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

ABSTRACT: 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.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.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.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.

SUBMITTER: Holbrook AM

PROVIDER: S-EPMC3732530 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

Holbrook Amber M AM Jones Hendree E HE Heil Sarah H SH Martin Peter R PR Stine Susan M SM Fischer Gabriele G Coyle Mara G MG Kaltenbach Karol K

Drug and alcohol dependence 20130321 1-2

<h4>Background</h4>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.<h4>Methods</h4>A secondary analysis was conducted on data from 175 opioid-dependent pregnant women inducted onto buprenorphine or methadone subsequent to stabilization on ...[more]

PMID: 23523131

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Project description:Newborns exposed to prenatal opioids often experience intense postnatal withdrawal after cessation of the opioid, called neonatal opioid withdrawal syndrome (NOWS), with limited pre- and postnatal therapeutic options available. In a prior study in pregnant mice we demonstrated that the peripherally selective opioid antagonist, 6β-naltrexol (6BN), is a promising drug candidate for preventive prenatal treatment of NOWS, and a therapeutic mechanism was proposed based on preferential delivery of 6BN to fetal brain with relative exclusion from maternal brain. Here, we have developed methadone (MTD) treated pregnant guinea pigs as a physiologically more suitable model, enabling detection of robust spontaneous neonatal withdrawal. Prenatal MTD significantly aggravates two classic maternal separation stress behaviors in newborn guinea pigs: calling (vocalizing) and searching (locomotion) - natural attachment behaviors thought to be controlled by the endogenous opioid system. In addition, prenatal MTD significantly increases the levels of plasma cortisol in newborns, showing that cessation of MTD at birth engages the hypothalamic-pituitary-adrenal (HPA) axis. We find that co-administration of 6BN with MTD prevents these withdrawal symptoms in newborn pups with extreme potency (ID50 ∼0.02 mg/kg), at doses unlikely to induce maternal or fetal withdrawal or to interfere with opioid antinociception based on many prior studies in rodents and non-human primates. Furthermore, we demonstrate a similarly high potency of 6BN in preventing opioid withdrawal in adult guinea pigs (ID50 = 0.01 mg/kg). This high potency appears to run counter to our pharmacokinetic studies showing slow 6BN transit of both the placenta and maternal blood brain barrier in guinea pigs, and calls into question the preferential delivery mechanism. Rather, it suggests a novel receptor mechanism to account for the selectively high potency of 6BN to suppress opioid dependence at all developmental stages, even in adults, as compared to its well-established low potency as a classical opioid antagonist. In conclusion, 6BN is an attractive compound for development of a preventive therapy for NOWS.

Project description:?(9)-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB(1) and CB(2) cannabinoid receptors, the role these receptors play in reducing the variety of opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this study was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models of opioid dependence. Morphine-dependent mice challenged with naloxone reliably displayed a profound withdrawal syndrome, consisting of jumping, paw tremors, diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose dependently reduced the intensity of most measures through the activation of CB(1) receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine-dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5-(trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845) reduced the intensity of naloxone-precipitated jumps and paw flutters through the activation of CB(1) receptors but did not ameliorate incidence of diarrhea or weight loss. In the final series of experiments, we investigated whether JZL184 or PF-3845 would attenuate naloxone-precipitated contractions in morphine-dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone-induced contractions, although this model does not account mechanistically for the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These results indicate that endocannabinoid catabolic enzymes are promising targets to treat opioid dependence.

Project description:BackgroundRetention in care is a prerequisite for successful recovery, especially for a chronic condition like opioid dependence. Though retention varies greatly depending on the different substitution medication and treatment model, treatment retention is used as an indicator of treatment quality and effectiveness of care on a system and individual level. To monitor the overall quality of the Austrian opioid agonist treatment (OAT) system and to monitor patient satisfaction within the system, a new online-based registry called "eSuchmittel" was introduced in Austria at the beginning of 2011. The objective of this study is to analyze retention rates within the Austrian treatment system and to identify patient characteristics associated with retention, using data collected by the substitution registry.MethodsThe complete Austrian sample of 4778 registered patients starting treatment between 1.1.2011 to 31.12.2012 were included in the prospective cohort study using data from the Austrian substitution registry. For the statistical analysis, multivariate Cox Regression and Kaplan-Meier survival analysis were used to evaluate retention in treatment.ResultsThe retention rate of the total cohort after two years was around 61%. Retention rates were significantly lower for men (exp(B) = .806, 95% CI 0.714-0.908) and significantly higher for patients aged 30 and older (exp(B) = 1.155, 95% CI 1.044-1.279), among patients located in Vienna (exp(B) = 1.439, 95% CI 1.273-1.626) and among patients prescribed oral slow-release morphine (SROM) (exp(B) = 2.141, 95% CI 1.885-2.430).ConclusionsAverage retention in the Austrian system is high in comparison to international retention rates. Nationally, SROM demonstrates higher treatment retention when compared to other available substitution medications. Sociodemographic and regional indicators also contribute to higher retention in care. A systematic monitoring of retention rates within a national registry is an important tool helping to evaluate the quality of care. In this study, the Austrian OAT system proves very high retention in care, an important success criterion.

Project description:BACKGROUND AND AIMS:Cannabis use is common among people on opioid agonist treatment (OAT), causing concern for some care providers. However, there is limited and conflicting evidence on the impact of cannabis use on OAT outcomes. Given the critical role of retention in OAT in reducing opioid-related morbidity and mortality, we aimed to estimate the association of at least daily cannabis use on the likelihood of retention in treatment among people initiating OAT. As a secondary aim we tested the impacts of less frequent cannabis use. DESIGN:Data were drawn from two community-recruited prospective cohorts of people who use illicit drugs (PWUD). Participants were followed for a median of 81 months (interquartile range = 37-130). SETTING:Vancouver, Canada. PARTICIPANTS:This study comprised a total of 820 PWUD (57.8% men, 59.4% of Caucasian ethnicity, 32.2% HIV-positive) initiating OAT between December 1996 and May 2016. The proportion of women was higher among HIV-negative participants, with no other significant differences. MEASUREMENTS:The primary outcome was retention in OAT, defined as remaining in OAT (methadone or buprenorphine/naloxone-based) for two consecutive 6-month follow-up periods. The primary explanatory variable was cannabis use (at least daily versus less than daily) during the same 6-month period. Confounders assessed included: socio-demographic characteristics, substance use patterns and social-structural exposures. FINDINGS:In adjusted analysis, at least daily cannabis use was positively associated with retention in OAT [adjusted odds ratio (aOR) = 1.21, 95% confidence interval (CI) = 1.04-1.41]. Our secondary analysis showed that compared with non-cannabis users, at least daily users had increased odds of retention in OAT (aOR = 1.20, 95% CI = 1.02-1.43), but not less than daily users (aOR = 1.00, 95% CI = 0.87-1.14). CONCLUSIONS:Among people who use illicit drugs initiating opioid agonist treatment in Vancouver, at least daily cannabis use was associated with approximately 21% greater odds of retention in treatment compared with less than daily consumption.

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

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

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