Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement.

Background And Objectives: 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.

Methods: A secondary analysis of nonserious adverse events that occurred in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) Study was undertaken.

Induction of pregnant women onto opioid-agonist maintenance medication: an analysis of withdrawal symptoms and study retention.

Background: Induction onto buprenorphine during pregnancy may be more challenging than induction onto methadone. This study explores factors predicting withdrawal intensities and compares trajectories of withdrawal during the induction phase between opioid-dependent women randomly assigned to methadone or buprenorphine.

Methods: A secondary analysis was conducted on data from 175 opioid-dependent pregnant women inducted onto buprenorphine or methadone subsequent to stabilization on morphine sulfate.

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

Aim: To examine hepatic enzyme test results throughout the course of pregnancy in women maintained on methadone or buprenorphine.

Design: Participants 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.

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

Aims: 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.

Design: 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.

Opioid dependence during pregnancy: relationships of anxiety and depression symptoms to treatment outcomes.

Aims: To examine the relationship of anxiety and depression symptoms with treatment outcomes (treatment discontinuation, rates of ongoing use of illicit drugs and likelihood of preterm delivery) in opioid-dependent pregnant women and describe their use of psychotropic medications.

Design And Setting: Secondary data analysis from a randomized clinical trial of treatment for opioid dependence during pregnancy.

Participants: A total of 175 opioid-dependent pregnant women, of whom 131 completed treatment.

Differences in the profile of neonatal abstinence syndrome signs in methadone- versus buprenorphine-exposed neonates.

Aims: To compare the profile of signs of neonatal abstinence syndrome (NAS) in methadone- versus buprenorphine-exposed infants.

Design, Setting And Participants: Secondary analysis of NAS data from a multi-site, double-blind, double-dummy, flexible-dosing, randomized clinical trial. Data from a total of 129 neonates born to opioid-dependent women who had been assigned to receive methadone or buprenorphine treatment during pregnancy were examined.

Predicting treatment for neonatal abstinence syndrome in infants born to women maintained on opioid agonist medication.

Aim: To identify factors that predict the expression of neonatal abstinence syndrome (NAS) in infants exposed to methadone or buprenorphine in utero.

Design And Setting: Multi-site randomized clinical trial in which infants were observed for a minimum of 10 days following birth, and assessed for NAS symptoms by trained raters.

Participants: A total of 131 infants born to opioid dependent mothers, 129 of whom were available for NAS assessment.

Fetal assessment before and after dosing with buprenorphine or methadone.

Aim: To determine pre- and post-dosing effects of prenatal methadone compared to buprenorphine on fetal wellbeing.

Design: A secondary analysis of data derived from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial.

Setting: Six United States sites and one European site that provided comprehensive opioid-dependence treatment to pregnant women.

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

Aims: 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.

Methods: The MOTHER study design is outlined, and its basic features are presented.

Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review.

Aims: This paper reviews the published literature regarding outcomes following maternal treatment with buprenorphine in five areas: maternal efficacy, fetal effects, neonatal effects, effects on breast milk and longer-term developmental effects.

Methods: Within each outcome area, findings are summarized first for the three randomized clinical trials and then for the 44 non-randomized studies (i.e.

Cigarette Smoking and Neonatal Outcomes in Depressed and Non-Depressed Opioid-Dependent Agonist-Maintained Pregnant Patients.

AIMS: To investigate whether cigarette smoking and/or depression contribute to neonatal abstinence syndrome (NAS) severity. DESIGN: Cohort study analyzing data from a randomized, controlled trial of methadone versus buprenorphine. SETTING: Seven study sites that randomized patients to study conditions and provided comprehensive addiction treatment to pregnant patients.

Neonatal abstinence syndrome after methadone or buprenorphine exposure.

Background: Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.

Co-occurring psychiatric symptoms are associated with increased psychological, social, and medical impairment in opioid dependent pregnant women.

The interaction of psychiatric symptoms with drug dependence during pregnancy is not well understood. This study examines the relationship of psychiatric symptoms to severity of drug use and drug-related problems among participants in a clinical trial of pharmacologic treatment of opioid dependence during pregnancy (N = 174). A total of 64.

Characteristics of opioid-using pregnant women who accept or refuse participation in a clinical trial: screening results from the MOTHER study.

Background: Although concerns arise about the generalizability of results from Randomized Controlled Trials (RCTs), few studies systematically examine this issue.

Objectives: This study compared the characteristics of 427 opioid-using pregnant women who did (n = 208) and did not consent (n = 219) to enrollment in a multicenter clinical trial of agonist medications (i.e.

Psychopharmacologic management of opioid-dependent women during pregnancy.

Illicit drug use during pregnancy presents complex clinical challenges, including reducing drug use and treating psychiatric disorders. Pharmacologic treatment of psychiatric disorders in a pregnant woman requires an evaluation of the balance between potential clinical benefit and the risk of potential neonatal consequences. This study describes psychiatric symptoms in 111 opioid-dependent pregnant women and their prescribed psychotropic medications.

Motivation Enhancement Therapy with pregnant substance-abusing women: does baseline motivation moderate efficacy?

Some evidence suggests that motivational approaches are less efficacious--or even counter-productive--with persons who are relatively motivated at baseline. The present study was conducted to examine whether disordinal moderation by baseline motivation could partially explain negative findings in a previous study [Winhusen, T., Kropp, F.

Predictors of outcome for short-term medically supervised opioid withdrawal during a randomized, multicenter trial of buprenorphine-naloxone and clonidine in the NIDA clinical trials network drug and alcohol dependence.

Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid-dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting.

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.

Efficacy of dose and contingency management procedures in LAAM-maintained cocaine-dependent patients.

Opioid- and cocaine-dependent participants (N=140) were randomly assigned to one of the following in a 12-week clinical trial: LAAM (30, 30, 39 mg/MWF) with contingency management (CM) procedures (LC); LAAM (30, 30, 39 mg/MWF) without CM (LY); LAAM (100, 100, 130 mg/MWF) with CM (HC); LAAM (100, 100, 130 mg/MWF) without CM (HY). Urine samples were collected thrice-weekly. In CM, each urine negative for both opioids and cocaine resulted in a voucher worth a certain monetary value that increased for consecutively drug-free urines.

Transferring methadone-maintained outpatients to the buprenorphine sublingual tablet: a preliminary study.

There is no accepted algorithm to transfer opioid-dependent patients from methadone (METH) to its new alternative, buprenorphine (BUP). Five outpatients transferred (double blind, double dummy) from METH 60 mg/day (with one day at 45 mg) to BUP 8 mg s.l.

Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients.

Background: Alteration in noradrenergic regulation as well as alteration in the hypothalamic-pituitary-adrenal (HPA) axis have been associated with opioid dependence and acute abstinence symptoms.

Methods: This double-blind, placebo-controlled study evaluated subjective, physiologic, and biochemical responses to yohimbine (.4 mg/kg, IV) in eight patients receiving methadone and compared results to those from a pool of nine healthy volunteers.