Maternal Opioid Treatment: Human Experimental Research Research Articles

Pregnancy intention and opioid use disorder treatment retention in the MOTHER study.

Opioid use disorder (OUD) during pregnancy challenges public health. This study examines how pregnancy intention affects OUD treatment. The primary exposure and outcome were pregnancy intention and treatment duration among MOTHER (Maternal Opioid Treatment: Human Experimental Research) participants (N = 175). Treatment durations were longer (21.3 vs. 16.3 weeks; p = .01) among intended (n = 29) compared to unintended (n = 146) pregnancy participants, but this was not significant in adjusted analyses. Unintended pregnancies intersect with OUD and may modify one's treatment outcomes. OUD treatment may be a setting to help women implement informed family planning choices. (Am J Addict 2018;XX:1-3).

Psychometric assessment of the Neonatal Abstinence Scoring System and the MOTHER NAS Scale.

The present study examined the psychometric characteristics of the Neonatal Abstinence Scoring System (NASS; "Finnegan Scale") and the MOTHER NAS Scale (MNS). Secondary analysis of data from 131 neonates from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a randomized trial in opioid-dependent pregnant women administered buprenorphine or methadone. Both the NASS and MNS demonstrated poor psychometric properties, with internal consistency (Cronbach's αs) failing to exceed .62 at first administration, peak NAS score, and NAS treatment initiation. Findings support the need for development of a NAS measure based on sound psychometric principles. This study found that two frequently used measures of neonatal abstinence syndrome suffer inadequacies in regard to their basic measurement characteristics. (Am J Addict 2016;25:370-373).

Scientific evaluation on substance abuse research through web of science over the 2008–2012 period

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e149 agonist treatment for opioid dependence utilized postpartum reproductive health care services and identify the prevalence rate and contraceptive methods of this population. Methods: Data on contraceptive use were collected around the time of the postpartum OB visit for participants in the MOTHER (MaternalOpioidTreatment:HumanExperimentalResearch) study for this secondary analysis. Results: Among the 175 MOTHER participants, data about contraceptivemethodwereonlyavailable for43% (n=76)of the sample andmany reported not attending their postpartumOBvisit. Among those with data, 45% of participants (n=34) reported not using any contraception. Among those reporting contraceptive use, methods included Depo-Provera shots (13%; n=10), oral contraceptives (12%; n=9), IUDs (12%; n=9), tubal ligations (9%; n=7), condom use (8%; n=6), and natural family planning (1%; n=1). Conclusions:These results suggestopioid-maintainedpregnant women frequently utilize postpartum reproductive health services inadequately and indicate current strategies to address their reproductive health needs may not be themost efficacious. Predictors of contraceptive use postpartum need to be identified and treatment strategies revised to support prompt initiation of effective contraception. Due to regulations around opioid maintenance treatment, opioid-maintained women attend their treatment clinic on a regular basis, even early in the postpartum period. This situation may present a unique opportunity to engage opioid-dependent pregnant women about their reproductive health needs, optimize postpartum contraceptive use, and integrate their health care services. Financial support: NIDA T32 DA007242. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.405 Scientific evaluation on substance abuse research through web of science over the 2008–2012 period David Melero-Fuentes1, Remedios Aguilar-Moya2, Juan-Carlos Valderrama-Zurian3, Francisco Bueno-Canigral4, Rafael Aleixandre-Benavent5, Jose-Carlos Perez-de-los-Cobos6 1 INDOTEI, Universidad Catolica de Valencia, Godella, Spain 2 Departamento de Ciencias de la Educacion, Universidad Catolica de Valencia, Godella, Spain 3 Universitat de Valencia, Valencia, Spain 4 Plan Municipal de Drogodependencias, Ayuntamiento de Valencia, Valencia, Spain 5 INGENIO, Spanish Research Council-CSIC, Valencia, Spain 6 Servicio de Psiquiatria, Hospital de la Santa Creu i Santa Pau, Barcelona, Spain Aims: Identify and analyze scientific production and studied drugs on specific and not specific substance abuse journals. Methods: Design of search strategy, treat the bibliographic information, classification of articles regard to drugs studied, bibliometric analysis, identify research groups altogether and by each drug studied was the method used. Results: 44,822 articles have been evaluated, the 26.88% have been published in journals (1.08%) of Web of Science (WoS) Category SubstanceAbuse (CSA),while the rest ofworkswerepublished in 3,382 journals belonging to 95 WoS categories of Health Sciences and Social Sciences. The 67.02% of the articles only study 1 drug; while that alcohol, tobacco and cannabis, and on the other handcocaine andamphetamines are thedrugsmost studied jointly. The 27% of the authors (n=35,223) have published more than 1 paper. Collaborations between 2 or more authors made up 95.18% of documents, with a collaboration index of 5.24. Conclusions: A growth in productivity of scientific research on substance abuse has been identified. The most productive journals that do not belong to WoS CSA accumulate a 0.42% more of papers that these. The multidisciplinary character of this research field is reflected in the wide range of journals as well as the collaboration index and index of transient authors, as has been noted in other studies of Biomedicine andSocial Sciences. AlthoughUSA,UK, Canada and Australia great producers dominate the consolidated research groups, main producers of not English speaking countries of European Union have the highest international collaboration indexes. Financial support: Plan Municipal de Drogodependencias, Ayuntamiento de Valencia, Spain. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.406 Screening and brief intervention for low risk drug use in primary care: A pilot randomized trial Seville Meli1, Tibor Palfai2, Debbie M. Cheng3, D. Alford4, Judith Bernstein1, Jeffrey Samet4, Richard Saitz1 1 Community Health Sciences, Boston University, Boston, MA, United States 2 Psychological and Brain Sciences, Boston University, Boston, MA, United States 3 Biostatistics, Boston University, Boston, MA, United States 4 Medicine, Boston University, Boston, MA, United

A Comparison of Cigarette Smoking Profiles in Opioid-Dependent Pregnant Patients Receiving Methadone or Buprenorphine

Little is known about the relationship between cigarette smoking and agonist treatment in opioid-dependent pregnant patients. The objective of this study is to examine the extent to which cigarette smoking profiles differentially changed during the course of pregnancy in opioid-dependent patients receiving either double-blind methadone or buprenorphine. Patients were participants in the international, randomized controlled Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. A sample of opioid-maintained pregnant patients (18-41 years old) with available smoking data who completed a multisite, double-blind, double-dummy, randomized controlled trial of methadone (n = 67) and buprenorphine (n = 57) between 2005 and 2008. Participants were compared on smoking variables based on opioid agonist treatment condition. Overall, 95% of the sample reported cigarette smoking at treatment entry. Participants in the two medication conditions were similar on pretreatment characteristics including smoking rates and daily cigarette amounts. Over the course of the pregnancy, no meaningful changes in cigarette smoking were observed for either medication condition. The fitted difference in change in adjusted cigarettes per day between the two conditions was small and nonsignificant (β = -0.08, SE = 0.05, p = .132). Results support high rates of smoking with little change during pregnancy among opioid-dependent patients, regardless of the type of agonist medication received. These findings are consistent with evidence that suggests nicotine effects, and interactions may be similar for buprenorphine compared with methadone. The outcomes further highlight that aggressive efforts are needed to reduce/eliminate smoking in opioid-dependent pregnant women.

Nonserious Adverse Events in Randomized Trials with Opioid‐Dependent Pregnant Women: Direct versus Indirect Measurement

How best to measure the occurrence of adverse events during a randomized clinical trial is an issue that has not been adequately examined in the research literature. Focus of this study was on the examination of the relative frequency of occurrence of adverse events directly recorded during the conduct of the trial compared to an indirect determination of adverse events derived from data collected as part of the trial. A secondary analysis of nonserious adverse events that occurred in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) Study was undertaken. MOTHER was a randomized clinical trial of methadone versus buprenorphine in 175 opioid-dependent pregnant women. The two methods of recording adverse events failed to agree on where differences in the frequency of occurrence of adverse events between the medication conditions might exist. Moreover, indirect assessment indicated all participants had experienced at least one adverse event, yet indirect coverage of adverse events was incomplete. Findings suggest indirect examination of occurrence of adverse events should be cautiously undertaken, because indirect assessment of adverse events makes no distinction between what might be simply typical variation in behavior rather than systematic changes in behavior attributable to study condition, and lacks coverage of the full spectrum of adverse events. Contemporaneous direct measurement of adverse events likely yield reasonably valid estimates of the rate of occurrence of the adverse events, while indirect measu-rement of adverse events may not be sufficiently reliable.

Maternal Opioid Treatment: Human Experimental Research (MOTHER)—approach, issues and lessons learned

The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current--and single most comprehensive--research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. The MOTHER study design is outlined, and its basic features are presented. At least seven important lessons have been learned from the MOTHER study: (i) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (ii) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment, patient populations and hospital practices that, in turn, differentially impact recruitment rates, treatment compliance and attrition; (iii) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (iv) staff turnover needs to be addressed with a proactive focus on both hiring and training; (v) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (vi) timely tracking of data in a multi-site trial is both demanding and unforgiving; and (vii) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results.

Neonatal neurobehavior effects following buprenorphine versus methadone exposure.

To determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior. Three sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial participated in this substudy. Medical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria. Thirty-nine full-term infants. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14-15 and 28-30. While neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress-abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over-aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self-regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone-exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self-regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03). While neurobehavior improves during the first month of postnatal life for in utero agonist medication-exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.

Effect of hepatitis C virus status on liver enzymes in opioid‐dependent pregnant women maintained on opioid‐agonist medication

AbstractAimTo examine hepatic enzyme test results throughout the course of pregnancy in women maintained on methadone or buprenorphine.DesignParticipants were randomized to either methadone or buprenorphine maintenance. Blood chemistry tests, including liver transaminases and hepatitis C virus (HCV) status, were determined every 4 weeks and once postpartum. As part of a planned secondary analysis, generalized mixed linear models were conducted with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma‐glutamyl transferase (GGT) as the dependent variables.SettingSix US sites and one European site that provided comprehensive treatment to pregnant opioid‐dependent women.ParticipantsA total of 175 opioid‐dependent pregnant women enrolled in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study.FindingsALT, AST and GGT levels decreased for all subjects across pregnancy trimesters, rising slightly postpartum. HCV‐positive subjects exhibited higher transaminases at all time‐points compared to HCV‐negative subjects, regardless of medication (all Ps &lt; 0.05) condition. Both HCV‐positive and negative buprenorphine‐maintained participants exhibited lower GGT levels than those who were methadone‐maintained (P &lt; 0.05).ConclusionsNeither methadone nor buprenorphine appear to have adverse hepatic effects in the treatment of pregnant opioid‐dependent women.

Fetal assessment before and after dosing with buprenorphine or methadone

To determine pre- and post-dosing effects of prenatal methadone compared to buprenorphine on fetal wellbeing. A secondary analysis of data derived from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial. Six United States sites and one European site that provided comprehensive opioid-dependence treatment to pregnant women. Eighty-one of the 131 opioid-dependent pregnant women completing the MOTHER clinical trial, assessed between 31 and 33 weeks of gestation. Two fetal assessments were conducted, once before and once after study medication dosing. Measures included mean fetal heart rate (FHR), number of FHR accelerations, FHR reactivity in the fetal non-stress test (NST) and biophysical profile (BPP) score. Significant group differences were found for number of FHR accelerations, non-reactive NST and BPP scores (all Ps < 0.05). There were no significant group differences before time of dosing. Significant decreases (all Ps < 0.05) occurred from pre- to post-dose assessment for mean FHR, FHR accelerations, reactive NST and fetal movement. The decrease in accelerations and reactive NST were significant only for fetuses in the methadone group, and this resulted in a significantly lower likelihood of a reactive NST compared to fetuses in the buprenorphine group. Buprenorphine compared with methadone appears to result in less suppression of mean fetal heart rate, fetal heart rate reactivity and the biophysical profile score after medication dosing and these findings provide support for the relative safety of buprenorphine when fetal indices are considered as part of the complete risk-benefit ratio.

Infections and obstetric outcomes in opioid-dependent pregnant women maintained on methadone or buprenorphine.

To characterize infections and compare obstetric outcomes in opioid-dependent pregnant women who participated in a randomized clinical trial comparing agonist medications, methadone and buprenorphine. Incidence of infections was identified as part of the screening medical assessment. As part of a planned secondary analysis, analysis of variance and polytomous logistic regressions were conducted on obstetric outcome variables using treatment randomization condition (maternal maintenance with either methadone or buprenorphine) as the predictor variable, controlling for differences between study sites. Six United States sites and one European site that provided comprehensive treatment to opioid-dependent pregnant women. Pregnant opioid-dependent women (n = 131) who delivered while participating in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. Obstetric, infectious and other maternal medical complications captured by medical records, physical examination, blood tests and self-report. Neonatal medical complications captured by medical records. Hepatitis C was the most common infection (32.3%), followed by hepatitis B (7.6%) and chlamydia (6.1%) among participants at study enrollment. Maternal methadone versus buprenorphine maintenance was associated with a higher incidence of preterm labor (P = 0.04) and a significantly higher percentage of signs of respiratory distress in neonates at delivery (P = 0.05). Other medical and obstetric complications were infrequent in the total sample, as well as in both methadone and buprenorphine conditions. Buprenorphine appears to have an acceptable safety profile for use during pregnancy.

Comparing methadone and buprenorphine maintenance with methadone-assisted withdrawal for the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes

Pregnancy can motivate opioid-dependent women to seek substance abuse treatment. Research has demonstrated that although prenatal exposure to buprenorphine results in less severe neonatal abstinence syndrome (NAS) relative to prenatal methadone exposure, the maternal and other neonatal outcomes are similar for the two medications. Maternal and neonatal outcomes for opioid-dependent pregnant women receiving these medications have not been systematically ompared with methadone-assisted withdrawal. The present study provides an initial assessment of the relative efficacy of both methadone and buprenorphine maintenance versus methadone-assisted withdrawal in terms of neonatal and maternal delivery outcomes. Data were derived from (1) the MOTHER (Maternal Opioid Treatment: Human Experimental Research) study at the Johns Hopkins University Bayview Medical Center (JHBMC), or (2) retrospective records review of women who underwent methadone-assisted withdrawal at the JHBMC during the time period in which participants were enrolled in the MOTHER study. Compared with the methadone maintenance group, the methadone-assisted withdrawal group had a significantly lower mean NAS peak score (Means = 13.7 vs 7.0; P = 0.002), required a significantly lower mean amount of morphine to treat NAS (Means = 82.8 vs 0.2; P < 0.001), had significantly fewer days medicated for NAS (Means = 31.5 vs 3.9; P < 0.001), and remained in the hospital for a significantly fewer number of days, on average (Means = 24.2 vs 7.0; P < 0.019). Compared with the buprenorphine maintenance group, the methadone-assisted withdrawal group required a significantly lower mean amount of morphine to treat NAS (Means = 8.2 vs 0.2; P < 0.001) and significantly fewer days medicated for NAS (Means = 12.0 vs 3.9; P = 0.008). Findings suggest that it is possible for some opioid-dependent pregnant women to succeed with methadone-assisted withdrawal. Future research needs to more fully evaluate the potential benefits and risks of methadone-assisted withdrawal for the maternal-fetal dyad.

Randomized controlled trials in pregnancy: scientific and ethical aspects. Exposure to different opioid medications during pregnancy in an intra‐individual comparison

Chronic medical conditions such as opioid dependence require evidence-based treatment recommendations. However, pregnant women are under-represented in clinical trials. We describe the first within-subject comparison of maternal and neonatal outcomes for methadone- versus buprenorphine-exposed pregnancies. Although methadone is the established treatment of pregnant opioid-dependent women, recent investigations have shown a trend for a milder neonatal abstinence syndrome (NAS) under buprenorphine. However, it is not only the choice of maintenance medication that determines the occurrence of NAS; other factors such as maternal metabolism, illicit substance abuse and nicotine consumption also influence its severity and duration and represent confounding factors in the assessment of randomized clinical trials. CASE SERIES DESCRIPTION: Three women who were part of the European cohort of a randomized, double-blind multi-center trial with a contingency management tool [the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study], each had two consecutive pregnancies and were maintained on either methadone or buprenorphine for their first and then the respective opposite, still-blinded medication for their second pregnancy. Birth measurements, the total neonatal abstinence score, the total amounts of medication used to treat NAS and the days of NAS treatment duration were assessed. Both medications were effective and safe in reducing illicit opioid relapse and avoiding preterm labor. Methadone maintenance yielded to a significantly higher neonatal birth weight. Data patterns suggest that buprenorphine exposure was associated with lower neonatal abstinence syndrome (NAS) scores. Findings from this unique case series are consistent with earlier reports using between-group analyses. Buprenorphine has the potential to become an established treatment alternative to methadone for pregnant opioid-dependent women. Under special consideration of ethical boundaries, psychopharmacological treatment during pregnancy must be addressed as an integral part of clinical research projects in order to optimize treatment for women and neonates.

Smoking in Pregnant Women Screened for an Opioid Agonist Medication Study Compared to Related Pregnant and Non-Pregnant Patient Samples

Background: Little is known about the prevalence and severity of smoking in pregnant opioid dependent patients. Objectives: To first characterize the prevalence and severity of smoking in pregnant patients screened for a randomized controlled trial, Maternal Opioid Treatment: Human Experimental Research (MOTHER), comparing two agonist medications; and second, to compare the MOTHER screening sample to published samples of other pregnant and/or patients with substances use disorders. Methods: Pregnant women (N = 108) screened for entry into an agonist medication comparison study were retrospectively compared on smoking variables to samples of pregnant methadone-maintained patients (N = 50), pregnant opioid or cocaine dependent patients (N = 240), non-pregnant methadone-maintained women (N = 75), and pregnant non-drug-addicted patients (N = 1,516). Results: Of screened patients, 88% (n = 95) smoked for a mean of 140 months (SD = 79.0) starting at a mean age of 14 (SD = 3.5). This rate was similar to substance use disordered patients and significantly higher compared to general pregnant patients (88% vs. 22%, p < .001). Conclusion and Scientific Significance: Aggressive efforts are needed to reduce/eliminate smoking in substance-abusing pregnant women.

Treatment of opioid-dependent pregnant women: Clinical and research issues

This article addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance, based on both research evidence and the collective clinical experience of the authors, which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, is provided to aid clinical decision making. The MOTHER project is a double-blind, double-dummy, flexible-dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the treatment of opioid dependence in pregnant women and their neonates. The article begins with a discussion of appropriate assessment during pregnancy and then addresses clinical management stages including maintenance medication selection, induction, and stabilization; opioid agonist medication management before, during, and after delivery; pain management; breast-feeding; and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed.