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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 -
Anesthesia and Analgesia Dec 2019Methadone is a potent opioid exerting an analgesic effect through N-methyl-D-aspartate receptor antagonism and the inhibition of serotonin and noradrenaline reuptake. It... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Methadone is a potent opioid exerting an analgesic effect through N-methyl-D-aspartate receptor antagonism and the inhibition of serotonin and noradrenaline reuptake. It has also been used in several procedures to reduce postoperative pain and opioid use. This meta-analysis aimed to determine whether the intraoperative use of methadone lowers postoperative pain scores and opioid consumption in comparison to other opioids.
METHODS
Double-blinded, controlled trials without language restrictions were included from MEDLINE, Embase, LILACS, The Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL via EBSCOhost. The included studies tracked total opioid consumption, postoperative pain scores, opioid-related side effects, and patient satisfaction until 72 hours postoperatively. Mean difference (MD) was used for effect size.
RESULTS
In total, 476 articles were identified and 13 were considered eligible for inclusion in the meta-analysis. In 486 patients (7 trials), pain at rest (MD, 1.09; 95% confidence interval (CI), 1.47-0.72; P < .00001) and at movement (MD, 2.48; 95% CI, 3.04-1.92; P = .00001) favored methadone 24 hours after surgery. In 374 patients (6 trials), pain at rest (MD, 1.47; 95% CI, 3.04-1.02; P < .00001) and at movement (MD, 2.03; 95% CI, 3.04-1.02; P < .00001) favored methadone 48 hours after surgery. In 320 patients (4 trials), pain at rest (MD, 1.02; 95% CI, 1.65-0.39; P = .001) and at movement (MD, 1.34; 95% CI, 1.82-0.87; P < .00001) favored methadone 72 hours after surgery. A Trial Sequential Analysis was performed and the Z-cumulative curve for methadone crossed the monitoring boundary at all evaluations, additionally crossing Required Information Size at 24 and 48 hours at rest. Methadone group also showed lower postoperative opioid consumption in morphine equivalent dosage (mg) at 24 hours (MD, 8.42; 95% CI, 12.99-3.84 lower; P < .00001), 24-48 hours (MD, 14.33; 95% CI, 26.96-1.91 lower; P < .00001), 48-72 hours (MD, 3.59; 95% CI, 6.18-1.0 lower; P = .007) postoperatively.
CONCLUSIONS
Intraoperative use of methadone reduced postoperative pain scores compared to other opioids, and Trial Sequential Analysis suggested that no more trials are required to confirm pain reduction at rest until 48 hours after surgery. Methadone also reduced postoperative opioid consumption and led to better patient satisfaction scores through 72 hours postoperatively compared to other opioids.
Topics: Acute Pain; Analgesics, Opioid; Clinical Trials as Topic; Humans; Intraoperative Care; Methadone; Pain, Postoperative
PubMed: 31743194
DOI: 10.1213/ANE.0000000000004404 -
Innovations in Clinical Neuroscience 2017Opiate misuse is a chronic relapsing disease that has become an epidemic in the United States. Methadone is the mainstay of treatment for opiate addiction and has been... (Review)
Review
Opiate misuse is a chronic relapsing disease that has become an epidemic in the United States. Methadone is the mainstay of treatment for opiate addiction and has been researched widely. Recently, new avenues of treatment have been researched and developed. The objective of this review is to study methadone in comparison to other pharmacological options available or being considered for opiate addiction treatment through a methodical search and review of evidence provided by recent clinical trials conducted in this regard. There is a paucity of high quality randomized controlled trials focusing on the comparison between buprenorphine and methadone for treatment of opiate use disorder. Buprenorphine should be researched more for patient retention and satisfaction, as well as for its prospect for better outcomes in neonatal abstinence syndrome to generate more decisive recommendations. Current data suggest monitoring of liver enzymes with the use of buprenorphine/naloxone for better liver outcomes. In light of the analyzed data, the authors conclude that methadone should still be considered the preferred treatment mode in comparison to slow-release oral morphine and heroin.
PubMed: 29616150
DOI: No ID Found -
BMC Infectious Diseases Jun 2012Methadone maintenance treatment (MMT) was implemented in China since 2004. It was initiated in 8 pilot clinics and subsequently expanded to 738 clinics by the end of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methadone maintenance treatment (MMT) was implemented in China since 2004. It was initiated in 8 pilot clinics and subsequently expanded to 738 clinics by the end of 2011. Numerous individual research studies have been conducted to estimate HIV and HCV prevalence among MMT clients but an overview of the epidemics in relations to MMT remains unclear. The aim of this study is to estimate the magnitude and changing trends of HIV, HCV and HIV-HCV co-infections among entry clients to MMT clinics in China during 2004-2010.
METHODS
Chinese and English databases of literature were searched for studies reporting HIV, HCV and co-infection prevalence among MMT clients in China from 2004 to 2010. The prevalence estimates were summarized through a systematic review and meta-analysis of published literatures.
RESULTS
Ninety eligible articles were selected in this review (2 in English and 88 in Chinese). Nationally, pooled prevalence of HIV-HCV and HIV-HCV co-infection among MMT clients was 6.0% (95%CI: 4.7%-7.7%), 60.1% (95%CI: 52.8%-67.0%) and 4.6% (95%CI: 2.9%-7.2%), respectively. No significant temporal trend was found in pooled prevalence estimates. Study location is the major contributor of heterogeneities of both HIV and HCV prevalence among drug users in MMT.
CONCLUSIONS
There was no significant temporal trend in HIV and HCV prevalence among clients in MMT during 2004-2010. Prevalence of HCV is markedly higher than prevalence of HIV among MMT clients. It is recommended that health educational programs in China promote the earlier initiation and wider coverage of MMT among injecting drug users (IDUs), especially HIV-infected IDUs.
Topics: China; Coinfection; HIV Infections; Hepatitis C; Methadone; Opiate Substitution Treatment; Prevalence
PubMed: 22682091
DOI: 10.1186/1471-2334-12-130 -
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 -
A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence.Drug and Alcohol Review Mar 2014Naltrexone implants are used to treat opioid dependence, but their safety and efficacy remain poorly understood. We systematically reviewed the literature to assess the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION AND AIMS
Naltrexone implants are used to treat opioid dependence, but their safety and efficacy remain poorly understood. We systematically reviewed the literature to assess the safety and efficacy of naltrexone implants for treating opioid dependence.
DESIGN AND METHODS
Studies were eligible if they compared naltrexone implants with another intervention or placebo. Examined outcomes were induction to treatment, retention in treatment, opioid and non-opioid use, adverse events, non-fatal overdose and mortality. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Data from randomised studies were combined using meta-analysis. Data from non-randomised studies were presented narratively.
RESULTS
Five randomised trials (n = 576) and four non-randomised studies (n = 8358) were eligible for review. The quality of the evidence ranged from moderate to very low. Naltrexone implants were superior to placebo implants [risk ratio (RR): 0.57; 95% confidence interval (CI) 0.48, 0.68; k = 2] and oral naltrexone (RR: 0.57; 95% CI 0.47, 0.70; k = 2) in suppressing opioid use. No difference in opioid use was observed between naltrexone implants and methadone maintenance (standardised mean difference: -0.33; 95% CI -0.93, 0.26; k = 1); however, this finding was based on low-quality evidence from one study.
DISCUSSION
The evidence on safety and efficacy of naltrexone implants is limited in quantity and quality, and the evidence has little clinical utility in settings where effective treatments for opioid dependence are used.
CONCLUSION
Better designed research is needed to establish the safety and efficacy of naltrexone implants. Until such time, their use should be limited to clinical trials. [Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L. A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence.
Topics: Drug Implants; Humans; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Treatment Outcome
PubMed: 24299657
DOI: 10.1111/dar.12095 -
BMJ Clinical Evidence Jun 2007Dependence 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 June 2006 (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 21 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.
Topics: MEDLINE; Maintenance; United States; United States Food and Drug Administration
PubMed: 19454085
DOI: No ID Found -
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 -
The Cochrane Database of Systematic... Oct 2007Methadone is an opioid used in the management of cancer pain. A particular role in neuropathic pain has been suggested. The quest for evidence based palliative care... (Review)
Review
BACKGROUND
Methadone is an opioid used in the management of cancer pain. A particular role in neuropathic pain has been suggested. The quest for evidence based palliative care prompted a formal appraisal of methadone in comparison with other analgesics. This is an updated version of the original Cochrane review published in Issue 1, 2004.
OBJECTIVES
To determine effectiveness and safety of methadone analgesia in cancer pain patients.
SEARCH STRATEGY
MEDLINE, EMBASE, CancerLit, CINAHL and Cochrane databases were searched in 2002 using a strategy developed with the Cochrane Pain, Palliative and Supportive Care Group. Repeat searches were conducted in September 2006.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of methadone against active or placebo comparator in patients with cancer pain were included. Outcome measures sought were reduction in pain intensity, adverse effects, attrition, patient satisfaction and quality of life. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
Eligible studies were selected with independent collaboration from a colleague. Full text was retrieved if any uncertainty about eligibility remained. Non-English texts were screened by Cochrane contacts. Quality assessment and data extraction were conducted using standardised data forms. Drug and placebo dose, titration, route and formulation were compared and detail of all outcome measures (if available) recorded.
MAIN RESULTS
This updated review includes nine RCTs (six double blinded, two crossover) with 459 recruits and 392 completing patients. All studies involved active opioid comparators (morphine, dextromoramide, pethidine, diamorphine with cocaine mixture) with different dose and titration schedules and various pain scoring scales. One study differentiated cases by pain syndrome. Few presented complete pain data sets but complete adverse events data were recorded in every study. Efficacy and tolerability were broadly similar between methadone and morphine. No useful meta-analysis has been possible.
AUTHORS' CONCLUSIONS
The updated review contains new information supporting the previous conclusions that methadone has similar analgesic efficacy to morphine. The additional study examined neuropathic and non-neuropathic pain, finding no superiority for methadone in the former group. The new study also addresses a clinically relevant concern about short term/single dose studies. Use beyond a few days may result in methadone accumulation leading to delayed onset of adverse effects. In an assessment over 28 days there was a higher rate of withdrawal due to side effects in the methadone group. This observation reinforces the advice that experienced clinicians should take responsibility for initiation and careful dose adjustment and monitoring of methadone.
Topics: Analgesics, Opioid; Humans; Methadone; Morphine; Neoplasms; Pain; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 17943808
DOI: 10.1002/14651858.CD003971.pub3 -
Journal of Addiction MedicineTo review the currently available evidence on transfer strategies from methadone to sublingual buprenorphine used in clinical trials and observational studies of...
OBJECTIVES
To review the currently available evidence on transfer strategies from methadone to sublingual buprenorphine used in clinical trials and observational studies of medication for opioid use disorder treatment, and to consider whether any strategies yield better clinical outcomes than others.
METHODS
Six medical and public health databases were searched for articles and conference abstracts. The Cochrane Central Register of Controlled Trials and the World Health Organization International Clinical Trials Registry Platform were used to identify unpublished trial results. Records were dually screened, and data were extracted and checked independently. Results were summarized qualitatively and, when possible, analyzed quantitatively.
RESULTS
Eighteen studies described transfer from methadone to buprenorphine. Transfer protocols were extremely varied. Most studies reported successful rates of transfer, even among studies involving transfer from high methadone doses, although lower pretransfer methadone dose was significantly associated with higher rate of successful transfer. Precipitated withdrawal was not reported frequently. A range of innovative approaches to transfer from methadone to buprenorphine remains untested.
CONCLUSIONS
Few studies have used designs that enable comparison of different approaches to transfer patients from methadone to buprenorphine. Most international clinical guidelines provide recommendations consistent with the available evidence. However, clinical guidelines should be perceived as providing "guidance" rather than "protocols," and clinicians and patients need to exercise judgment when attempting transfers.
Topics: Buprenorphine; Humans; Methadone; Opioid-Related Disorders
PubMed: 33900228
DOI: 10.1097/ADM.0000000000000855