing opioids and treating patients with opioid dependency.
AIM
The present systematic review summarizes the current literature on the impact of opioids-induced inhibition of HERG channel function and its relationship with sudden cardiac death, QTc prolongation, and other cardiovascular adverse effects.
METHODS
A systematic review was conducted of the databases PubMed, EMBASE, Cochrane, and ClinicalTrials.gov of primary studies that reported the effects of opioids on HERG channel function and associated cardiovascular outcomes.
RESULTS
The search identified 1,546 studies, of which 12 were finally included for data extraction. Based on the current literature, methadone, oliceridine, l-α-acetylmethadol (LAAM), and fentanyl were found to inhibit the HERG channel function and were associated with QTc prolongation. However, other opioids such as morphine, codeine, tramadol, and buprenorphine were not associated with inhibition of HERG channels or QTc prolongation. Additional cardiac outcomes associated with opioid related HERG channels dysfunction included sudden cardiac death and Torsade de Pointes.
CONCLUSION
Our findings suggest that certain opioid consumption may result in the inhibition of HERG channels, subsequently prolonging the QTc interval and increasing patient susceptibility to sudden cardiac death.
PubMed: 37015297
DOI: 10.1016/j.tcm.2023.03.006 -
Neuroscience and Biobehavioral Reviews May 2022Opioid use disorder is a significant global issue and the rate of opioid use in women of childbearing age and pregnant women is on the rise. Whilst the adverse general... (Meta-Analysis)
Meta-Analysis Review
Opioid use disorder is a significant global issue and the rate of opioid use in women of childbearing age and pregnant women is on the rise. Whilst the adverse general health, cognitive, and neurodevelopmental outcomes of in utero exposure to opioids have been explored, there is a lack of prospective, controlled, longitudinal research into the ophthalmic outcomes. Existing research suggests that there is an association between prenatal exposure and future risk of abnormalities in visual functioning. This systematic review and meta-analysis analysed studies that measured eye abnormalities in infants or children exposed to opioid maintenance therapy in utero and compared them to non-opioid exposed controls. After considering the clinical findings, limitations of the studies, confounding factors, and quantitative analysis, a causal relationship between in utero opioid exposure and future eye abnormalities could not be confirmed. The implications of the findings and their clinical relevance, in addition to identified gaps for future research are also discussed in this paper.
Topics: Analgesics, Opioid; Buprenorphine; Child; Female; Humans; Infant; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 35263646
DOI: 10.1016/j.neubiorev.2022.104601 -
Obstetrics and Gynecology Mar 2024Although naltrexone is an evidence-based medication for opioid use disorder (MOUD), few data are available with use in pregnancy. Our objective was to assess outcomes of...
OBJECTIVE
Although naltrexone is an evidence-based medication for opioid use disorder (MOUD), few data are available with use in pregnancy. Our objective was to assess outcomes of pregnant individuals with opioid use disorder (OUD) taking naltrexone compared with those taking methadone or buprenorphine.
DATA SOURCES
We undertook a systematic review using electronic database search (PubMed, CINAHL, EMBASE, PsycInfo), conference proceedings, and trial registries including ClinicalTrials.gov .
METHODS OF STUDY SELECTION
We conducted an electronic search of research articles through May 2023 for randomized controlled trials, prospective cohort, and retrospective cohort studies of naltrexone (oral, implant, or extended release) compared with methadone or buprenorphine (sublingual or extended release) among pregnant individuals with OUD. After double review of all articles, we abstracted obstetric (primary outcome: gestational age at delivery), neonatal (primary outcome: neonatal abstinence syndrome [NAS]), and substance use outcomes.
TABULATION, INTEGRATION, AND RESULTS
Five studies met eligibility criteria; four were retrospective cohort studies, and one was a prospective cohort study. Four studies included data on gestational age at delivery (weeks) with no difference detected between the two groups in any study (mean difference ranging -0.20, 95% CI, -1.49-1.09 to 0.8, 95% CI, -0.15 to 1.75). Three studies included data on NAS with all studies detecting a lower risk in the naltrexone group compared with methadone or buprenorphine (relative risk ranging from 0.08, 95% CI, 0.01-1.16 to 0.15, 95% CI, 0.06-0.36). Most studies (four of five) had a moderate or high potential for selection bias primarily driven by small sample size and lack of controlling for confounders.
CONCLUSION
Although the evidence base is limited, available data suggest that naltrexone use in pregnancy is a reasonable MOUD option with reassuring perinatal outcomes. To enhance confidence in this conclusion and to assess substance use outcomes, further comparative studies of pregnant people with OUD taking naltrexone and other MOUD types are needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, 42017074249.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Buprenorphine; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Retrospective Studies
PubMed: 38227945
DOI: 10.1097/AOG.0000000000005510 -
Frontiers in Psychiatry 2021Opioid dependence has been a threat to public health for hundreds of years. With the increasing number of studies on acupuncture-related therapies for opioid dependence...
Opioid dependence has been a threat to public health for hundreds of years. With the increasing number of studies on acupuncture-related therapies for opioid dependence patients receiving methadone maintenance treatment (MMT), its effect of acupuncture therapy in treating MMT patients remains controversial. Therefore, we conducted a multiple-treatments meta-analysis, and incorporated both direct and indirect comparisons, in order to discover the most effective treatment for opioid dependence patients receiving MMT. Five English databases and three Chinese databases were searched from its inception to August 20, 2020, in order to compare the effects of acupuncture-related therapies and MMT, which was summarized as Western medicine (WM) in the following texts. The quality of studies was assessed according to Cochrane's risk of bias tool 5.1.0, and a pair-wise meta-analysis, cumulative meta-analysis, and the network meta-analysis was performed using the R software (Version 3.6.1) and STATA (Version 14.0). The primary outcome was the effective rate, which was calculated by the ratio of detoxifying patients to the total. The secondary outcome was the Modified Himmelsbach Opiate Withdrawal Scale (MHOWS). A total of 20 trials were included, which consisted of comparisons among WM, traditional Chinese medicine (TCM), and the four types of acupuncture, namely, manual acupuncture (MA), electro-acupuncture (EA), auricular acupuncture (AA), and transcutaneous electrical acupoint stimulation (TEAS). Though none of the trials were at low risk of bias. In the pair-wise meta-analysis, no statistically significant differences were observed in terms of the effective rate. Furthermore, MA was more efficacious than WM, EA, and TEAS in MHOWS, with mean differences (MDs) of (-8.59, 95% CI: -15.96 to -1.23, < 0.01), (-6.15, 95% CI: -9.45 to -2.85, < 0.05), and (-10.44, 95% CI: -16.11 to -4.77, < 0.05), respectively. In the network meta-analysis, MA was more effective than WM (RR: 1.40, 95% CI: 1.05 to 1.99) on the effective rate, and (MD: -5.74, 95% CI: -11.60 to -0.10) on MHOWS. TEAS was more effective than WM (MD: -15.34, 95% CI: -27.34 to -3.46) on MHOWS. Synthetically, MA had the highest probability to rank first in treating opioid dependence. The existing evidence shows that acupuncture related-therapies may effectively be used for treating patients receiving MMT, and that manual acupuncture may be the best choice for opioid dependence among all kinds of acupuncture-related therapies. Nevertheless, reducing the relapse and promoting the recovery of opioid dependence need more efforts from not only the medical industry but also government support, security system, and educational popularization. To strengthen the assurance of acupuncture-related therapies in the treatment of opioid dependence, we expected that clinical trials with high quality would be conducted, to provide more confident evidence.
PubMed: 34966304
DOI: 10.3389/fpsyt.2021.767613 -
Addiction Science & Clinical Practice Oct 2021Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these... (Review)
Review
BACKGROUND
Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these substances may impact receipt of, and outcomes associated with, medications for OUD (MOUD). This systematic review identified studies that examined associations between methamphetamine/amphetamine use or use disorder and 3 classes of outcomes: (1) receipt of MOUD, (2) retention in MOUD, and (3) opioid abstinence during MOUD.
METHODS
We searched 3 databases (PubMed/MEDLINE, PsycINFO, CINAHL Complete) from 1/1/2000 to 7/28/2020 using key words and subject headings, and hand-searched reference lists of included articles. English-language studies of people with documented OUD/opioid use that reported a quantitative association between methamphetamine/amphetamine use or use disorder and an outcome of interest were included. Study data were extracted using a standardized template, and risk of bias was assessed for each study. Screening, inclusion, data extraction and bias assessment were conducted independently by 2 authors. Study characteristics and findings were summarized for each class of outcomes.
RESULTS
Thirty-nine studies met inclusion criteria. Studies generally found that methamphetamine/amphetamine use or use disorder was negatively associated with receiving methadone and buprenorphine; 2 studies suggested positive associations with receiving naltrexone. Studies generally found negative associations with retention; most studies finding no association had small samples, and these studies tended to examine shorter retention timeframes and describe provision of adjunctive services to address substance use. Studies generally found negative associations with opioid abstinence during treatment among patients receiving methadone or sustained-release naltrexone implants, though observed associations may have been confounded by other polysubstance use. Most studies examining opioid abstinence during other types of MOUD treatment had small samples.
CONCLUSIONS
Overall, existing research suggests people who use methamphetamine/amphetamines may have lower receipt of MOUD, retention in MOUD, and opioid abstinence during MOUD. Future research should examine how specific policies and treatment models impact MOUD outcomes for these patients, and seek to understand the perspectives of MOUD providers and people who use both opioids and methamphetamine/amphetamines. Efforts to improve MOUD care and overdose prevention strategies are needed for this population.
Topics: Buprenorphine; Humans; Methadone; Methamphetamine; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 34635170
DOI: 10.1186/s13722-021-00266-2 -
Journal of Substance Abuse Treatment Dec 2020The opioid epidemic is a public health crisis. Medications for opioid use disorder (MOUD) include: 1) buprenorphine, 2) methadone, and 3) extended-release naltrexone...
BACKGROUND
The opioid epidemic is a public health crisis. Medications for opioid use disorder (MOUD) include: 1) buprenorphine, 2) methadone, and 3) extended-release naltrexone (XR-NTX). Research should investigate patients' and providers' perspectives of MOUD since they can influence prescription, retention, and recovery.
METHODS
This systematic review focused on patients' and providers' perceptions of MOUD. The review eligibility criteria included inclusion of the outcome of interest, in English, and involving persons ≥18 years. A PubMed database search yielded 1692 results; we included 152 articles in the final review.
RESULTS
There were 63 articles about buprenorphine, 115 articles about methadone, and 16 about naltrexone. Misinformation and stigma associated with MOUD were common patient themes. Providers reported lack of training and resources as barriers to MOUD.
CONCLUSION
This review suggests that patients have significant misinformation regarding MOUD. Due to the severity of the opioid epidemic, research must consider the effects of patients' and providers' perspectives on treatment for OUD, including the effects on the type of MOUD prescribed, patient retention and adherence, and ultimately the number of patients treated for OUD, which will aid in curbing the opioid epidemic.
Topics: Buprenorphine; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 33138929
DOI: 10.1016/j.jsat.2020.108146 -
World Journal of Pediatrics : WJP May 2024Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome (SIDS) effects is lacking. We investigated the risk and... (Review)
Review
BACKGROUND
Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome (SIDS) effects is lacking. We investigated the risk and protective factors related to SIDS.
METHODS
We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related factors. PubMed/MEDLINE, Embase, EBSCO, and Google Scholar were searched from inception until January 18, 2023. Data extraction, quality assessment, and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA guidelines. According to observational evidence, credibility was graded and classified by class and quality of evidence (CE; convincing, highly suggestive, suggestive, weak, or not significant). Our study protocol was registered with PROSPERO (CRD42023458696). The risk and protective factors related to SIDS are presented as equivalent odds ratios (eORs).
RESULTS
We identified eight original meta-analyses, including 152 original articles, covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five continents. Several risk factors, including prenatal drug exposure [eOR = 7.84 (95% CI = 4.81-12.79), CE = highly suggestive], prenatal opioid exposure [9.55 (95% CI = 4.87-18.72), CE = suggestive], prenatal methadone exposure [9.52 (95% CI = 3.34-27.10), CE = weak], prenatal cocaine exposure [4.38 (95% CI = 1.95-9.86), CE = weak], prenatal maternal smoking [2.25 (95% CI = 1.95-2.60), CE = highly suggestive], postnatal maternal smoking [1.97 (95% CI = 1.75-2.22), CE = weak], bed sharing [2.89 (95% CI = 1.81-4.60), CE = weak], and infants found with heads covered by bedclothes after last sleep [11.01 (95% CI = 5.40-22.45), CE = suggestive], were identified. On the other hand, three protective factors, namely, breastfeeding [0.57 (95% CI = 0.39-0.83), CE = non-significant], supine sleeping position [0.48 (95% CI = 0.37-0.63), CE = suggestive], and pacifier use [0.44 (95% CI = 0.30-0.65), CE = weak], were also identified.
CONCLUSIONS
Based on the evidence, we propose several risk and protective factors for SIDS. This study suggests the need for further studies on SIDS-related factors supported by weak credibility, no association, or a lack of adequate research.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Meta-Analysis as Topic; Prenatal Exposure Delayed Effects; Protective Factors; Risk Factors; Sudden Infant Death
PubMed: 38684567
DOI: 10.1007/s12519-024-00806-1