Amber M. Holbrook

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. MEASUREMENTS Generalized linear modeling was performed using maternal and infant characteristics to predict: peak NAS score prior to treatment, whether an infant required NAS treatment, length of NAS treatment and total dose of morphine required for treatment of NAS symptoms. FINDINGS Of the sample, 53% (68 infants) required treatment for NAS. Lower maternal weight at delivery, later estimated gestational age (EGA), maternal use of selective serotonin re-uptake inhibitors (SSRIs), vaginal delivery and higher infant birthweight predicted higher peak NAS scores. Higher infant birthweight and greater maternal nicotine use at delivery predicted receipt of NAS treatment for infants. Maternal use of SSRIs, higher nicotine use and fewer days of study medication received also predicted total dose of medication required to treat NAS symptoms. No variables predicted length of treatment for NAS. CONCLUSIONS Maternal weight at delivery, estimated gestational age, infant birthweight, delivery type, maternal nicotine use and days of maternal study medication received and the use of psychotropic medications in pregnancy may play a role in the expression of neonatal abstinence syndrome severity in infants exposed to either methadone or buprenorphine.

Gender and NAS: Does sex matter?

BACKGROUND Neonatal abstinence syndrome (NAS) is a constellation of symptoms resulting from in utero exposure to opioids that appears in 30-80% of opioid exposed infants. Variability in NAS symtomatology is not well understood, and recently it has been suggested that the sex of the infant may play a role in predicting NAS severity. The current study examines the relationship of sex to need for NAS treatment, length of NAS treatment, and peak dose of medication required to treat NAS symptoms. METHODS Retrospective chart review of 308 infants was conducted to determine whether significant differences exist between male and female neonates in need for NAS treatment, length of treatment and peak dose of medication required. Chi-square, multiple ordinary least squares regression, and analysis of variance (ANOVA) analyses were conducted. RESULTS No significant differences were found in need for NAS treatment, length of treatment or peak dose of medication required between male and female neonates. CONCLUSIONS Results suggest that no significant differences exist in NAS severity between male and female infants.

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. SETTING Six United States sites and one European site that provided comprehensive treatment to opioid-dependent pregnant women. PARTICIPANTS Pregnant opioid-dependent women (n = 131) who delivered while participating in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. MEASUREMENTS 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. FINDINGS 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. CONCLUSIONS Buprenorphine appears to have an acceptable safety profile for use during pregnancy.

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. 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. SETTING Six US sites and one European site that provided comprehensive treatment to pregnant opioid-dependent women. PARTICIPANTS A total of 175 opioid-dependent pregnant women enrolled in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. FINDINGS ALT, 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 < 0.05) condition. Both HCV-positive and negative buprenorphine-maintained participants exhibited lower GGT levels than those who were methadone-maintained (P < 0.05). CONCLUSIONS Neither methadone nor buprenorphine appear to have adverse hepatic effects in the treatment of pregnant opioid-dependent women.

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. ANOVA analyses were conducted to determine differences between mean peak CINA scores by medication and completion status. General linear mixed models were fitted to compare trajectories of CINA scores between methadone and buprenorphine conditions, and between study dropouts and completers within the buprenorphine condition. RESULTS Both buprenorphine and methadone patients experienced withdrawal categorized as minimal by the CINA scoring system. Significant differences in mean peak CINA scores for the first 72 hours of induction were found between the methadone (4.5; SD=0.4) and buprenorphine conditions (6.9; SD=0.4), with buprenorphine patients exhibiting higher mean peak CINA scores [F (3, 165)=9.70, p<0.001]. The trajectory of CINA scores showed buprenorphine patients exhibiting a sharper increase in mean CINA scores than methadone patients [F (1, 233)=8.70, p=0.004]. There were no differences in mean peak CINA scores [F (3, 77)=0.08, p=0.52] or in trajectory of CINA scores [F (1, 166)=0.42, p=0.52] between buprenorphine study dropouts and completers. CONCLUSION While mean peak CINA score was significantly higher in the buprenorphine condition than the methadone condition, neither medication condition experienced substantial withdrawal symptoms. Further research on factors related to successful induction to buprenorphine treatment in pregnant women is needed.

Co-occurring psychiatric symptoms in opioid-dependent women: the prevalence of antenatal and postnatal depression.

Background: Despite the high prevalence of psychiatric symptoms in substance-dependent women, little evidence is available on postpartum depression in this population. Objectives: To determine whether demographic variables and prenatal depression predict postpartum depression and select substance abuse treatment outcomes in a sample of pregnant women. Methods: A retrospective chart review was conducted on 125 pregnant women enrolled in a comprehensive substance abuse treatment program. Data on demographic variables, prenatal care attendance, urine drug screen (UDS) results, and psychiatric symptoms were abstracted from patient medical and substance abuse treatment charts. The Postpartum Depression Screening Scale (PDSS) was administered 6 weeks post-delivery. Multiple linear regression was conducted to identify predictors of prenatal care attendance and total PDSS scores at 6 weeks postpartum. Multiple logistic regression was used to examine predictors of positive UDS at delivery. Results: Nearly one-third (30.4%) of the sample screened positive for moderate or severe depression at treatment entry. Psychiatric symptoms did not predict either prenatal care compliance or UDS results at delivery. Almost half of the sample (43.7%) exhibited postpartum depression at 6 weeks post-delivery. No demographic variables correlated with incidence of postnatal depression. Only antenatal depression at treatment entry predicted PDSS scores. Conclusion: Prevalence of antenatal psychiatric disorders and postpartum depression was high in this sample of women seeking substance abuse treatment. Results support prior history of depression as a predictor of risk for developing postpartum depression. Scientific Significance: Routine screening for perinatal and postpartum depression is indicated for women diagnosed with substance abuse disorders.

Effectiveness of a Smoking Cessation Intervention for Methadone-Maintained Women: A Comparison of Pregnant and Parenting Women

Women in substance abuse programs have high rates of smoking. Pregnancy represents a unique opportunity for intervention, but few data exist to guide tailoring of effective interventions. In this study, 44 pregnant and 47 nonpregnant opioid-dependent women enrolled in comprehensive substance abuse treatment received a 6-week smoking cessation intervention based on the 5As counseling model. The number of daily cigarettes decreased by 49% for pregnant patients and 32% for nonpregnant patients at the 3-month followup. Length of time in substance abuse treatment did not correlate with smoking cessation or reduction for either group. Factors predicting reduction of cigarette smoking differed for pregnant versus nonpregnant patients. For pregnant patients, lower levels of nicotine use prior to intervention and self-reported cigarette cravings predicted successful reduction in smoking. For nonpregnant patients, lower affiliative attachment to cigarettes, reliance on cigarettes for cognitive enhancement, and greater sense of control predicted more successful outcomes.

Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma.

Abstract The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States.

Medication-Assisted Treatment for Pregnant Women: A Systematic Review of the Evidence and Implications for Social Work Practice

Evidence-based practice with pregnant clients who are opioid-dependent can be especially challenging because pregnant women are rarely included in clinical trials. The paper synthesizes systematic reviews on the outcomes of medication-assisted treatment for opioid dependent pregnant women and compares the effectiveness of methadone and buprenorphine. We explore evidence on maternal and neonatal outcomes, the safety of breastfeeding, and discuss the implications for social work practice. Searches were conducted in 6 databases. Ten reviews met the inclusion criteria. Results suggest medication-assisted treatment with either methadone or buprenorphine are equally effective in reducing maternal substance use, although methadone may offer slightly higher treatment retention rates when flexible dosing is implemented. Physical parameters and Apgar scores at birth show no significant differences in neonates exposed to methadone versus buprenorphine. Rates of treatment for neonatal abstinence syndrome also do not differ. However, when treatment is required burprenorphine may produce a shorter duration of withdrawal. Data on long-term developmental outcomes following in-utero exposure to opioid maintenance medications is inconclusive. Results suggest that there is minimal transmission of either methadone or buprenorphine to the neonate in breast milk. Conclusions are limited by missing data on broader psychosocial and maternal health outcomes. Evidence on long-term developmental outcomes for neonates is also confounded by prenatal drug exposure and environmental factors. Social workers engage with opioid-dependent pregnant women in many settings and can play an important role in ensuring access to treatment, and in addressing misconceptions around medication-assisted treatment for pregnant women with family members, peer supports, and other health care providers.

Implementation of Dialectical Behavior Therapy in Residential Treatment Programs: A Process Evaluation Model for a Community-Based Agency

Dialectical behavior therapy (DBT) can be challenging to implement in community-based settings. Little guidance is available on models to evaluate the effectiveness or sustainability of training and implementation efforts. Residential programs have much to gain from introduction of evidence-based practices, but present their own challenges in implementation. This paper presents a low-cost process evaluation model to assess DBT training piloted in residential programs. The model targets staff and organizational factors associated with successful implementation of evidence-based practices and matches data collection to the four stages of the DBT training model. The strengths and limitations of the evaluation model are discussed.