Intrauterine exposure to maternal opioid maintenance treatment and associated risk factors may impair child growth.

AIM: How maternal opioid maintenance treatment (OMT) affects children is under-researched. This population-based registry study investigated child growth and somatic health following intrauterine exposure to this treatment. METHODS: Children born between 1 March 2011 and 30 May 2021 to mothers who used buprenorphine, buprenorphine-naloxone, or methadone throughout their pregnancies were followed for 2 years at the Helsinki University Hospital, Finland. Appropriate statistical tests were used to compare the treatment groups. RESULTS: Of the 67 neonates, 52% were male, 96% were born full-term and 63% were treated for neonatal opioid withdrawal syndrome. Otherwise, the children were predominantly healthy, although relatively small: 22% were small for gestational age, the methadone group children being the smallest. Foetal exposure to maternal methadone treatment, illicit drugs, hepatitis C and smoking were associated with small for gestational age; the former two were also associated with later slower growth, especially head growth and weight gain (p < 0.001). However, 29% were overweight at 2 years. CONCLUSION: Using child growth as the outcome, we found that buprenorphine-naloxone and buprenorphine-monotherapy had equal effects as forms of maternal OMT. Exposure to multiple risk factors may harm foetal and subsequent growth. We recommend long-term follow-up of children exposed to maternal OMT.

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.

A retrospective, observational study on medication for opioid use disorder during pregnancy and risk for neonatal abstinence syndrome.

OBJECTIVES: The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications-methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS). METHODS: In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine. RESULTS: Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant. CONCLUSIONS: Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS.

Medications for opioid use disorder (MOUD), such as buprenorphine and methadone, are effective in reducing the significant harms associated with untreated opioid use disorder (OUD) in nonpregnant and pregnant adults. While previous research clearly documents that the risks of MOUD in pregnancy are less than the risks of untreated OUD in pregnancy, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of methadone and buprenorphine. In a clinical sample of infants born to women with OUD, we showed that buprenorphine-exposed infants were at significantly reduced risk for neonatal abstinence syndrome compared with methadone-exposed infants. Our study adds to the growing body of evidence supporting the use of buprenorphine over methadone for the treatment of OUD among pregnant women.

Polyvinylpyrrolidone deposition disease in patients with intravenous opioid use: a case series.

The polymer polyvinylpyrrolidone (PVP) is an excipient widely used in prescription drugs. Depending on the molecular weight (MW), parenterally administered PVP may accumulate in various tissues. Consequently, moderate and high MW PVP have only been used in oral preparations since the late 1970s. Surprisingly, starting in 2009, pathology departments in Norway received biopsies revealing PVP deposition, all from patients with a history of intravenous drug use. We identified 13 patients with PVP deposition and re-evaluated 31 biopsies and two autopsies. Common indications for biopsy were renal insufficiency, anemia, pathological fractures, and abdominal complaints. We observed PVP deposits in all biopsies (kidney, hematopoietic bone marrow, bone, gastrointestinal tract, lymph node, and skin) and all sampled tissue from the autopsies. Overall, the clinical findings could be related to PVP deposits in the biopsies. In the most seriously affected patients, PVP deposition caused severe organ dysfunction and contributed to the fatal outcomes of two patients. All patients except for one were prescribed opioid substitution drugs (OSDs), and most of the patients admitted to having injected such medications. Several OSDs contain PVP. One methadone formulation that was marketed in Norway from 2007 to 2014 contained large amounts of very high MW PVP, making it the most likely source of PVP deposition. Although the presumed source of PVP in these patients has now been withdrawn from the market, pathologists should be aware of PVP deposits when evaluating biopsies from this patient group.

Treatments of Sexual Dysfunction in Opioid Substitution Therapy Patients: A Systematic Review and Meta-Analysis.

Sexual dysfunction is a common condition in the opioid substitution therapy (OST) population. We aimed to determine the efficacy and safety of treatment for sexual dysfunction in the OST population. We searched for interventional studies from Medline, PubMed, and Scopus. Three independent authors conducted a risk-of-bias assessment (RoB 2). A total of seven studies (five randomized-controlled trials, two quasi-experimental), including 473 patients with sexual dysfunction, were identified. Among these, three bupropion (n=207), one trazodone (n=75), two rosa Damascena (n=100), and one ginseng (n=91) studies had reported significantly improve various sexual functioning domains in both genders. In a meta-analysis, bupropion significantly increased male sexual function with standardized mean difference of 0.53; 95% confidence interval of 0.19-0.88; P < 0.01; I2=0. The adverse effects were minor for all agents, and no significant difference between treatment and placebo groups in randomized-controlled trials. These agents have a promising future as therapy for sexual dysfunction in the OST population. However, given the limited sample size and number of studies, further studies should be conducted to confirm the use of these agents.

Cognitive Outcomes of Young Children After Prenatal Exposure to Medications for Opioid Use Disorder: A Systematic Review and Meta-analysis.

Importance: The number of children with prenatal opioid exposure to medication for addiction treatment (MAT) with methadone and buprenorphine for maternal opioid use disorder is increasing, but the associations of this exposure with cognitive outcomes are not well understood. Objective: To examine the strength and consistency of findings in the medical literature regarding the association of prenatal exposure to MAT with early childhood cognitive development, particularly when accounting for variables outside MAT exposure. Data Sources: A search strategy obtained publications from PubMed, CINAHL, PsycINFO, Web of Science, and Embase from January 1972 to June 2019. Reference lists from identified articles were searched. Study Selection: Inclusion criteria were cohort studies, studies including children aged 1 to 60 months with at least 2 months of prenatal MAT exposure, studies using standardized direct-observation testing scales, and studies reporting means and SDs. Case reports, case series, historical controls, and reviews were excluded. Data Extraction and Synthesis: Two authors independently selected studies for inclusion, extracted data, and assessed study quality. Data extracted included demographic characteristics, covariates, sources of bias, and effect estimates. Meta-analysis was performed using random-effects models. This study was conducted according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Data extraction and synthesis were conducted between January 2018 and August 2019. Main Outcomes and Measures: Cognitive test scores and demographic variability between exposed and unexposed groups. Results: A total of 16 unique cohorts, described in 27 articles and including 1086 children (485 [44.7%] with MAT exposure), were included in a quantitative synthesis. On meta-analysis, MAT exposure was associated with lower cognitive development scores (pooled standardized mean difference, -0.57; 95% CI, -0.93 to -0.21; I2 = 81%). Multiple subanalyses on demographic characteristics (ie, maternal education, race/ethnicity, socioeconomic status, prenatal tobacco exposure, infant sex) were conducted. In the subanalysis of studies with comparable prenatal exposure to tobacco smoke, the association of MAT exposure with cognitive scores was no longer statistically significant and became homogeneous (standardized mean difference, -0.11; 95% CI, -0.42 to 0.20; I2 = 0%). Conclusions and Relevance: In this study, predefined subanalyses demonstrated how poor recruitment, particularly imbalances in maternal tobacco use, could contribute to a negative overall association of cognitive development test scores with prenatal MAT exposure. Promoting tobacco cessation for pregnant women with opioid use disorder should be prioritized in this high-risk population.

A Practical Approach for the Management of the Mixed Opioid Agonist-Antagonist Buprenorphine During Acute Pain and Surgery.

The use of buprenorphine, a mixed opioid agonist-antagonist, for the management of chronic pain and/or opioid use disorder is increasing. As such, medical providers will more frequently encounter patients on this therapy. In this paper, we synthesize existing knowledge (derived through keyword searches using MEDLINE databases) in a novel conceptual framework for patients on buprenorphine presenting with acute pain or for those requiring surgical or invasive procedures. This framework is based on three unique domains: the patient, the features of the acute pain insult, and the environment. We discuss important considerations regarding the unique aspects of buprenorphine formulations and dosing, and we describe the importance of multidisciplinary planning and multimodal analgesic strategies. We also highlight important differences in management strategies based upon the presence or absence of opioid use disorder. All medical providers must be prepared to guide the patient on buprenorphine safely through the acute care episode, which includes adequate treatment of acute pain and avoidance of iatrogenic harm, including both short-term complications (eg, respiratory depression) and long-term complications (eg, relapse to opioid use).

Factors Associated with Sleep Disorders among Methadone-Maintained Drug Users in Vietnam.

Sleep quality among heroin-dependent patients receiving methadone maintenance treatment (MMT) is not fully investigated in Vietnam. This study explored the prevalence of poor sleep quality in methadone-maintained patients and associated factors. This cross-sectional included 395 MMT patients at three clinics in Nam Dinh province, Vietnam. The Pittsburgh Sleep Quality Index (PSQI) was employed to measure patients' sleep quality. Sociodemographic, clinical, behavioral, psychological, and social support characteristics were collected. Multivariate Logistic and Generalized Linear Regression models were applied to identify associated factors. Among 395 patients, 26.6% had poor sleep quality according to the PSQI scale. People having jobs were less likely to have poor sleep quality and lower PSQI scores compared to unemployed patients. Those having spouses had lower PSQI scores than single patients. High depression, anxiety, and stress scores were associated with poor sleep quality and high PSQI scores. A longer duration of MMT increased the likelihood of experiencing poor sleep quality. Patients smoking tobacco daily or concurrently using drugs had lower PSQI scores than those that did not. This study highlights a moderate prevalence of poor sleep quality among Vietnamese MMT patients. Regular evaluation, appropriate psychological management, and social support, as well as the provision of employment opportunities, potentially improve the sleep quality of methadone-maintained patients.

Prevalence and correlates of suicide attempt among Chinese individuals receiving methadone maintenance treatment for heroin dependence.

To date, there have been very limited studies regarding the clinical epidemiology of attempted suicide in Chinese individuals with heroin-dependence. The objective of this study was to examine the prevalence and correlates of suicide attempt in Chinese individuals receiving methadone maintenance treatment for heroin dependence. Demographic, clinical, and psychosocial data of 603 methadone-maintained patients with heroin dependence were collected with a standardized self-administered questionnaire. The presence of suicide attempt and antisocial personality disorder was assessed by using a single question and the Mini-International Neuropsychiatric Interview 5.0. The one-month and lifetime prevalence rates of suicide attempt were 9.5% and 34.2%, respectively. In multivariable logistic regression, lifetime suicide attempt was significantly associated with female gender (OR = 2.81), being 20-39 years old (OR = 2.73), an education level of primary school or lower (OR = 2.07), poor economic status (OR = 3.06), injecting heroin before methadone maintenance treatment (OR = 2.92), depressive symptoms (OR = 3.46), anxiety symptoms (OR = 1.88), and antisocial personality disorder (OR = 2.85). Suicide attempt is very prevalent among Chinese individuals receiving methadone maintenance treatment for heroin dependence. Services for patients with heroin dependence in methadone maintenance treatment clinics in China should include psychosocial supports, periodic screening for suicide attempt and other suicidal behaviors and, when needed, psychiatric treatment and crisis intervention.

Magnetocardiographic identification of prolonged fetal corrected QT interval in women receiving treatment for opioid use disorder.

AIM: Pregnant women undergoing treatment for opioid use disorder (OUD) may be exposed to multiple QT prolonging agents. We used magnetocardiography to measure fetal QT intervals in mothers with OUD on buprenorphine therapy. METHODS: Fetal and maternal magnetocardiography was performed in pregnant women receiving buprenorphine-assisted treatment (Disorder group); these were matched by gestational age to pregnant women who were opiate naïve (Reference group). Corrected QT intervals were determined using Bazett's formula and compared between groups. RESULTS: A total of eight women in the Disorder group matched to eight in the Reference group. Seven of the mothers (88%) in the Disorder group were smokers; there were no smokers in the Reference group. The average fetal corrected QT was significantly longer (P = 0.022) in the Disorder group than that in the Reference group (505 milliseconds [ms] ± 68.6 [standard deviation] vs 383 ms ± 70.3 [standard deviation]). CONCLUSION: Novel data from this small sample demonstrate prolongation of fetal corrected QT in women with OUD participating in buprenorphine assisted therapy. Additional investigation from a larger sample is needed to clarify if fetal buprenorphine and/or tobacco exposure is associated with changes in fetal QT which would warrant further prenatal and postnatal testing.

Maternal buprenorphine treatment during pregnancy and maternal physiology.

BACKGROUND: Buprenorphine, used for opioid use disorder (OUD) treatment during pregnancy, provides unknown effects on maternal physiological activity. The primary aim of this report is to document acute effects of buprenorphine administration on indicators of maternal autonomic functioning. Effects of maternal buprenorphine dose and other substance exposures on maternal measures were examined, as were neonatal abstinence syndrome (NAS) outcomes. METHODS: Forty-nine pregnant, buprenorphine-maintained women yielded maternal physiologic information (heart rate and variability, electrodermal activity, and respiratory rate) at 24, 28, 32 and 36 weeks gestation. Monitoring at trough and peak maternal medication levels was implemented to ascertain acute physiologic effects of buprenorphine administration. RESULTS: Buprenorphine administration accelerated maternal heart rate and reduced variability at two gestational ages (24 and 36 weeks) and suppressed sympathetic (electrodermal) activation at 24, 28 and 32 weeks at times of peak maternal medication levels. Maternal autonomic parameters were unrelated to polysubstance exposure with the exception of cigarette smoking. Heavier smoking dampened maternal heart rate variability across gestation and potentiated reactivity to buprenorphine at 24 and 36 weeks. Heavier smoking was also associated with reduced electrodermal activity at 36 weeks. Buprenorphine dose was unrelated to observed effects. Larger degree of maternal heart rate reactivity to buprenorphine administration was related to more severe NAS expression. CONCLUSIONS: These findings detail the maternal autonomic response to buprenorphine administration but also illustrate the significant effect of concurrent cigarette use on maternal autonomic regulation. This suggests the importance of smoking-reduction strategies in the comprehensive, medication-assisted treatment of women with OUD.

QT length during methadone maintenance treatment: gene × dose interaction.

Methadone is known to be a risk factor for sudden death by enlarging ECG QT corrected (QTc) interval. For other medical conditions, QTc lengthening has been described as the result of interactions between pharmacological treatments and genetic factors. Former heroin-dependent subjects under methadone maintenance treatment in remission for at last 3 months were recruited. We studied the association between QTc length (Bazett formula) and 126 SNPs located on five genes (KCNE1, KCNQ1, KCNH2, NOS1AP and SCN5A) previously associated with drug-induced QT prolongation. Both SNP-based and gene-based approaches were used, and we tested also the interaction of the top SNP with methadone dosage to predict the QTc length. In our sample of 154 patients, current methadone daily dose was associated with QTc length (rPearson  = 0.26; P = 10-3 ). Only one SNP, rs11911509 on KCNE1, remained significantly associated with QT length after correction for multiple testing (P = 3.84 × 10-4 ; pcorrected  = 0.049). Using a gene-based approach, KCNE1 was also significantly associated with QTc length (pempirical  = 0.02). We found a significant interaction between methadone dosage and rs11911509 minor allele count (allele A vs. C; P = 0.01). Stratified analysis revealed that the correlation between QTc length and methadone dosage was restricted only to AA carriers of this top SNP. Patients' genetic background should be taken into account in the case of clinically relevant QT enlargement during methadone maintenance treatment.

Maternal and neonatal characteristics of a Canadian urban cohort receiving treatment for opioid use disorder during pregnancy.

The epidemic of prescription and non-prescription opioid misuse is of particular importance in pregnancy. The Society of Obstetricians and Gynaecologists of Canada currently recommends opioid replacement therapy with methadone or buprenorphine for opioid-dependent women during pregnancy. This vulnerable segment of the population has been shown to be at increased risk of blood-borne infectious diseases, nutritional insecurity and stress. The objective of this study was to describe an urban cohort of pregnant women on opioid replacement therapy and to evaluate potential effects on the fetus. A retrospective chart review of all women on opioid replacement therapy and their infants who delivered at The Ottawa Hospital General and Civic campuses between January 1, 2013 and March 24, 2017 was conducted. Data were collected on maternal characteristics, pregnancy outcomes, neonatal outcomes and corresponding placental pathology. Maternal comorbidities identified included high rates of infection, tobacco use and illicit substance use, as well as increased rates of placental abruption compared with national averages. Compared with national baseline averages, the mean neonatal birth weight was low, and the incidence of small for gestational age infants and congenital anomalies was high. The incidence of NAS was comparable with estimates from other studies of similar cohorts. Findings support existing literature that calls for a comprehensive interdisciplinary risk reduction approach including dietary, social, domestic, psychological and other supports to care for opioid-dependent women in pregnancy.

Antagonist treatment is just as effective as replacement therapy for opioid addiction but neither is used often enough.

One of the most malignant illnesses in psychiatry is opioid addiction. This disorder has resulted in a current epidemic of addiction, overdose, and death that continues in large part because of the lack of robust treatments and the surprising lack of utilization of the treatments that are available.

Sexual Desire in Opiate-Dependent Men Receiving Methadone-Assisted Treatment.

Low sexual desire (SD) is not life threatening, but its negative impact on the quality of life and intimacy of a relationship among the patients on methadone maintenance therapy (MMT) is significant. This cross-sectional study involved 183 men on MMT who were interviewed and who completed the Malay version of the SDI-2 (SDI-2-BM), the Malay version of the self-rated Montgomery-Asberg Depression Rating Scale (MADRS-BM) and World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) questionnaires. Findings showed 32.8% ( n = 60) participants had low SD. Those who were older, had sexual partners, and were smokers achieved lower scores in both dyadic SD (≤24) and solitary SD (≤6), and suffered lower quality of life in their social relationship. MMT is very cost-effective in rehabilitating opioid dependence; however, as clinicians, we need to address and manage the issues of low SD and depression among patients on MMT, especially the older men.

Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence, characteristics, and related factors.

BACKGROUND: Observational studies have reported a high prevalence of obesity and diabetes in subjects on methadone therapy; there are, however, limited data about metabolic syndrome. The aim of the study was to evaluate the prevalence of metabolic syndrome and related factors in individuals with heroin use disorder on methadone therapy. METHODS: A cross-sectional study in individuals with heroin use disorder on methadone therapy at a drug abuse outpatient center. Medical examinations and laboratory analyses after a 12-hour overnight fast were recorded. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. RESULTS: One hundred and twenty-two subjects were included, with a mean age of 46.1 ± 9 years, a median body mass index (BMI) of 25.3 kg/m2 (interquartile range [IQR]: 21.2-28), and 77.9% were men. Median exposure to methadone therapy was 13 years (IQR: 5-20). Overweight and obesity were present in 29.5% and 17.2% of the participants, respectively. Metabolic syndrome components were low high-density lipoprotein (HDL) cholesterol (51.6%), hypertriglyceridemia (36.8%), high blood pressure (36.8%), abdominal obesity (27.0%), and raised blood glucose levels (18.0%). Abdominal obesity was more prevalent in women (52% vs. 20%, P = >0.01) and high blood pressure more prevalent in men (41.1% vs. 22.2%, P = .07). Prevalence of metabolic syndrome was 29.5% (95% confidence interval [CI]: 16.6-31.8). In the multivariate logistic regression analysis, BMI (per 1 kg/m2 increase odds ratio [OR]: 1.49, 95% CI: 1.27-1.76) and exposure time to methadone therapy (per 5 years of treatment increase OR: 1.38, 95% CI: 1.28-1.48) were associated with metabolic syndrome. CONCLUSIONS: Overweight and metabolic syndrome are prevalent findings in individuals with heroin use disorder on methadone therapy. Of specific concern is the association of methadone exposure with metabolic syndrome. Preventive measures and clinical routine screening should be recommended to prevent metabolic syndrome in subjects on methadone therapy.

Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

OBJECTIVE: Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS. STUDY DESIGN: This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded. RESULTS: Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001). CONCLUSION: Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.

Rosa Damascena oil improved methadone-related sexual dysfunction in females with opioid use disorder under methadone maintenance therapy - results from a double-blind, randomized, and placebo-controlled trial.

BACKGROUND: Methadone maintenance therapy (MMT) is provided to patients with opioid use disorder (OUD). However, as with all opioids, methadone impacts negatively on sexual function. To counter this, Rosa Damascena oil (RDO) has been used successfully for opioid-dependent male patients under MMT and with methadone-related sexual dysfunction (MRSD). In the present study, we tested the possible influence of RDO on sexual function and sex hormones of opioid-dependent female patients undergoing MMT and with MRSD. METHODS: Fifty female patients (mean age: 38.8 years) diagnosed with OUD, undergoing MMT and with MRSD were randomly assigned either to the RDO or the placebo condition. At baseline, patients completed questionnaires covering socio-demographic and OUD-related information. At baseline, and four and eight weeks later they additionally completed questionnaires on sexual function and happiness. Blood samples to assess thyroid hormones, prolactin, progesterone, and estradiol levels were taken at baseline and eight weeks later (end of the study). RESULTS: Over time sexual function and happiness increased, but more so in the RDO condition than in the placebo condition. Over time, prolactin decreased, and progesterone, and estradiol increased, but again more so in the RDO condition. Sex hormone levels and sexual function were statistically unrelated. CONCLUSIONS: Results from this double-blind, randomized, and placebo-controlled clinical trial showed that opioid-dependent females undergoing MMT and with MRDS did benefit from RDO administration, as sexual function and happiness increased, and female sexual hormone levels changed in positive directions.

Increased DNA Methylation of ABCB1, CYP2D6, and OPRM1 Genes in Newborn Infants of Methadone-Maintained Opioid-Dependent Mothers.

OBJECTIVE: To investigate whether in utero opioid exposure, which has been linked to adverse neurodevelopmental and social outcomes, is associated with altered DNA methylation of opioid-related genes at birth. STUDY DESIGN: Observational cohort study of 21 healthy methadone-maintained opioid-dependent mother-infant dyads consecutively delivered at >36 weeks of gestation, and 2 comparator groups: smoking, "deprived" opioid-naïve mother-infant dyads (n = 17) and nonsmoking, "affluent" opioid-naïve mother-infant dyads (n = 15). DNA methylation of ABCB1, CYP2D6, and OPRM1 genes for mothers and babies was determined from buccal swabs. Plasma methadone concentrations were additionally measured for methadone-maintained opioid-dependent mothers. RESULTS: DNA methylation for ABCB1 and CYP2D6 was similar in opioid-naïve infants compared with their mothers, but was less for OPRM1 (3 ± 1.6% vs 8 ± 1%, P < .0005). Opioid-exposed newborns had similar DNA methylation to their mothers for all genes studied and greater methylation of ABCB1 (18 ± 4.8% vs 3 ± 0.5%), CYP2D6 (92 ± 1.2% vs 89 ± 2.4%), and OPRM1 (8 ± 0.3% vs 3 ± 1.6%) compared with opioid-naïve newborns (P < .0005 for all 3 genes). Infant DNA methylation was not related to birth weight, length of hospital stay, maternal smoking, dose or plasma concentration of methadone at delivery, or postcode of residence. CONCLUSIONS: In utero exposure to opioids is associated with increased methylation of opioid-related genes in the newborn infant. It is not clear whether these findings are due to opioid exposure per se or other associated lifestyle factors.

Ischemic Hand Complications From Intra-Arterial Injection of Sublingual Buprenorphine/Naloxone Among Patients With Opioid Dependency.

BACKGROUND: Sublingual buprenorphine/naloxone, a common treatment for opioid dependence, is frequently abused by intravenous injection. Inadvertent intra-arterial injection of buprenorphine/naloxone can produce acute ischemic insult to the hand due to gelatin embolism. Our purpose was to review a series of these patients in order to describe the clinical entity, review the outcomes, and propose a rational treatment algorithm. METHODS: Clinical records of all patients evaluated by the hand surgery team between 2011 and 2015 for ischemia of the hand after buprenorphine/naloxone injection were reviewed. Treatment, complications, and amount of tissue loss were recorded. Patients presenting within 48 hours of the injection were treated with intravenous heparin for 5 days, followed by oral aspirin and clopidogrel for 30 days. Those presenting after 48 hours were treated with aspirin and clopidogrel only. RESULTS: Ten patients presented during the review period. Average follow-up time was 13 weeks. Eight had ischemia of the radial side of the hand, 1 of the ulnar side, and 1 had bilateral ischemia. Three patients were treated with intravenous heparin and 5 with oral agents. Two presented with dry gangrene and did not receive anticoagulation. All patients experienced tissue loss. There was no difference in outcome regardless of treatment. CONCLUSIONS: With the increasing use of sublingual buprenorphine/naloxone in opioid dependency, ischemic hand injuries will be seen with greater frequency. Whereas outcomes did not vary with treatment modality in this series, further study is needed to determine the most effective treatment of these injuries.