Dose-dependent naloxone-induced morphine withdrawal symptoms in opioid-dependent males-a double-blinded, randomized study.

AIMS: Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation. METHODS: In a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine-naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine-naloxone 200:1]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated. RESULTS: Intravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone. CONCLUSION: Morphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.

Comorbidity Patterns Among Patients With Opioid Use Disorder and Problem Gambling: ADHD Status Predicts Class Membership.

Objective: Psychiatric comorbidities are highly prevalent among individuals affected by substance use disorders and those with non-substance-related addictive disorders such as gambling disorder. More recently, the frequent co-occurrence of substance use disorders and attention-deficit hyperactivity disorder (ADHD) has received particular attention. The aim of our study was to identify patterns of psychiatric comorbidity and to examine associations between patient group and ADHD status with class membership. Methods: Participants were patients with opioid use disorder enrolled in opioid maintenance treatment (OMT), either recruited from the community (n = 142; M age = 35.8 years; 38.7% female) or prison (n = 133; M age = 35.7 years; 21.8% female), and patients undergoing treatment for problem gambling (PrG; n = 80; M age = 43.1 years; 20% female). To enable direct comparisons, the following instruments were applied: Mini International Neuropsychiatric Interview, Adult ADHD self-report scale, Wender Utah Rating Scale, and European Addiction Severity Index. We used a latent class analysis (LCA) to identify psychiatric comorbidity patterns and a multinomial logistic regression to examine associations between patient group, ADHD status, age, and gender with class membership. Results: The LCA resulted in a three-class solution: (1) a class of individuals with a relatively low probability of current psychiatric comorbidities, except for a high probability of substance use disorders; (2) a class with markedly increased probabilities of current and recurrent psychiatric comorbidities, especially for major depression; and (3) a class with very low probabilities of psychiatric comorbidities, except for moderate probabilities of substance use disorders and antisocial personality disorder. Both OMT patients recruited from the community and those in prison were less likely than PrG patients to be assigned to the most burdened class with respect to psychiatric comorbidity (class 2). Further, both individuals with ADHD in childhood and those with adult ADHD were more likely members of class 2. Conclusions: PrG patients seem to be at an even higher risk for psychiatric comorbidities compared to OMT patients. Raising awareness among practitioners for the high prevalence of psychiatric comorbidities among patients with gambling disorder and individuals with ADHD is crucial to initiate adequate treatment and to improve response.

Attention-Deficit Hyperactivity Disorder Symptom Status in a Mixed Gender Population of Opioid-Maintained Prison Inmates.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) often coincides with substance abuse and delinquency. A sample of opioid-maintained inmates was assessed for symptoms of ADHD, substance abuse history, types of offense, psychiatric comorbidities, and psychopharmacological treatment using a standardized battery of instruments. METHOD: Adult inmates (n = 133, mean age 35.7 years, 21.8% female) in opioid-maintenance therapy (OMT) were administered the Adult ADHD self-report scale, Wender Utah Rating Scale, Mini International Neuropsychiatric Interview, -European Addiction Severity Index. RESULTS: Fifty percent screened positive for childhood and 17% for adult ADHD, four (3.1%) received ADHD medication. Inmates with ADHD symptom status were significantly younger at first substance abuse, reported more drug overdoses, longer duration of cocaine and prescribed medication abuse and more in- and outpatient treatments (all p < 0.05). For all inmates in OMT a high rate of psychiatric comorbidities was observed (78.9%). CONCLUSION: There is a need for assessment of ADHD and other psychiatric comorbidities in OMT prisoners. Evidence-based treatment should be routinely provided.

Adult ADHD Is Associated With Gambling Severity and Psychiatric Comorbidity Among Treatment-Seeking Problem Gamblers.

Objective: The aim of this study is as follows: (a) exploring retrospective childhood and adult ADHD symptomatology in treatment-seeking gamblers, (b) providing detailed characteristics of the association between pathological gambling (PG) and ADHD, and (c) identifying risk factors for a history of ADHD. Method: Eighty problem gamblers (20% female) were examined using a standardized interview (PG: Diagnostic and Statistical Manual of Mental Disorders [4th ed.; DSM-IV] criteria, Gambling Attitudes and Beliefs Survey; ADHD: Wender Utah Rating Scale-deutsche Kurzform, Adult ADHD Self-Report Scale; comorbidities: Mini International Neuropsychiatric Interview). Results: Forty-three percentage of patients screened positive for childhood ADHD, and in 11%, ADHD persisted in adulthood. Patients with adult ADHD had more severe gambling problems (p = .009, d = 1.03) and a higher number of psychiatric comorbidities (p < .001, d = 1.62) compared with those without ADHD. Substance abuse/dependence constituted a predictor for having a history of ADHD (odds ratio [OR] = 4.07, p = .025). Conclusion: ADHD-PG comorbidity is linked to factors that worsen the prognosis. Thus, screening for ADHD and verifying persistence in adulthood should be an integral component in the interdisciplinary treatment of problem/pathological gamblers.

Hepatitis C infection and psychiatric burden in two imprisoned cohorts: Young offenders and opioid-maintained prisoners.

Prisoners constitute a considerable gap in the hepatitis C virus (HCV) tested population. The present study examined HCV prevalence in imprisoned opioid-maintained patients (OMT-P) and adolescents and young adults (AYA, 14-26 years). In addition, HCV testing and treatment provision, knowledge of HCV status and psychiatric comorbidity were assessed. Data collection took place in six Austrian prisons. Participants were N = 133 for OMT-P (78% male, mean age 35.7 years) and N = 71 for AYA (100% male, mean age 19.8 years). Analysis of HCV serology was conducted. Psychiatric comorbidity and addiction severity were assessed applying standardized questionnaires and interviews. Antibodies were detected in 74.4% of OMT-P, and in 45.0% HCV infection was confirmed. Only one AYA was infected with HCV. None of the participants was receiving treatment for HCV. Eleven percent of OMT-P (50.7% of AYA) did not know their HCV status, and 14.3% of OMT-P (36.6% of AYA) had not been tested in prison. Among OMT-P, lifetime IDU [OR = 330.33, CI = 25.91-4433.20] and age at first IDU [OR = 0.90, CI = 0.82-0.98] significantly predicted HCV status. In both samples, a high prevalence of affective disorders was observed. Despite the high prevalence of HCV among opioid-dependent detainees, the unique opportunities for comprehensive testing and treatment of HCV are substantially underutilized. This is in stark contrast to the UN Basic Principles for the Treatment of Prisoners.

Telemedical Coaching Improves Long-Term Weight Loss in Overweight Persons: A Randomized Controlled Trial.

BACKGROUND: Lifestyle interventions have shown to be effective when continuous personal support was provided. However, there is lack of knowledge whether a telemedical-approach with personal coaching contributes to long-term weight losses in overweight employees. We, therefore, tested the hypothesis that telemedical-based lifestyle interventions accompanied with telemedical coaching lead to larger weight losses in overweight persons in an occupational health care setting. METHODS: Overweight employees (n=180) with a body mass index (BMI) of >27 kg/m2 were randomized into either a telemedical (TM) group (n=61), a telemedical coaching (TMC) group (n=58), or a control group (n=61). Both intervention groups were equipped with scales and pedometers automatically transferring the data into a personalized online portal, which could be monitored from participants and coaches. Participants of the TMC group received additionally one motivational care call per week by mental coaches to discuss the current data (current weight and steps) and achieving goals such as a healthy lifestyle or weight reduction. The control group remained in routine care. Clinical and anthropometric data were determined after the 12-week intervention. Additionally, weight change was followed up after 12 months. RESULTS: Participants of TMC (-3.1 ± 4.8 kg, p<0.0001) and TM group (-1.9 ± 4.0 kg; p=0.0012) significantly reduced weight and sustained it during the 1-year follow-up, while the control group showed no change. Compared to the control group only weight loss in the TMC group was significantly different (p<0.001) after 12 months. TMC and TM group also reduced BMI, waist circumference, and LDL cholesterol. Moreover, TMC group improved additionally systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, and HbA1c. CONCLUSIONS: Telemedical devices in combination with telemedical coaching lead to significant long-term weight reductions in overweight persons in an occupational health care setting. This study is registered with NCT01868763, ClinicalTrials.gov.

Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes.

BACKGROUND: Methadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent. METHODS: Participants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child's life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined. RESULTS: Tests of mean differences between children prenatally exposed to methadone vs. buprenorphine over the three-year period yielded 2/37 significant findings for children. Similarly, tests of mean differences between children treated for NAS relative to those not treated for NAS yielded 1/37 significant finding. Changes over time occurred for 27/37 child outcomes including expected child increases in weight, head and height, and overall gains in cognitive development, language abilities, sensory processing, and temperament. For mothers, significant changes over time in parenting stress (9/17 scales) suggested increasing difficulties with their children, notably seen in increasing parenting stress, but also an increasingly enriched home environment (4/7 scales) CONCLUSIONS: Findings strongly suggest no deleterious effects of buprenorphine relative to methadone or of treatment for NAS severity relative to not-treated for NAS on growth, cognitive development, language abilities, sensory processing, and temperament. Moreover, findings suggest that prenatal opioid agonist exposure is not deleterious to normal physical and mental development.

Correction to: Psychiatric comorbidity and intimate partner violence among women who inject drugs in Europe: a cross-sectional study.

The original version of this article unfortunately missed the Acknowledgment.

Psychiatric comorbidity and intimate partner violence among women who inject drugs in Europe: a cross-sectional study.

Women who inject drugs (WWID) are an especially vulnerable group of drug users. This study determined the prevalence of psychiatric comorbidity and intimate partrner violence (IPV), and factors associated with psychiatric comorbidity among WWID recruited from drug treatment services (67%) and harm reduction services in five European regions in Austria, Catalonia, Italy, Poland, and Scotland. Psychiatric comorbidity was assessed among 226 WWID using the Dual Diagnosis Screening Instrument. IPV was assessed using the Composite Abuse Scale and injecting and sexual risk behaviors were assessed using a battery of questionnaires adapted and developed for the study. Eighty-seven percent met criteria for at least one lifetime psychiatric disorder. The most common disorders were depression (76%), panic (54%), and post-traumatic stress (52%). WWID recruited in drug treatment services were almost three times as likely (OR 2.90 95% CI 1.30-6.43; p = 0.007) to meet criteria for a lifetime psychiatric disorder than those recruited from harm reduction services, specifically dysthymia (OR 5.32 95% CI 2.27-12.48; p = 0.000) and post-traumatic stress disorder (OR 1.83 95% CI 1.02-3.27; p = 0.040). WWID who reported sharing needles and syringes were almost three times as likely to meet criteria for lifetime psychiatric comorbidity than those who did not (OR 2.65 95% CI 1.07-6.56). Compared to WWID who had not experienced IPV, victims (70%) were almost two times more likely to meet criteria for post-traumatic stress disorder (OR 1.95 95% CI 1.10-3.48). Psychiatric comorbidity and IPV among WWID are common. Drug treatment and harm reduction services should address psychiatric comorbidity and IPV to improve treatment outcomes.

Monitoring neonatal abstinence syndrome in buprenorphine-exposed in vitro fertilization twins: A case study.

BACKGROUND: Prior studies have reported on the pregnancies and outcomes of in vitro fertilization (IVF) in special subpopulations; however, there is a lack of studies on opioid-exposed IVF-conceived neonates. CASE PRESENTATION: A young adult IVF-pregnant woman was maintained on buprenorphine throughout pregnancy and received follow-up from the addiction clinic from estimated gestational week 32. She delivered healthy dichorionic twins via cesarean section at 38 weeks gestational age (buprenorphine dose at time of delivery: 16 mg). All maternal supervised urinalysis taken as of gestational week 32 were negative for concomitant substances (prior to treatment initiation at the addiction clinic, only self-reports of abstinence from concomitant substances were available). Both healthy children (male birth weight: 3140 g, female birth weight: 2650 g) developed an unusual course of neonatal abstinence syndrome (NAS) requiring extensive treatment (total morphine dose male: 22 mg, and female: 26.75 mg; length of treatment: 33 and 34 days, respectively; duration of hospitalization: 40 days). DISCUSSION: The highly severe and long-lasting NAS in both neonates represents a very unusual course following an uneventful pregnancy, and influencing iatrogenic factors cannot be ruled out. Given the multiple variables influencing infant outcomes, this highlights the importance of high-quality, evidence-based standard operating procedures, which (1) are initiated as early as possible during pregnancy to minimize risk factors for adverse infant outcomes, such as concomitant substance use during pregnancy; (2) support the substance-dependent woman throughout the postpartum period, especially in cases of multiple and/or IVF-conceived pregnancies, where additional challenges may arise; and (3) consider the right of everyone to the enjoyment of the highest attainable standard of physical and mental health.

Opioid Maintenance Treatment--A Call for a Joint European Quality Care Approach.

AIMS: The aim of this exploratory analysis of European Quality Audit of Opioid Treatment data was to identify areas of improvement for current opioid maintenance treatment (OMT) approaches. METHODS: Factors facilitating treatment entry, retention and refusal were compared between 8 European countries and between OMT patient (OMT-P) and active opioid user (AOU) sample groups. Both groups were divided into those who had never had OMT before (un-experienced OMT-P (n = 573) and AOU (n = 360)) and those who had been maintained at least once prior to this investigation (experienced OMT-P (n = 746) and AOU (n = 377)). RESULTS: The European comparison showed that motives for starting OMT vary distinctly between countries (p ≤ 0.001). Transnationally, experienced AOU reported concerns about their ability to follow treatment rules and negative treatment experiences as decisive reasons for staying out of OMT. Greater flexibility, less pressure to reduce their treatment dose and greater treatment structure were ranked significantly higher by experienced compared to un-experienced OMT-P as factors that might facilitate treatment retention (p ≤ 0.05). CONCLUSION: Increasing awareness of potential shortcomings of OMT delivery systems is crucial to optimally match treatment approaches to patient needs and also to reduce the considerable economic burden of addiction to society.

Tobacco Cessation: A Guide for Clinicians.

Smoking behavior is a complex phenomenon that entails innumerable variables. Successful treatment interventions must be based on a comprehensive diagnosis and must consider the whole spectrum of factors influencing smoking behavior and nicotine dependence.

Characteristics and quality of life of opioid-dependent pregnant women in Austria.

This study investigated pregnant opioid-dependent women undergoing maintenance therapy, applying a multidisciplinary, case-management approach at the Addiction Clinic of the Medical University of Vienna, Austria. It aimed at characterizing the patients' basic demographic and clinical parameters and evaluating their overall quality of life (QoL) prepartum and postpartum. Three hundred ninety women were treated between 1994 and 2009 with buprenorphine (n = 77), methadone (n = 184), or slow-release oral morphine (SROM) (n = 129) on an outpatient basis throughout their pregnancy and postpartum period. All patients were subject to standardized prepartum and postpartum medical and psychiatric assessments, including QoL assessments using a German adaptation of the Lancashire QoL Profile (Berliner Lebensqualitaetsprofil), and regular supervised urine toxicologies. No medication group differences were revealed regarding basic demographic or clinical data. Mean maintenance doses (SD) at time of delivery were as follows: 64 mg (36 mg) methadone, 10 mg (6 mg) buprenorphine, 455 mg (207 mg) SROM. However, buprenorphine-medicated women showed significantly less concomitant benzodiazepine consumption than methadone- or SROM-maintained women (p = 0.005), and significantly less concomitant opioid consumption than methadone-maintained women (p = 0.033) during the last trimester. Overall QoL was good prepartum and postpartum in all measured domains except "finances" and "prospect of staying in the same housing situation," and no differences were observed in QoL among the three medication groups (p = 0.177). QoL improved significantly after delivery in most of the domains (p < 0.001). Although opioid-dependent pregnant women face high-risk pregnancies and show variability in addiction severity, they report good QoL independent of the medication administered. These results show that individually tailored treatment interventions are effective for this patient population and suggest a QoL improvement after delivery.

Substance abuse/dependence treatment: a European perspective.

During the past decade, substantial progress has been made in the field of addiction medicine in Europe, particularly regarding the development of new treatment interventions, resulting in a wide range of therapeutic options for patients with substance use disorders. However, not all interventions are evidence based. Patients with cannabis and cocaine/amphetamine use disorders and special patient populations especially lack evidence-based treatment recommendations. Many patients undergo treatment that has not been scientifically evaluated for quality and efficacy. Moreover, there are large disparities regarding availability and treatment access across Europe, with the new member states of the European Union (EU) reporting long waiting lists and low treatment coverage. Even in Austria, which ranks among the countries with relatively high treatment coverage and good diversification of treatment in opioid maintenance therapy due to the availability of methadone, buprenorphine, and slow-release oral morphine (SROM), a considerable population of untreated or inadequately treated patients exists. Treatment for substance use disorders in Europe still has scope for improvement in terms of treatment availability and access, which is ideally provided by further development and implementation of evidence-based interventions.

A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes.

Given that buprenorphine + naloxone is prescribed for opioid-dependent pregnant women, it is important to examine the extent to which it differs from buprenorphine alone, methadone, or methadone-assisted withdrawal on neonatal and maternal outcomes. Summary statistics on maternal and neonatal outcomes were collected from 7 previously published studies examining treatment for opioid-dependent pregnant women that represented a range of research methodologies. Outcomes from these studies were compared to the same outcomes for 10 women treated with the combined buprenorphine + naloxone product. There were no significant differences in maternal outcomes for buprenorphine + naloxone compared to buprenorphine, methadone, or methadone-assisted withdrawal. Preliminary findings suggest no significant adverse maternal or neonatal outcomes related to the use of buprenorphine + naloxone for the treatment of opioid dependence during pregnancy. However, further research should examine possible differences between buprenorphine + naloxone and buprenorphine alone or methadone in fetal physical development.

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.

Lessons learned from a comparison of evidence-based research in pregnant opioid-dependent women.

OBJECTIVES: Lessons learned in research and treatment of opioid dependence demonstrate the need to include pregnant women in clinical trials. METHODS: Two double-blind, double-dummy, randomized controlled trials (Pilot study, European sample(†) of MOTHER-trial) comparing buprenorphine and methadone in opioid-dependent pregnant women were conducted. In both studies, participants received voucher-based incentives for attendance and completion of study assessments. In the MOTHER trial, participants additionally received escalating voucher incentives for drug-free urine samples. Neonatal abstinence syndrome was treated with oral morphine solution based on standardized modified Finnegan scores. RESULTS: After a mean treatment period of 13.79 weeks in the Pilot study (PS, n = 18) and 20.78 weeks in the MOTHER-trial (MT, n = 41), respectively (p < 0.001), PS patients delivered at mean doses of 14.00 mg buprenorphine/52.50 mg methadone and MT participants at 13.44 mg buprenorphine/63.68 mg methadone. Nonsignificant differences regarding dropout rates were found (22% in PS versus 10% in MT), but dropout was significantly earlier in the MT (p = 0.013). Significantly higher rates of concomitant consumption of opioids and benzodiazepines occurred in the PS compared with the MT (p < 0.001), however, with no significant differences in neonatal data between both settings. CONCLUSIONS: Early treatment enrolment combined with contingency management contributes to reduced illicit drug use throughout pregnancy, surprisingly without influencing neonatal outcome parameters.

Should pregnant women with substance use disorders be managed differently?

Pregnant women with substance use disorders have multiple special needs, which might be best managed within a multiprofessional treatment setting involving medical, psychological and social care. Adequate treatment provision remains a challenge for healthcare professionals, who should undergo special training and education when working with this patient population. Careful assessment and screening is necessary to tailor interventions individually to the woman's needs in order to achieve beneficial clinical outcomes for mothers and newborns, whereas the choice of treatment options highly depends on the type of substance of abuse and evidence-based treatment interventions available. Economic considerations have shown that early multiprofessional treatment might yield better clinical outcomes and save healthcare costs over the lifespan.