Methadone Group Research Articles

Compulsivity and impulsivity in opioid dependence

ObjectiveChronic exposure to illicit opioid drugs can cause serious health and social problems. However, less is known about the differential effect of various opioid treatments, such as methadone and buprenorphine, on neurocognitive domains such as compulsivity and impulsivity, despite their relevance to the treatment of opioid dependence. MethodsA total of 186 participants were recruited with a cross-sectional design: i) illicit heroin users (n = 27), ii) former heroin users stabilized on methadone MMT (n = 48), iii) a buprenorphine maintenance treatment (BMT) group (n = 18), iv) an abstinent (ABS) group with a history of opioid dependence who were previously stabilized on MMT or BMT (n = 29) and v) healthy controls (HC) (n = 64). We used the Intra-Extra Dimensional Shift (IED) and Cambridge Gambling Task (CGT) paradigms for measuring compulsivity and impulsivity constructs respectively. ResultsHeightened compulsivity persisted in the heroin, buprenorphine and abstinent groups. Heroin, methadone and buprenorphine groups exhibited impaired behavioral responses to feedback, consisting of increased deliberation time and poorer risk adjustment. Higher compulsivity measures were negatively associated with opioid dose which may reflect sedation effects. ConclusionsOur results suggest that compulsivity and impulsivity are core neurocognitive dimensions for opioid dependence which differ in their presentation according to the stage of treatment. Participants taking higher morphine equivalent doses performed better in compulsivity measures. These findings have implications for the treatment of opioid dependence and longitudinal studies are warranted.

Intraoperative Intravenous Methadone and Ketamine Combination versus Intravenous Morphine and Ketamine Combination for Post-Operative Analgesia in Patients Undergoing Lower Extremity Fracture Surgery

Background: Pain management for lower extremity fracture surgeries can be challenging. The purpose of this study is to determine whether the use of ketamine and methadone are more effective than ketamine and morphine to reduce postoperative pain and morphine requirements in patients undergoing lower extremity fracture surgery. Materials and Methods: Seventy-five patients 18-65 years of age, ASA class I-III, were enrolled in this study, which scheduled for elective lower extremity orthopedic surgery involving fracture of femur or tibia were recruited for the study. Thirty-eight randomized to the Methadone group and 37 randomized into the Morphine group. Participants were randomized to either one of the two groups: methadone (2ug/kg fentanyl, 0.2 mg/kg ketamine and 0.2 mg/kg methadone IV) versus control (2 ug/kg fentanyl, 0.2mg/kg ketamine and 0.2 mg/kg morphine IV). The primary outcome was total morphine equivalent (MEQ) during the first 24 and 48 hours after surgery. Secondary outcomes included postoperative pain scores in PACU, at 24 and 48 hours, as well as postoperative nausea and vomiting (PONV). Results: There was no difference in intraoperative consumption of fentanyl between the Methadone group 360mcg and Morphine group 344mcg. In the first 24 hours postoperatively, the Methadone group consumed less MEQ compared with the Morphine group (36.1 mg vs 54.8 mg, p=0.0072), showed lower pain scores than the Morphine group (p=0.0146), and experienced more nausea and vomiting than the Morphine group. There were no differences in sedation in both groups. Conclusion: The intraoperative use of intravenous methadone significantly reduced post-operative opioid requirement in patients undergoing lower extremity fracture surgery. The results also demonstrated the methadone group had a higher rate of PONV.

Evaluation of functional status among patients undergoing maintenance treatments for opioid use disorders

BackgroundMethadone and buprenorphine are the most prevalent types of opioid maintenance programs in Andalusia. The main objective is comparing the functional status of patients with pharmacological opioid maintenance treatments according to different socio-demographic characteristic, health and disabilities domains and sexual difficulties.MethodsA total of 593 patients from the Andalusia community, 329 were undergoing methadone treatment and 264 were undergoing buprenorphine treatment. The patients were interviewed by socio-demographic and opioid-related variables, assessed by functioning, disability and health domains (WHODAS 2.0.) and for sexual problems (PRSexDQ-SALSEX).ResultsWe found significant differences in the socio-demographic and the opioid-related variables as the onset of opioid use, being on previous maintenance programs, opioid intravenous use, the length of previous maintenance programs, polydrug use and elevated seroprevalence rates (HCV and HIV) between the methadone group and the buprenorphine group. Regarding health and disability domains there were differences in the Understanding and communication domain, Getting around domain, Participation in society domain and in the WHODAS 2.0. simple and complex score, favoring buprenorphine-treated patients. The methadone group referred elevated sexual impairments compared with the buprenorphine group. Opioid-related variables as seroprevalence rates, other previous lifetime maintenance program, the daily opioid dosage and the daily alcohol use are the most discriminative variables between both groups. Participation in society variables and sexual problems were the most important clinical variables in distinguishing the methadone group from the buprenorphine group regarding their functional status.ConclusionsThe methadone group showed higher prevalence in opioid dependence-related variables, elevated disabilities in participation in society activities and sexual problems compared with the buprenorphine group. This study shows the importance of carry out a functional evaluation in the healthcare follow-up, especially in those areas related with social activity and with sexual problems.

Effect of intraoperative methadone vs other opioids on postoperative outcomes: a meta-analysis of randomized controlled studies.

Recent randomized controlled trials comparing the efficacy between intraoperative methadone and other opioids on postoperative outcomes have been limited by their small sample sizes and conflicting results. We performed a meta-analysis on randomized controlled trials which investigated outcomes between methadone and an opioid control group. Primary outcome data included postoperative opioid consumption, number of patients who received postoperative opioids, time to first analgesic, and pain scores. Secondary outcomes included time to extubation and incidence of nausea, vomiting, and respiratory depression. Statistical analysis was performed using RevMan. A P < 0.05 was considered statistically significant. Nine studies comprising 632 patients were included. There was no statistically significant reduction in opioid consumption postoperatively between the groups. Forty-seven percentage of patients in the methadone group received a dose of opioid postoperatively compared with 55% in the other opioids control group, which was not statistically significant. (P = 0.25) There was no difference in average time to receiving first postoperative analgesic among the groups. Pain scores within 24 hours were significantly lower in the methadone group when compared with other opioids (8 studies, n = 622, -0.49 [-0.74, -0.23], P = 0.002). However, there was no difference between 24 and 72 hours. There was no difference among the groups with respect to extubation time, nausea, vomiting, or respiratory depression. This meta-analysis concludes that there is currently insufficient evidence for the use of intraoperative methadone, when compared with other opioids. Although there was a decrease in average pain scores with methadone when compared with controls at 24 hours, there was no difference between 24 and 72 hours.

587 Methadone and Morphine for Outpatient CO2 Laser Pain Management

Abstract Introduction Burn reconstruction with CO2 laser is now very popular. Providing adequate analgesia is imperative for large total body surface area (TBSA) resurfacing. CO2 lasers’ cause significant pain during the procedure and pain similar to that of a severe sunburn post-operatively. Thus, adequate analgesia that provides peri-operative and post discharge management without delaying discharge is beneficial. At our institution, we use a multimodal analgesic preoperative and intra-operative approach to deal with this issue. The preoperative intervention utilizes a novel approach of oral methadone for older children and avoids the use of intra-operative morphine as a preemptive measure for pain management. The purpose of this outcomes review was to determine if our peri-operative analgesic practices were effective in controlling peri-operative pain. Methods After corporate IRB review, this project was undertaken as a quality improvement initiative and was not formally supervised by an institutional review board. A chart review of all patients who received CO2 laser treatment (CLT) was conducted. Using a Donabedian model for outcomes measure, postoperative and pre-discharge observational pain scores (scale 1–10), peri-operative analgesics, demographics, percent burn treated, incidents of rescue medication before discharge home, time to discharge and adverse reactions were collected. Results 74 patients were reviewed (47 male, 27 female), ages 4 to 30, average age 17. Average percent body surface area treated was 17.5%. Out of 74 cases, 18 received intra-operative morphine and 56 received oral methadone pre-operatively. All patients received routine intra-operative ketorolac and lidocaine/prilocaine cream, based on weight. In the PACU there were 2 recorded rescue doses of morphine in the morphine group and 0 in the methadone group. There was one post- operative recorded observational pain score of 5 in the methadone group and one each of 3 and 8 in the morphine group, both of which received rescue morphine. There were no differences in mean times to discharge between groups. Observational pain scores were 0 for both groups at discharge. Chi square analysis showed no statistical difference between groups. No adverse outcomes (respiratory arrest or readmission for pain) were recorded in either group. Conclusions Both pre-operative oral methadone and intra-operative morphine are effective in controlling peri-operative pain in our children undergoing laser surgery. Categorical age differences and low group sizes may have contributed to outcomes and should be considered in the next review.

Discovering Non-Invasive Biomarkers Predictive of Opioid Use Disorder Treatment Response

Opioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone. We obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing. We found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls. Naltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.

589 Methadone in Procedural Care for Burn Injuries of 20–30% Total Burn Surface Area: A Retrospective Chart Review

Abstract Introduction Prolonged opioid usage remains a concern in pain management in procedural care. Recent evidence also suggests that a considerable number of patients who were prescribed opioids struggle with transitioning to non-opioid pain medications. As a continuous effort to reduce opioid consumption following burn surgical procedures, our institution recently evaluated methadone administration for burn procedural care in patients with 20–30% total burn surface area (TBSA) requiring excision and grafting. Methods After IRB approval, we performed a retrospective chart review of patients who underwent excision and grafting procedure for 20–30% TBSA burn injuries between January 1, 2019 and June 30, 2020. The following data was evaluated: postoperative opioid consumption, postoperative pain intensity (rated as “No Pain” [NRS=0], “Minor Pain” [NRS 1 to 3], “Moderate Pain” [NRS 4 to 6], “Severe Pain” [NRS 7 to 10]), time to physical therapy and time to hospital discharge. Data was analyzed using chi square/Fisher exact test for categorical variables and t-test/Wilcoxon rank sum test for continuous variables. Results Our preliminary data included 12 patients who met inclusion criteria, of which two patients received methadone administration. Our patient sample consisted of average age of 43 years, 75% male, and 24% TBSA (92% were flame burns). Patients in both methadone and non-methadone groups had no significant differences in medical histories and TBSA (23% TBSA in methadone, 25% TBSA in non-methadone). There was no significant difference in reported preoperative pain intensity between the two groups, rating moderate to severe. Postoperative pain intensity remained the same, rating moderate to severe and controlled with fentanyl, oxycodone, morphine and non-opioid analgesics. While there was no difference in postoperative fentanyl, opioid and non-opioid analgesic consumptions between the two groups, morphine consumption was significantly lower in the methadone group compared to non-methadone group (2±2 mg vs 51±54 mg, respectively, p=0.02). There was no significant difference between average time from surgery to first physical therapy session and time to hospital discharge (about 21 days after surgery) between the two groups. Conclusions This evaluation shows a potential trend in reduction of inpatient postoperative opioid consumption with the conjunctive administration of methadone, although a bigger sample size is needed for further assessment.

Efficacy of methadone for the management of postoperative pain in laparoscopic cholecystectomy: A randomized clinical trial.

Postoperative pain management contributes to reducing postoperative morbidity and unscheduled readmission. Compared to other opioids that manage postoperative pain like morphine, few randomized trials have tested the efficacy of intraoperatively administered methadone to provide evidence for its regular use or be included in clinical guidelines. We conducted a randomized clinical trial comparing the use of intraoperative methadone to assess its impact on postoperative pain. Eighty-six patients undergoing elective laparoscopic cholecystectomy were allocated to receive either methadone (0.08 mg/kg) or morphine (0.08 mg/kg). Individuals who received methadone required less rescue morphine in the Post Anesthesia Care Unit for postoperative pain than those who received morphine (p = 0.0078). The patients from the methadone group reported less pain at 5 and 15 minutes and 12 and 24 hours following Post Anesthesia Care Unit discharge, exhibiting fewer episodes of nausea. Time to eye-opening was equivalent between the two groups. Intraoperative use of methadone resulted in better management of postoperative pain, supporting its use as part of a multimodal pain management strategy for laparoscopic cholecystectomy under remifentanil-based anesthesia.

Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial.

Despite application of multimodal pain management strategies, patients undergoing spinal fusion surgery frequently report severe postoperative pain. Methadone and ketamine, which are N-methyl-d-aspartate receptor antagonists, have been documented to facilitate postoperative pain control. This study therefore tested the primary hypothesis that patients recovering from spinal fusion surgery who are given ketamine and methadone use less hydromorphone on the first postoperative day than those give methadone alone. In this randomized, double-blind, placebo-controlled trial, 130 spinal surgery patients were randomized to receive either methadone at 0.2 mg/kg (ideal body weight) intraoperatively and a 5% dextrose in water infusion for 48 h postoperatively (methadone group) or 0.2 mg/kg methadone intraoperatively and a ketamine infusion (0.3 mg · kg-1 · h-1 infusion [no bolus] intraoperatively and then 0.1 mg · kg-1 · h-1 for next 48 h [both medications dosed at ideal body weight]; methadone/ketamine group). Anesthetic care was standardized in all patients. Intravenous hydromorphone use on postoperative day 1 was the primary outcome. Pain scores, intravenous and oral opioid requirements, and patient satisfaction with pain management were assessed for the first 3 postoperative days. Median (interquartile range) intravenous hydromorphone requirements were lower in the methadone/ketamine group on postoperative day 1 (2.0 [1.0 to 3.0] vs. 4.6 [3.2 to 6.6] mg in the methadone group, median difference [95% CI] 2.5 [1.8 to 3.3] mg; P < 0.0001) and postoperative day 2. In addition, fewer oral opioid tablets were needed in the methadone/ketamine group on postoperative day 1 (2 [0 to 3] vs. 4 [0 to 8] in the methadone group; P = 0.001) and postoperative day 3. Pain scores at rest, with coughing, and with movement were lower in the methadone/ketamine group at 23 of the 24 assessment times. Patient-reported satisfaction scores were high in both study groups. Postoperative analgesia was enhanced by the combination of methadone and ketamine, which act on both N-methyl-d-aspartate and μ-opioid receptors. The combination could be considered in patients having spine surgery.

Impact of Intravenous Methadone Administered Intraoperatively on Postoperative Opioid Utilization.

Studies have shown that intravenous methadone intraoperatively can reduce opioid usage postoperatively. This study's purpose was to evaluate the effect of intravenous methadone on postoperative opioid use. A prospective, single-center observational study was conducted to evaluate patients who received intravenous methadone intraoperatively. A control group was identified by matching procedure, gender, and age in a 1:3 ratio of methadone to control. Exclusion criteria included patients less than 18 years old or on methadone maintenance therapy. The primary outcome was morphine milligram equivalents (MME) administered 24h postoperatively. Secondary outcomes included MME administered 48h and 72h postoperatively, discharge prescription MME, daily mean postoperative pain scores, and length of hospital stay. A subgroup analysis was performed comparing opioid-naïve patients. A total of 240 patients were included in the analysis. At 24h, postoperative MME was increased in the methadone group (142.6 vs 84.5; P = 0.0026). Postoperative MME was also increased in the methadone group at 48h and 72h. Daily pain scores were similar between both groups at all time intervals. Discharge prescription MME was reduced in the methadone group compared with controls, but not statistically significant. A subgroup analysis of opioid-naïve patients showed a significant reduction in MME at 48h (P = 0.0240) and daily pain scores at 24h (P = 0.0366) in the methadone group. Intravenous methadone intraoperatively did not show a significant reduction in postoperative opioid use and discharge prescription MMEs when comparing all patients; however, benefit was seen when examining opioid-naïve patients.

Unintentional buprenorphine and methadone poisoning in children: a matched observational study

Objective To compare accidental pediatric poisoning from methadone vs. buprenorphine in terms of clinical indicators and in-hospital morbidity. Methods A matched observational study conducted on children aged ≤12 years admitted to our center between March 2018 and March 2019 with acute poisoning from methadone or buprenorphine. Data were extracted from the electronic patient files of the pediatric methadone poisoning cases, and buprenorphine poisoning cases were followed from ED, during the study period. Cases were compared regarding rates of bradypnea/apnea (primary outcome), the need for antidote therapy and intubation, duration of hospital stay, miosis, loss of consciousness, blood gas analyses, and mortality (secondary outcomes). Results A total of 90 methadone- and 30 buprenorphine-poisoned children were evaluated. Methadone cases had significantly higher rates of apnea (20/90 methadone vs. 0/30 buprenorphine; OR = 17.7, 95% CI 1.1, 302.8; p = 0.047), but there was no group difference in bradypnea (39/90 methadone vs. 10/30 buprenorphine; p = ns). 28 (31%) methadone and 3 buprenorphine (10%) cases had been referred to as fully awake (p = 0.013). Methadone cases required higher median naloxone doses for initial bolus (0.4 vs. 0.02 mg; p = 0.014) and maintenance infusion (14.4 vs. 2.4 mg; p < 0.001). 20 apnea cases (all from the methadone group) had miotic pupils, and miotic pupils were seen in 44 (90%) cases with bradypnea (OR = 3.2, 95% CI 1.1, 9.3; p = 0.026). Intubation was needed in only 5 methadone cases (5.5%; p = ns). All patients survived. Conclusion Compared to children poisoned with methadone, buprenorphine cases had higher rates of loss of consciousness on admission but subsequently experienced fewer complications during hospital treatment, which is likely due to the buprenorphine partial antagonist effect. Our findings suggest that methadone exposure is more toxic than buprenorphine in pediatric populations.

Common Opioids Involved in Drug Poisoning Presenting to the Emergency Department: A Cross-sectional Study.

Objective:Opioids poisoning is of the most important cause of mortality. The objective of the study was to compare the demographic factors, clinical manifestations, and outcomes of the most common opioids involved in drug overdose presenting to the Emergency Department.Methods:This cross-sectional study was conducted from October 2016 to March 2017 in the Clinical Toxicology Department of the main referral center of the university. All poisoning cases with common opioids were included in the study. Demographic factors, clinical manifestations, and outcome were recorded in a check list. ANOVA, Chi-square or Fisher's exact test, and binary logistic regression analysis were used for outcome prediction.Findings:Two hundred and thirty six patients with opioids poisoning were evaluated during the study period. The most common opioids involved in poisoning were methadone (47.9%), tramadol (24.2%), and opium (21.6%). Patients with opium poisoning were older than others (P < 0.0001). The rate of suicide was more in the tramadol group, while the past history of psychological problems was more observed in the methadone group (P < 0.0001). Increasing age (odds ratio [OR], 1.05; 95% confidence interval [CI]: 1.02–1.09; P = 0.05) and addiction (P = 0.01; OR, 7; 95% CI: 1.55–31.52) was associated with an increased complications or death. Also patients with somatic disease had more chance of complications/death (P = 0.04; OR, 3.71; 95% CI: 1.06–12.97). Kind of opioids was not a predictive factor in the outcome of the patients with acute poisoning.Conclusion:Age, addiction, and somatic disease should be considered as more important factors in outcome prediction with opioids poisoning, including opium, tramadol, and methadone.

Post-Cesarean Delivery Analgesic Outcomes in Patients Maintained on Methadone and Buprenorphine: A Retrospective Investigation.

BackgroundDespite the increasing prevalence of opioid use disorder (OUD) in pregnant women, there are limited studies on their anesthesia care and analgesic outcomes after cesarean delivery (CD).MethodsPatients with OUD on either buprenorphine or methadone maintenance therapy who underwent CD at our institution from 2011 to 2018 were identified. Anesthetic details and analgesic outcomes, including daily opioid consumption and pain scores, were compared between patients maintained on buprenorphine and methadone. Analgesic outcomes were also evaluated according to anesthetic type (neuraxial or general anesthesia) and daily buprenorphine/methadone dose to determine if these factors impacted pain after delivery.ResultsA total of 146 patients were included (buprenorphine n=99 (67.8%), methadone n=47 (32.2%)). Among all patients: 74% had spinal/CSE, 15% epidural, and 11% general anesthesia. Anesthesia types were similar among buprenorphine and methadone patients. For spinal anesthetics, intrathecal fentanyl (median 15 µg) and morphine (median 100 µg) were commonly given (97.2% and 96.3%, respectively), and dosed similarly between groups. Among epidural anesthetics, epidural morphine (median 2 mg) was commonly administered (90.9%), while fentanyl (median 100 µg) was less common (54.5%). Buprenorphine and methadone groups consumed similar amounts of oxycodone equivalents per 24 hours of hospitalization (80.6 vs 76.3 mg; p=0.694) and had similar peak pain scores (8.3 vs 8.0; p=0.518). Daily methadone dose correlated weakly with opioid consumption (R=0.3; p=0.03), although buprenorphine dose did not correlate with opioid consumption or pain scores. General anesthesia correlated with greater oxycodone consumption in the first 24 hours (median 156.1 vs 91.7 mg; p=0.004) and greater IV PCA use (63% vs 7%; p<0.001) compared to neuraxial anesthesia.ConclusionPatients on buprenorphine and methadone had similar high opioid consumption and pain scores after CD. The anesthetic details and analgesic outcomes reported in this investigation may serve as a useful reference for future prospective investigations and aid in the clinical care of these patients.

Maintenance agonist treatments for opiate-dependent pregnant women.

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. 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. 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). Randomised controlled trials which assessed the efficacy of any pharmacological maintenance treatment for opiate-dependent pregnant women. We used the standard methodological procedures expected by Cochrane. 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). 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.

Comparison of buprenorphine and methadone in the management of maternal opioid use disorder in full term pregnancies.

Objectives To compare pregnancy outcomes with medication assisted treatment using. methadone or buprenorphine in term mothers with opioid use disorder. Methods A cohort of women receiving medication assisted treatment with either methadone or buprenorphine were identified from delivery records over a 10-year period. Women were excluded with delivery<37weeks, multiple gestations, or a known anomalous fetus. Maternal demographics, medications, mode of delivery, birthweight, newborn length of stay, and neonatal abstinence syndrome were extracted. The study was IRB approved and a p-value of<0.05 was significant. Results There were 260 women, 140 (53.8%) with methadone use and 120 (46.2%) with buprenorphine use. Groups were similar for maternal age, race, parity, homeless rate, tobacco use, mode of delivery and incidence of neonatal abstinence syndrome. The methadone group had a lower mean newborn birthweight (2874±459g) and a greater incidence of low birth weight (11.4%) than the buprenorphine group (3282±452g; p<0.001 and 2.5%; p=0.006). The incidence of neonatal abstinence syndrome was similar between groups (97% methadone vs. 92.5% buprenorphine; p=0.08). The methadone group had a longer newborn length of stay (11.4+7.4days) and more newborn treatment with morphine (44.6%) than the buprenorphine group (8.2+4.4days; p<0.001 and 24.2%; p<0.001). Maternal methadone use was an independent predictor for a newborn length of hospital stay>7days (OR 3.61; 95% confidence interval 1.32-9.86; p=0.01). Conclusions Medication assisted treatment favors buprenorphine use when compared to. methadone with an increased birthweight, reduced need for newborn treatment, and a shorter newborn length of stay in term infants.

Adverse neonatal outcomes associated with maternal severe mental health diagnoses and opioid use.

Determine odds ratios for neonatal abstinence syndrome (NAS) and neonatal intensive care unit (NICU) admissions for babies born to women associated with severe mental illness (SMI) and gestational opioid use. A retrospective pharmacoepidemiologic study using Medicaid data included 17,130 mothers with and 170,430 mothers without SMI, and their babies. Odds ratios for NAS and NICU admissions among babies born to mothers associated with SMI diagnoses and associated with varying degrees of gestational opioid use were determined using logistic regression. The adjusted odds ratio for a baby in the methadone or buprenorphine group having NAS was 168.93 [95% confidence interval (CI) 148.78-191.71, P < 0.001] and was 9.64 (95% CI 8.74-10.65, P < 0.001) for NICU admissions compared to babies with no opioid exposure. Chronicity of prescription maternal opioid use was the strongest factor associated with NAS and NICU admissions.

Time-Dependent Changes in the Serum Levels of Neurobiochemical Factors After Acute Methadone Overdose in Adolescent Male Rat.

Acute methadone toxicity is a major public health concern which has adverse effects on brain tissue and results in recurrent or delayed respiratory arrest. Our study aimed to investigate the time-dependent changes in several serum biochemical markers of brain damage, spatial working memory, and the brain tissue following acute methadone overdose. Adolescent male rats underwent an intraperitoneal (i.p.) injection of 15mg/kg methadone. In case of apnea occurrence, resuscitation was performed by a ventilatory pump and administrating naloxone (2mg/kg; i.p.). The animals were classified into groups of treated rats; methadone and naloxone-Apnea (M/N-Apnea), M/N-Sedate, Methadone, Naloxone, and control (saline) groups. The serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein factors, and (Lactate/Pyruvate) L/P ratio were evaluated at the time-points of 6, 24, and 48h (h). We found that the alterations of S100B and L/P ratio were considerable in the M/N-Apnea and Methadone groups from the early hours post-methadone overdose, while NSE serum levels elevation was observed only in M/N-Apnea group with a delay at 48h. Further, we assessed the spatial working memory (Y-maze test), morphological changes, and neuronal loss. The impaired spontaneous alternation behavior was detected in the M/N-Apnea groups on days 5 and 10 post-methadone overdose. The morphological changes of neurons and the neuronal loss were detectable in the CA1, striatum, and cerebellum regions, which were pronounced in both M/N-Apnea and Methadone groups. Together, our findings suggest that alterations in the serum levels of S100B and NSE factors as well as L/P ratio could be induced by methadone overdose with the presence or absence of apnea before the memory impairment and tissue injury in adolescent male rats.

Associations of Maternal Prenatal Drug Abuse With Measures of Newborn Brain Structure, Tissue Organization, and Metabolite Concentrations

Increasing rates of illicit drug use during pregnancy may be associated with risk for long-term health problems in prenatally exposed children. To identify the associations of prenatal exposure to illicit drugs with organization of the newborn brain. For this cohort study, a volunteer sample of 210 illicit drug-using and nonusing mothers and their newborns was enrolled from prenatal clinics and drug abuse treatment programs in New York, New York. Enrollment, scanning, and long-term follow-up occurred from September 2004 through February 2012, and image processing and statistical analyses continued through fall 2018. In addition to 26 participants with incomplete data, a total of 64 mothers were lost to follow-up during pregnancy, and 13 newborns were lost to follow-up at birth because of perinatal complications. Newborns were assigned to 1 of 4 primary exposure groups based on the history of most frequent maternal drug use: marijuana, cocaine, methadone maintenance, and/or heroin. Unexposed newborns were controls. Unsedated magnetic resonance imaging (MRI) of newborn brains was performed shortly after birth. Infant neurodevelopmental outcomes were assessed at age 12 months. MRI modalities included anatomical imaging, diffusion tensor imaging, T2 relaxometry, and magnetic resonance spectroscopic imaging. Infant neurodevelopmental outcomes included Bayley scales of infant development-III and Vineland Adaptive Behavior Scales. Statistical analyses were performed with results represented on the brain images. Of 118 mothers, 42 (35%) were in the control group (mean [SD] age, 25.9 [6.1] years), 29 (25%) were in the cocaine group (mean [SD] age, 29.0 [6.1] years), 29 (25%) were in the marijuana group (mean [SD] age, 24.3 [5.5] years), and 18 (15%) were in the methadone and/or heroin group (mean [SD] age, 30.9 [5.7] years). Not all newborns could be scanned successfully; therefore, usable MRIs were acquired for 118 newborns from predominantly minority groups and with economically disadvantaged mothers. Anatomic abnormalities were detected in similar locations across all 3 drug exposures and included smaller volumes in the dorsal, medial, and ventral surfaces of the frontal lobe and dose-related increases in volumes in the lateral temporal lobe, dorsal parietal lobe, and superior frontal gyrus. Dose-related increases in diffusion tensor measures of tissue organization, decreases in T2 relaxometry times, and increases in spectroscopy metabolite concentrations were similar across exposures. These associations of exposures with brain measures were similar to the associations of newborn age with brain measures. The anatomic and diffusion tensor imaging measures suppressively mediated the associations of prenatal exposure with poorer 12-month infant outcomes. The findings suggest that prenatal drug exposure is associated with measures of newborn brain tissue in patterns that may indicate that exposures accelerated normal fetal brain maturation, which in turn mediated the associations with poorer 12-month infant outcomes.

Comparing the Efficacy of Methadone and Tincture of Opium in Controlling Agitation Caused by Withdrawal Syndrome in Opium-Addicted Patients in the Intensive Care Unit: A Randomized Trial Study.

BackgroundFew studies have been conducted regarding the comparison of the efficacy of methadone and tincture of opium (TOP) in controlling agitation induced by withdrawal syndrome. Therefore, the current randomized trial study is carried out with the aim to evaluate comparisons on the efficacy of methadone and TOP in controlling agitation caused by withdrawal syndrome in opium addicted patients in the intensive care units (ICUs).MethodsThis clinical trial study was conducted on 60 patients admitted to ICU of Shahid Bahonar Hospital, Kerman, Iran. After classification of the patients into two groups, the first and second groups consumed methadone syrup (5 mg/ml) and TOP (10 mg/ml), respectively. Agitation in these patients was assessed through the Richmond Agitation-Sedation Scale (RASS). Vital signs were also assessed. Paired sample t-test and independent t-test were used for data analysis.FindingsIn the current study, the administered dose of methadone and TOP was 36.17 ± 26.99 and 112.67 ± 102.74 mg, respectively (P < 0.010). Methadone administration led to a significant decrease of the patients’ vital signs, including systolic blood pressure, heart rate, respiratory rate, and Glasgow Coma Scale (GCS) (P < 0.05). Though TOP administration decreased systolic blood pressure and GCS significantly (P < 0.05), it had no effect on patients’ diastolic blood pressure, body temperature, heart rate, and respiratory rate (P > 0.05). In total, no significant difference was detected between two groups regarding vital signs (P > 0.05). However, a significant difference was seen between methadone and TOP groups in terms of RASS score (P < 0.01).ConclusionAccording to the results of the current study, lower dose of methadone, compared to TOP, could control agitation caused by opium withdrawal symptoms.

GAD1 but not GAD2 polymorphisms are associated with heroin addiction phenotypes

IntroductionHeroin addiction is a chronic complex brain disease that contains multiple phenotypes, which vary widely among addicts and may be affected by genetic factors. A total of 801 unrelated heroin addicts were recruited and divided into different subgroups according to eight phenotypes of heroin addiction. Polymorphisms in GAD1 (rs3762555, rs3762556, rs3791878, rs3749034, rs11532313 and rs769395) and GAD2 (rs2839669, rs2839670 and rs2236418) were genotyped using the SNaPshot assay. Associations between genetic variants and the eight phenotypes were mainly assessed by binary logistic regression. ResultsWe found that the frequencies of G allele of GAD1 rs3749034 and rs3762555 were associated with daily dose of methadone use and memory change after heroin addiction. The C allele frequency of GAD1 rs3762556 was associated with lower daily dose of methadone use. In GAD1, SNPs rs3762556, rs3762555, rs3791878 and rs3749034 had strong linkage, and the frequency of the C-G-C-A haplotype was higher in the lower dose of methadone group. Patients with the TT genotype of rs11542313 were maintained on lower dose of methadone than patients with the CC genotype. The G alleles of rs3762555 and rs3749034 were lower, while the T allele of rs11542313 was higher, in the memory decreased group. The results of association analyses of GAD2 with phenotypes of heroin addiction showed no significant differences. ConclusionGAD1 polymorphisms were associated with phenotypes of heroin addiction, especially the daily dose of methadone use and memory change in the Han Chinese population. These results may provide individualized guidance for the treatment of heroin addiction.