Children had increased risks of impaired motor and visual-motor skills after prenatal exposure to opioid maintenance therapy.

AIM: Preschool children prenatally exposed to opioid maintenance therapy (OMT) have an increased risk of neurodevelopmental impairments. We aimed to investigate long-term motor and visual-motor integration outcome in children aged 5-13 Years, born to mothers in OMT. METHODS: From January 2018 to June 2021, 63 children prenatally exposed to OMT and 63 comparison children matched for age and gender, were examined at two Norwegian hospitals. Motor skills were assessed by the Movement-ABC test and visual-motor integration by the Beery VMI test. A motor function neurological assessment test was used to examine neuromotor soft signs. RESULTS: In the OMT-exposed group, 16% had motor impairment, 35% had motor problems and 19% had visual-motor integration problems. Forty-three percent of the exposed children had neuromotor soft signs. Strabismus had some influence on motor and visual-motor outcomes but could not explain the group differences. CONCLUSION: Children prenatally exposed to opioid maintenance therapy have an increased risk of long-term motor impairment and visual-motor problems. In addition, they exhibit significantly more neuromotor soft signs, which may affect general well-being, leisure activities and school performance.

Blended smartphone intervention for patients in opioid maintenance treatment in Iran: protocol for a randomized controlled trial.

BACKGROUND: The pattern of substance use in Iran is characterized by a high prevalence of opioid use and opioid use disorder (OUD). Although opioid maintenance therapy (OMT) has been introduced in Iran, approximately 50% of people with opioid use disorder remain unreached. Moreover, psychosocial treatment of OUD and common mental health symptoms during OMT is limited. Digital interventions have been shown to improve psychological distress, depression, anxiety, and post-traumatic stress disorder symptoms. In addition, providing psychoeducation and risk reduction counseling to prevent communicable diseases like HIV and infectious hepatitis is common via the Internet. However, despite these promising advances, no smartphone intervention in OMT has been investigated for the treatment of OUD and common comorbid mental health symptoms. OBJECTIVE: We examine the effectiveness of adding a blended smartphone intervention based on community reinforcement approach, motivational interviewing- and cognitive behavioral therapy compared to OMT as usual that aims to improve OMT outcomes and addresses common mental health symptoms in OMT patients in Iran. METHOD: Adults with opioid dependence entering 8 treatment centers in Tehran, Iran will be randomly assigned to receive either OMT plus a smartphone intervention or OMT as usual. The primary outcomes will be the percentage of negative urine tests for illicit, non-prescribed use of opioids (opium, heroin, tramadol) and treatment retention. Secondary outcomes will include the longest period of abstinence from the illicit, non-prescribed use of opioids (opium, heroin, and tramadol) confirmed by urine samples, changes in communicable disease risk-taking behaviors, changes in stress and common mental health symptoms, and client satisfaction. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models. DISCUSSION: This study will provide substantial knowledge for designing effective blended interventions for OUD. Moreover, it will investigate if treatment retention and OMT-related outcomes and common mental health symptoms can be improved by adding a smartphone intervention to OMT. TRIAL REGISTRATION: https://en.irct.ir/trial/53578 .

Buprenorphine-cannabis interaction in patients undergoing opioid maintenance therapy.

Buprenorphine is a partial µ-opioid agonist widely used for opioid maintenance therapy (OMT). It is mainly metabolized to pharmacologically active norbuprenorphine by the cytochrome P450 (CYP) isozyme 3A4. This may give rise to drug-drug interactions under combinations with inhibitors or inducers of CYP3A4. Cannabis is a potential inhibitor of CYP3A4, and there is a large degree of concomitant cannabis use among OMT patients. We performed a retrospective analysis on liver healthy OMT patients substituted with buprenorphine, either with (n = 15) or without (n = 17) concomitant use of cannabis. Patients with additional illicit drugs or medications affecting CYP3A were excluded. Measured blood concentrations of buprenorphine and norbuprenorphine were compared between the two groups. Cannabis users and non-users received similar doses, but users had 2.7-fold higher concentrations of buprenorphine (p < 0.01) and 1.4-fold for norbuprenorphine (1.4-fold, p = 0.07). Moreover, the metabolite-to-parent drug ratio was 0.98 in non-users and 0.38 in users (p = 0.02). Female gender did not produce significant effects. These findings indicate that cannabis use decreases the formation of norbuprenorphine and elevates buprenorphine and norbuprenorphine concentrations in blood most probably by inhibition of CYP3A4. The pharmacokinetic interaction may give rise to enhanced or altered opioid activity and risk of intoxications. Physicians should inform patients about this risk and supervise cannabis users by regular control of buprenorphine blood levels, i.e., by therapeutic drug monitoring.

Affective decision-making in children prenatally exposed to opioids.

Although opioid maintenance therapy (OMT) is currently recommended for pregnant opioid-dependent women, potential effects on children's long-term development are still largely unknown. The current study assessed the long-term cognitive development of children born to women in OMT. Particularly, children's decision-making performance was assessed with a child-friendly version of the Iowa Gambling Task. Using a prospective longitudinal design, a cohort of children was followed from birth to middle childhood. Data were collected in Norway between 2005 and 2017. Participants included 41 children (aged 9-11 years), 20 of whom had histories of prenatal methadone or buprenorphine exposure. Background data were collected from personal interviews and medical records in 2005-2006. Children's affective decision-making was assessed in 2016-2017. Results showed no main effect of group on the net scores in the gambling task, F(1, 39) = 1.44, p = 0.24, η2 = 0.04, demonstrating no group differences in decision-making performance. A main effect of group was found on sensitivity to punishment, with children in the control group choosing the doors with the infrequent, but high punishment more often compared to children in the OMT group, F(1, 39) = 4.90, p = 0.03, η2  = 0.11. No main effect of group on decision-making speed was found, although results showed a significant interaction effect between group and gain, F(1, 8,194) = 4.09, p = 0.04, η2  = 0.001. Children prenatally exposed to opioids were found to have normal decision-making performance on an affective decision-making task and were able to consider future consequences when making decisions.

[New slow-release buprenorphine formulations for optimization of opioid substitution]. / Neue Slow-release-Buprenorphinformulierungen zur Optimierung der Opioidsubstitution.

Opioid maintenance treatment with methadone or buprenorphine is an established first-line treatment for opioid dependence. In addition to the novel weekly and monthly subcutaneously injectable buprenorphine depot CAM 2038 (Buvidal®), which is already available in Germany, two other long-acting buprenorphine formulations may be introduced in the near future: the monthly depot formulation RBP-6000 (Sublocade™) and a 6-month buprenorphine depot implant (Probuphine™). Basic pharmacological and clinical data of these three medications are given and possible clinical applications are discussed.

A Systematic, Intensive Statistical Investigation of Data from the Comprehensive Analysis of Reported Drugs (CARD) for Compliance and Illicit Opioid Abstinence in Substance Addiction Treatment with Buprenorphine/naloxone.

BACKGROUND: Buprenorphine and naloxone (bup/nal), a combination partial mu receptor agonist and low-dose delta mu antagonist, is presently recommended and used to treat opioid-use disorder. However, a literature review revealed a paucity of research involving data from urine drug tests that looked at compliance and abstinence in one sample. METHOD: Statistical analysis of data from the Comprehensive Analysis of Reported Drugs (CARD) was used to assess compliance and abstinence during treatment in a large cohort of bup/nal patients attending chemical-dependency programs from eastern USA in 2010 and 2011. RESULTS: Part 1: Bup/nal was present in 93.4% of first (n = 1,282; p <.0001) and 92.4% of last (n = 1,268; p <.0001) urine samples. Concomitantly, unreported illicit drugs were present in 47.7% (n = 655, p =.0261) of samples. Patients who were compliant to the bup/nal prescription were more likely than noncompliant patients to be abstinent during treatment (p =.0012; odds ratio = 1.69 with 95% confidence interval (1.210, 2.354). Part 2: An analysis of all samples collected in 2011 revealed a significant improvement in both compliance (p < 2.2 × 10-16) and abstinence (p < 2.2 × 10-16) during treatment. Conclusion/Importance: While significant use of illicit opioids during treatment with bup/nal is present, improvements in abstinence and high compliance during maintenance-assisted therapy programs may ameliorate fears of diversion in comprehensive programs. Expanded clinical datasets, the treatment modality, location, and year of sampling are important covariates, for further studies. The potential for long-term antireward effects from bup/nal use requires consideration in future investigations.

Delayed villous maturation in term placentas exposed to opioid maintenance therapy: a retrospective cohort study.

BACKGROUND: Opioid use disorder among pregnant women is associated with adverse perinatal outcomes and is increasing in the United States. The standard of care for pregnant women with opioid use disorder is opioid maintenance therapy including either methadone or buprenorphine, which can be initiated at any time during pregnancy. These medications are known to cross the placenta but their placental and fetal effects have not been well characterized. Delayed villous maturation, a placental finding associated with stillbirth, was observed in placentas exposed to opioid maintenance therapy. Given the association of delayed villous maturation with stillbirth, and the possible relationship between opioid maintenance therapy and delayed villous maturation, this study was undertaken to explore the association between opioid maintenance therapy and this placental finding. Delayed villous maturation was not previously reported in placentas exposed to opioids or opioid maintenance therapy. OBJECTIVE: This study sought to compare risk of delayed villous maturation in term placentas exposed and unexposed to opioid maintenance therapy with buprenorphine or methadone. STUDY DESIGN: This was a retrospective cohort study conducted between 2010 through 2012 at Magee-Womens Hospital comparing delayed villous maturation in placentas of women with opioid use disorder exposed to either buprenorphine (n = 86) or methadone (n = 268) versus women without opioid use disorder (n = 978). Potential covariates were assessed in univariate analyses with none significantly associated with delayed villous maturation. The final model used conditional logistic regression adjusting for smoking status alone. RESULTS: Among women without opioid use disorder (and therefore not exposed to opioid maintenance therapy), delayed villous maturation was identified in 5.7% of placentas while the prevalence among women treated with buprenorphine or methadone was 8.1% and 10.8%. Overall, the crude odds of being diagnosed with delayed villous maturation were significantly greater in those exposed to opioid maintenance therapy compared to those not exposed (odds ratio, 1.86; 95% confidence interval, 1.20-2.89). When considered separately, women treated with methadone had significantly greater odds of having a placenta with delayed villous maturation than women without exposure to opioid maintenance therapy (odds ratio, 2.00; 95% confidence interval, 1.52-3.20). Women treated with buprenorphine did not have significantly greater odds of this placental diagnosis when compared to the women unexposed to opioid maintenance therapy (odds ratio, 1.46; 95% confidence interval, 0.64-3.31). Results were similar after accounting for smoking. CONCLUSION: Delayed villous maturation was more common in the placentas of women exposed to opioid maintenance therapy. Further studies are required to characterize rates and extent of delayed villous maturation in the general population as well as to differentiate between possible effects of opioid exposure (eg, heroin, illicit use of prescription opioids) vs those of opioid maintenance therapy (buprenorphine and methadone).

[Maintenance treatment in opioid-dependent patients with migration background]. / Opioidsubstitution bei heroinabhängigen Patienten mit Migrationshintergrund.

BACKGROUND: No regional analyses regarding opioid-dependent patients in maintenance treatment with a migration background have so far been performed in German-speaking countries. OBJECTIVES: This study examined patients with and without a migration background regarding socioeconomic parameters, characteristics of dependency and attitude towards opiate maintenance treatment (OMT). MATERIAL AND METHODS: From May to October 2011 patients in OMT from all of the 20 psychiatry clinics and 110 physician practices in Berlin with a licence to provide OMT were included in this analysis. RESULTS: Out of the 986 participating patients, 956 gave information on migration background and of these, 204 (21.3 %) originated from a country other than Germany. Compared to patients without a migration background, their participation in a maintenance program was significantly shorter and they more often expressed a desire to end OMT and wanted a limited duration of OMT. CONCLUSION: The differences regarding duration of OMT and the wish to end OMT can reflect a stronger desire for abstinence and a different attitude towards maintenance treatment of patients with a migration background.

Visual function in Norwegian children aged 5-13 years with prenatal exposure to opioid maintenance therapy: A case-control study.

PURPOSE: To assess various aspects of visual function in school children prenatally exposed to opioid maintenance therapy (OMT) and to explore possible outcome differences between prenatal methadone and buprenorphine exposure. METHODS: In a cross-sectional case-control study, 63 children aged 5-13 years with prenatal OMT exposure were compared with 63 age- and gender-matched, non-exposed controls regarding important visual parameters, such as visual acuity, orthoptic status, refractive state, colour vision, and visual field. RESULTS: The OMT-exposed children had significantly poorer visual acuity, both for the best eye, the worst eye and binocularly. Two children had mild visual impairment. Manifest strabismus was more frequent in the OMT group, 30%, vs. 4.8% in the control group. The most frequent types of strabismus were accommodative esotropia and intermittent exotropia. Manifest nystagmus was present in 10 (16%) of the exposed children compared to one among the non-exposed children. The accommodative amplitude was decreased in the OMT group compared to the controls. After adjusting for polydrug exposure and SGA (small-for-gestational-age), the between-group differences in visual acuity, strabismus, and nystagmus remained. The methadone-exposed children had poorer visual acuity, increased frequency of strabismus and a higher percentage of nystagmus, hypermetropia and astigmatism compared to the buprenorphine-exposed children. CONCLUSIONS: School-age children exposed to methadone or buprenorphine in utero had a higher prevalence of strabismus and nystagmus, and a lower visual acuity and accommodation amplitude. Buprenorphine exposure was associated with more favourable results than methadone exposure on most visual outcome measures and should be the preferred substance in OMT.

Effects of buprenorphine, methadone, and cariprazine on economic choice between remifentanil and food in squirrel monkeys.

We recently reported an economic choice task in which squirrel monkeys chose between differing amounts of remifentanil, a fast-acting opioid, or a food reward to develop a preclinical screen for evaluating potential pharmacotherapies for opioid dependence. Herein, two known opioid addiction treatments are evaluated using this task, as well as a potential new agent, cariprazine, a dopamine D2/D3 receptor partial agonist currently used to treat bipolar disorder and schizophrenia. Preclinical rodent studies suggest this class of compounds may reduce opiate self-administration. Squirrel monkeys were pretreated daily with clinically relevant doses of each compound during the five days of treatment evaluation using the economic choice task. Shifts in drug preference were measured as changes in subjects' indifference values, where the probability of drug and milk choice are equivalent. Buprenorphine produced a significant shift in indifference value between baseline and treatment weeks, indicating a decrease in drug preference. Subjects treated with methadone and cariprazine did not show any significant shift in drug preference. Differences between the buprenorphine and methadone results likely reflect a lack of opioid dependence in the subjects. The cariprazine results suggest that it does not alter opioid reward in non-dependent primates over a five day period.

Verbal and nonverbal memory in school-aged children born to opioid-dependent mothers.

BACKGROUND: The potential long-term developmental effects of prenatal methadone and buprenorphine exposure during pregnancy are still largely unknown. AIMS: We investigated memory function in school-aged children of women enrolled in opioid maintenance therapy (OMT) during pregnancy. STUDY DESIGN: Prospective longitudinal cohort study. SUBJECTS: Participants included 41 children (aged 9-11 years), 20 of which had histories of prenatal methadone or buprenorphine exposure. OUTCOME MEASURES: Verbal and non-verbal memory function was assessed using four subtests from the Test of Memory and Learning - Second edition (TOMAL-2). RESULTS: The OMT group scored lower on both the two non-verbal as well as the two verbal memory tasks, all p-values <.05. Group differences remained for three out of the four subtests after controlling for general IQ. Including maternal tobacco use during pregnancy increased the explanatory power of the model, R2 change of 0.07, p = .04. CONCLUSIONS: Children prenatally exposed to methadone or buprenorphine had significantly lower memory performance, however, this association may in part be explained by maternal tobacco use during pregnancy. Consequently, smoking cessation programs should be systematically integrated into opioid maintenance therapy programs for pregnant women.

Scoping Review of Barriers and Facilitators of Breastfeeding in Women on Opioid Maintenance Therapy.

OBJECTIVE: To synthesize the literature on the barriers and facilitators of breastfeeding among women on opioid maintenance therapy (OMT) to inform nursing interventions and improve breastfeeding outcomes. DATA SOURCES: We searched 11 databases using the following key terms: breastfeeding, barriers, facilitators, promotion, and opioid. STUDY SELECTION: We included articles published in English since 2015 that addressed barriers and facilitators of breastfeeding in women on OMT. We did not limit our search to specific types of studies. Our search produced 65 records. After reviewing titles and abstracts, we assessed 21 full-text articles and excluded seven for lack of data related to our key terms. As a result, we included five qualitative studies, three reviews, three mixed-methods studies, two retrospective cohort studies, and one case report (14 articles) in our final review. DATA EXTRACTION: We extracted data from each article and sorted them in a table for analysis and synthesis. Data included study purpose, research questions, design and methodology, and findings specifically pertaining to the identification of barriers and facilitators of breastfeeding for women on OMT. DATA SYNTHESIS: We identified three themes related to facilitators of and barriers to breastfeeding: Information, Support, and Health Care System Factors. CONCLUSION: The results of our review suggest that most barriers and facilitators of breastfeeding in women on OMT are manageable with improved health care practices. Primary and acute care health professionals should modify practices to minimize barriers to breastfeeding. Nurses should provide better breastfeeding education and preparation, sensitive care in the immediate postpartum period, and extended follow-up after hospital discharge for women on OMT.

Prenatal exposure to methadone or buprenorphine and long-term outcomes: A meta-analysis.

AIM: To combine meta-analyses of multiple long-term outcomes in children prenatally exposed to methadone or buprenorphine through their mothers' Opioid maintenance therapy (OMT) with a systematic review of similar outcomes in experimental animals. METHOD: The Medline, Embase, Web of Science, CINAHL, Cochrane and Epistemonikos databases were searched through August 30, 2018. Clinical studies measuring effects on cognitive, behavioral or visual outcomes in 3 months or older children prenatally exposed to OMT and control group(s) were included for meta-analyses. Experimental animal studies with similar exposures and outcomes were included in a systematic review. The three authors independently performed abstract screenings and full-text reviews, and extracted the data. One author performed the meta-analyses. RESULTS: The pooled results of the meta-analyses showed worse cognitive, psychomotor, behavioral, attentional and executive functioning, and affected vision in children born to mothers who were in OMT during pregnancy compared to children without prenatal drug exposure (overall effect size = 0.49, 95% confidence interval = 0.38, 0.59, p < 0.00001). Many of the experimental animal studies showed impaired outcomes after prenatal exposure to methadone or buprenorphine. The clinical results may be biased, e.g., with the OMT group having more concurrent risk factors than the unexposed comparison group. There are few studies of older children. CONCLUSION: Children born to mothers in OMT show worse outcomes for a number of different behaviors and impaired vision compared to children born to nonusers. Experimental animal studies indicate that there might be a causal relationship between prenatal methadone or buprenorphine exposure and subsequent negative outcomes.

Pharmacogenomics of methadone: a narrative review of the literature.

Background: Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to manage chronic and acute surgical pain. The variability in response to methadone has been widely recognized. The purpose of this article is to review the literature on the pharmacogenetic factors underlying this variability. Materials & methods: This is a narrative overview of the literature on the genetic variants affecting pharmacodynamics and pharmacokinetics of methadone, retrieved from searches of databases such as PubMed and google scholar. Discussion: Clinical responses to methadone may be affected by genetic variants in the opioidergic, dopaminergic and neurotrophic pathways. Polymorphisms in genes related to disposition and elimination of methadone alter the pharmacokinetics, and possibly pharmacodynamics of methadone. Cytochrome P450 enzymes and P-glycoprotein variants contribute to the interindividual variability in methadone pharmacokinetics. Evidence for single gene variants affecting methadone response remains weak. Multiple genetic variants must be considered in conjunction to improve predictive ability. Conclusion: Evidence remains scarce at this time, to recommend pharmacogenetic testing before methadone administration. Well-powered clinical studies are needed with population pharmacokinetic-pharmacodynamic modeling and multigenetic signature-based predictions to enable tailored use of methadone in clinical practice.

Gestational buprenorphine exposure: Effects on pregnancy, development, neonatal opioid withdrawal syndrome, and behavior in a translational rodent model.

BACKGROUND: The opioid crisis has led to an increased number of pregnant opioid-dependent women receiving opioid-maintenance therapy (e.g. buprenorphine, BUP), but little is known about the consequences of gestational BUP exposure on pregnancy outcomes, maternal care, or offspring development. METHODS: Our translational rodent model began BUP exposure to adult female rats (N = 30) at least 7 days before conception and continued throughout the postpartum period. Both therapeutic low-dose (BUP-LD, 0.3 mg/kg, s.c.) and overexposure high-dose (BUP-HD, 1.0 mg/kg) doses of BUP were compared to saline control. Female rats were bred in house with drug-naïve adult male rats. The day after parturition, litters were culled to 5 males/5 females and assigned randomly to various behavioral tests and assessed either neonates or adolescents. Litter characteristics, maternal caregiving, Neonatal Opioid Withdrawal Syndrome (NOWS), offspring development and adolescent behaviors were evaluated. RESULTS: BUP-LD decreased maternal care, delayed offspring development, decreased offspring body weight, length, temperature, and pain sensitivity (p's < .05). BUP-HD drastically reduced maternal care and offspring survival, altered litter characteristics, and increased NOWS (p's < .05). CONCLUSION: These results demonstrate that the therapeutic BUP-LD in rats was relatively safe with subtle effects on maternal care and rodent offspring. However, overexposure BUP-HD in rats produced NOWS and compromised maternal caregiving as well as rodent offspring survival. More research is critical to validate the translational implication of these findings for human opioid-dependent mothers maintained on BUP-maintenance therapy.

The payer's role in addressing the opioid epidemic: It's more than money.

BACKGROUND AND OBJECTIVE: County, State, and Federal agencies are addressing the public health opioid crisis. Ohio's 51 county-based Alcohol, Drug Addiction and Mental Health Services (ADAMHS) Boards finance and regulate opioid treatment services within their jurisdictions. This three-year comparative trial collaborated with ADAMHS Boards (n = 14) to test the Advancing Recovery Framework, a suite of organizational and system change strategies designed to promote use of buprenorphine for opioid agonist therapy. METHODS: A multi-level intervention directed payers and treatment agencies to leverage their roles in increasing the use of buprenorphine. Half of the boards partnered with local substance use disorder treatment providers using the partnership strategies recommended by the Advancing Recovery (AR) framework. The comparison boards did not use the partnership strategies. RESULTS AND CONCLUSION: A logistic regression analysis detected increases in the number of patients receiving buprenorphine in both conditions. Buprenorphine use, as a percentage of patients with an opioid use disorder diagnosis, was significantly greater among the boards using the Advancing Recovery strategies during the three-year experimental period (odds ratio (OR) 1.63, 95% CI, 1.50 to 1.76, p < .001) and a one-year maintenance period (OR 2.13, 95% CI, 1.85 to 2.46, p < .001). Boards in both groups provided similar levels of financial support to implement and maintain buprenorphine prescribing. Strategy differences between the study conditions existed in use of a committee that facilitated payer-provider partnering and the ADAMHS boards setting expectations for using buprenorphine. Payer-provider partnerships achieved greater improvements and maximized the effectiveness of funding in increasing access to buprenorphine.

Opioid use disorder in Germany: healthcare costs of patients in opioid maintenance treatment.

BACKGROUND: Opioid Use Disorder (OUD) is a substance use disorder with a chronic course associated with comorbid mental and somatic disorders, a high burden of psychosocial problems and opioid maintenance treatment (OMT) as a standard treatment. In the US, OUD imposes a significant economic burden on society, with annual societal costs estimated at over 55 billion dollars. Surprisingly, in Europe and especially in Germany, there is currently no detailed information on the healthcare costs of patients with OUD. The goal of the present research is to gather cost information about OUD patients in OMT with a focus on maintenance medication and relapses. METHODS: We analysed health claims data of four million persons covered by statutory health insurance in Germany, applying a cost-of-illness approach and aimed at examining the direct costs of OMT patients in Germany. Patients with an ICD-10 code F11.2 and at least one claim of an OMT medication were stratified into the treatment groups buprenorphine, methadone or levomethadone, based on the first prescription in each of the follow-up years. Costs were stratified for years with and without relapses. Group comparisons were performed with ANOVA. RESULTS: We analysed 3165 patient years, the total annual sickness funds costs were on average 7470 € per year and patient. Comparing costs of levomethadone (8400 €, SD: 11,080 €), methadone (7090 €, SD: 10,900 €) and buprenorphine (6670 €, SD: 7430 €) revealed significant lower costs of buprenorphine compared to levomethadone (p < 0.0001). In years with relapses, costs were higher than in years without relapses (8178 € vs 7409 €; SD: 11,622, resp. 10,378 €). In years with relapses, hospital costs were the major cost driver. CONCLUSIONS: The present study shows the costs of OUD patients in OMT for the first time with a German dataset. Healthcare costs for patients with an OUD in OMT are associated with more than two times the cost of an average German patients. Preventing relapses might have significant impact on costs. Patients in different OMT were dissimilar which may have affected the cost differences.

Breastfeeding in Women on Opioid Maintenance Therapy: A Review of Policy and Practice.

INTRODUCTION: Opioid use is epidemic in the United States. Opioid use disorder (OUD) in pregnancy, as well as neonatal abstinence syndrome, has quadrupled in the last decade, and opioid maintenance therapy is recommended for pregnant women with OUD. Breastfeeding is an important means of improving outcomes for these vulnerable women and newborns. The purpose of this study was to review current policy on breastfeeding and opioid maintenance therapy, the rates of breastfeeding among women in this population, and facilitators and barriers to implementing policy recommendations. METHODS: CINAHL, PubMed, the Cochrane Database of Systematic Reviews, Embase, and Web of Science were searched. Inclusion criteria included publication between 2013 and 2018, English language, human only, and original data (except for policy statements). Studies were excluded if they did not report original data and did not examine breastfeeding for women on opioid maintenance therapy. RESULTS: Eight policy statements and 17 original research studies were identified that met the search criteria. All the policy statements support breastfeeding for women who are stable on opioid maintenance therapy and do not have HIV. Despite this, rates of breastfeeding among women receiving opioid maintenance therapy remain low compared with women in the general population. Results of qualitative research indicates that women on opioid maintenance therapy face numerous barriers to breastfeeding, including misinformation from health care professionals. Quantitative research has only begun to identify interventions to improve breastfeeding outcomes in this population. Research was conducted primarily with white women receiving care at urban health care centers. DISCUSSION: Practice lags behind policy in terms of supporting breastfeeding in women receiving opioid maintenance therapy. There is a need for more research that includes African American and rural women on opioid maintenance therapy, as well as quantitative research that uses findings from qualitative research to identify the best possible interventions for improving breastfeeding outcomes for women on opioid maintenance therapy and their newborns. One significant need is for health care provider education regarding these policies as well as best practices for providing breastfeeding education and support to this population.

Harm reduction drug policy in Israel: what has been accomplished and what still needs to be done?

The leading formal drug policy in Israel is the traditional approach of abstinence, probation, and punitive measures based on three main pillars: Enforcement, Treatment and Rehabilitation, and Prevention. However, under the treatment pillar, Israel has adopted a number of harm reduction services, focused mostly on people who use heroin and people who inject drugs. These include Methadone Maintenance Treatment, Buprenorphine Maintenance Treatment, and Needle and Syringe Exchange Programs. More specialized services are designated mostly for people who use drugs, who frequent the largest open drug scene in Tel-Aviv. These include a health clinic, an emergency apartment for female addict sex-workers, and a 'First Step' center. Even so, the harm reduction approach has remained controversial, stigmatized, and is considered a sub-category for total-abstinence treatment in Israel. This paper follows the evolution of harm reduction interventions in Israel among people who use drugs and sheds light on the lack of a comprehensive, well-planned, formal national harm reduction drug policy. Additionally, this article expresses concern over the uncertain future of Israel's comprehensive and balanced drug treatment policies caused by the structural changes in abolishing the Israel Anti-Drug Authority, the statutory authority and central body in Israel that promoted and coordinated all national policies related to treatment and harm reduction. CONCLUSIONS: Although it is a major challenge to translate worldwide evidence and research findings into action and social change, recommendations are offered to implement a comprehensive harm reduction drug policy led by a multidisciplinary group of policy-makers across all areas of drug policy. These focus on expanding and developing more services for Opioid Maintenance Therapy patients and people who inject drugs as well as a national effort to reduce high levels of stigma and discrimination against them, encompassing other common substances and focusing on populations such as adolescents and young adults that engage in other types of substance use such as cannabis, amphetamine-type stimulants, and hallucinogens.

Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.

INTRODUCTION: Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.