Harald Eder

Buprenorphine Maintenance in Pregnant Opiate Addicts

Opioid maintenance agents such as methadone and slow-release morphine have provided beneficial effects in pregnant opioid-dependent women in both themselves and their child. However, one of the major drawbacks involved with these agents is that they cause an increase in the severity of neonatal abstinence syndrome (NAS) when compared to mothers using heroin. Consequently, a trial was performed to investigate the effects of buprenorphine use during pregnancy. A total of nine pregnant opioid-dependent women were transferred from either a mean daily dose of 39.7 mg methadone or 400 mg slow-release morphine to a mean daily dose of 8.1 mg buprenorphine. The buprenorphine-maintained patients were integrated into an already established outpatient maintenance treatment programme covering all aspects of prenatal and perinatal care. Results demonstrated that buprenorphine administration in opioid-dependent pregnant patients is efficacious and well tolerated. Babies born to buprenorphine-maintained patients had birthweight and Apgar scores within the normal range (2,500–4,500 g and 9–10, respectively) and no evidence of opioid-related NAS was observed. The results from this preliminary study indicate the potential for buprenorphine maintenance therapy in pregnant addicts, although further research is required to confirm this hypothesis.

Maintenance therapy with synthetic opioids and driving aptitude.

Aims: To assess the influence of methadone and buprenorphine maintenance treatment on the driving aptitude of opioid-dependent patients. Design: Prospective, open label, outpatient maintenance, single-blind (investigator) study. Participants and Setting: Thirty opioid-dependent patients maintained on either methadone or buprenorphine were recruited from the drug-addiction outpatient clinic in Vienna. Measurements: The traffic-relevant performance dimensions of the participants were assessed 22 h after receiving synthetic opioid maintenance therapy, by a series of seven tests constituting the Act & React Test System (ART) 2020 Standard test battery, developed by the Austrian Road Safety Board (ARSB). To test for additional consumption of illicit substances, blood and urine samples were taken at the beginning of the tests. Findings: The patient group only differed from control subjects in two of the ART 2020 Standard tests. During a task to test the subject’s attention under monotonous circumstances (Q1 test), patients had a significantly greater number of reactions (p = 0.027) and a significantly higher percentage of incorrect reactions than control subjects. When driving in a dynamic environment (DR2 test) patients had a significantly longer mean decision time (p = 0.029) and mean reaction time (p = 0.009) compared with control subjects. Interestingly, when separated into treatment groups, the mean decision and reaction times of buprenorphine-maintained patients in the DR2 test did not differ from controls, whereas patients maintained on methadone showed significantly prolonged mean decision (p = 0.009) and reaction times (p = 0.004). In this same test, patients who had consumed additional illicit drugs had a longer mean reaction time compared with control subjects (p = 0.036). Conclusion: The synthetic opioid-maintained subjects investigated in the current study did not differ significantly in comparison to healthy controls in the majority of the ART 2020 Standard tests.

Comparison of Buprenorphine and Methadone Maintenance in Opiate Addicts

As a maintenance agent for opioid dependency, buprenorphine offers advantages such as a lower level of dependence and minimal withdrawal symptoms, due to its partial agonist properties at the µ-opioid receptor. Previous studies have shown 8 mg sublingual buprenorphine to be equivalent to 60 mg oral methadone in terms of retention rate and opioid-negative urine levels. In a 24-week, ongoing European study, 34 opioid-dependent subjects were assessed; 16 receiving buprenorphine and 18 methadone. A free dosing schedule was used with no upper limit for methadone dosing but with a maximum buprenorphine dose of 8 mg. Screening prior to the study excluded subjects with polysubstance dependence, somatic disease and/or HIV infection. Primary outcome measures were abstinence from other drugs, for which subjects provided weekly urine samples for analysis of opioids, cocaine and benzodiazepines, and retention in treatment. Patients in the buprenorphine group provided a greater proportion of negative urine samples, in particular cocaine-negative samples, compared with the methadone group, although this was not statistically significant. Retention in the buprenorphine group was significantly lower than in the methadone group, suggesting that the 8 mg buprenorphine limit may have biased the results in favour of methadone, and that this dose may have been too low for those subjects with high levels of dependence. However, buprenorphine is clearly effective in the more motivated subjects and further investigation in this subgroup is recommended.

Use of Slow-Release Oral Morphine for the Treatment of Opioid Dependence

Aims: In addition to methadone, other synthetic opioids are now available for the treatment of opioid dependence. The study investigated the treatment satisfaction of oral slow-release morphine for maintenance therapy in opioid-dependent patients in an open-label 3-week study. Design: We evaluated the treatment satisfaction of oral slow-release morphine hydrochloride for 3 weeks in 110 patients meeting the diagnosis of opioid dependence (DSM-IV 304.0) or polysubstance dependence (DSM-IV 304.9). Measurements: Primary outcome measures were the study retention rate, urinalysis for additional illicit consumption other than heroin, cravings and withdrawal symptoms 24 h after the last intake of the medication (duration of action of treatment). Findings: In total, 103 patients completed the study, representing a retention rate of 94%. Patients reported significant improvements in somatic complaints, as well as significant reductions in heroin and cocaine cravings (p < 0.0001) and in additional consumption of cocaine in supervised urinalysis (p = 0.0083). Additional illicit consumption of benzodiazepines remained unchanged. Conclusions: The high study retention rate implies a good acceptance of slow-release acting oral morphine. However, randomised, double-blind, double-dummy studies with a longer investigational period are needed to meet criteria for evidence-based medicine.

Outpatient Opiate Detoxification Treatment with Buprenorphine

In an open study design, 50 opioid-dependent subjects (DSM-IV: 304.0) were investigated in a gradual detoxification treatment with buprenorphine. The study was performed at the drug addiction outpatient clinic of the Department of General Psychiatry at the University of Vienna. Subjects had to contact the outpatient clinic on a daily basis and buprenorphine was administered according to their clinical status. Withdrawal symptoms were evaluated by applying the WANG scale. Urine samples were screened for drug toxicology to exclude additional consumption. In this investigation buprenorphine was applied sublingually in a free dosage scheme aimed at completing detoxification treatment within 10 days by reducing buprenorphine on a daily basis. A mean daily dosage of 2.3 mg buprenorphine was required by patients on day 1 of the treatment period. The highest mean daily buprenorphine dosage was given on day 2, followed by a daily reduction over the study period. The result of this open study design revealed that a gradual daily reduction of buprenorphine might be a successful alternative outpatient detoxification treatment in opioid-dependent subjects. Compliance was 70%, the reported and evaluated withdrawal symptoms during the study period were moderate.

Pregnancy and substance abuse

Summary The fetal consequences of drug abuse during pregnancy remain underestimated. Obstetrical complications of cigarette smoking include growth retardation, spontaneous abortion and sudden infant death syndrome; alcohol abuse leads to nutritional deficiencies and fetal alcohol syndrome. Heroin and cocaine consumption result in medical, nutritional and social neglect; cocaine and amphetamine cause hypertension, abruptio placentae; all three drugs of abuse cause preterm labor, with neonates being small for gestational age. Intravenous abuse also increases the risk of contracting infectious disease. The recommended treatment standard is to maintain pregnant, opioid-dependent women on synthetic opioids such as methadone, but newer substances like slow-release morphine and buprenorphine may also be beneficial. Treatment should be interdisciplinary and consider the high prevalence of substance dependent partners. Programmes should be initiated to identify women at risk and provide early treatment to improve the outcome for mother and child. Care must be provided in a supportive, proactive and non-judgemental fashion.

Influence of peak and trough levels of opioid maintenance therapy on driving aptitude

To evaluate driving aptitude and traffic-relevant performance at peak and trough medication levels in opioid-dependent patients receiving maintenance therapy with either buprenorphine (mean: 13.4 mg) or methadone (52.7 mg) and a medication-free control group, the Addiction Clinic at Medical University Vienna conducted a prospective, open-label trial where 40 opioid-dependent patients maintained either on buprenorphine or methadone were assessed regarding their traffic-relevant performance. Using the standardized Act and React Testsystem (ART) 2020 Standard test battery, traffic-relevant performance was analysed 1.5 h (peak level) and 20 h (trough level) after administration of opioid maintenance therapy. Results showed that patients at trough level had a significantly higher percentage of incorrect reactions (p = 0.03) and more simple errors (p = 0.02) than patients at peak level as well as methadone-maintained patients at peak level tended to perform less well than buprenorphine-maintained patients in some of the test items, e.g. methadone-maintained patients at trough level had a higher number of delayed reactions in the RST3 phase 2 test (p = 0.09) and answered fewer questions correctly in the visual structuring ability test (p = 0.04). This investigation indicates that opioid-maintained patients did not differ significantly at peak vs.trough level in the majority of the investigated items and that both substances do not appear to affect traffic-relevant performance dimensions when given as a maintenance therapy in a population where concomitant consumption would be excluded.

Prevalence and Distribution of Hepatitis C Subtypes in Patients with Opioid Dependence

Aim and Setting: The drug addiction out-patient clinic at the University Hospital for Psychiatry in Vienna performed a study to identify the prevalence of hepatitis C virus (HCV) infections in a group of opiate-dependent patients, to detect the distribution of HCV subtypes and to calculate the comorbidity of human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Design and Participants: We consecutively investigated unselected patients (n = 173) during an observation period of 2 months with the diagnosis of opioid dependence (DSM-IV: 304.0) and polysubstance dependence (DSM-IV: 304.9). Measurements: Blood was investigated focusing on liver enzymes and on viral status including HIV, hepatitis B and hepatitis C, followed by subtyping of the virus. Findings: In 80.3% hepatitis C antibodies were found, 66.5% were HCV RNA (PCR) positive. 3a was the most frequent subtype (35.6%), followed by 1a (28.8%) and 1b (22.0%). Four patients had both subtypes 1a and 1b (6.8%), 3 were 2b positive (5.1%) and 1 patient had subtypes 2a/2c (1.7%). No significant difference in aspartate (AST) and alanine aminotransferases (ALT) concerning the different subtypes (AST: p = 0.290; ALT: p = 0.260) could be calculated; 11.6% showed co-infection with HIV, 2 patients had a chronic infection with hepatitis B. Conclusions: The rate of HCV infection in substance-dependent patients at our drug addiction out-patient clinic is extremely high. The distribution of subtypes showed a relatively homogeneous distribution of the types 1a, 1b and 3a. The recommended therapy with α-interferon should be initiated in drug-dependent patients under considerations of an enrollment in oral maintenance with synthetic opioids.

Maintenance therapy with synthetic opioids within a multidisciplinary program – A stabilizing necessity for pregnant opioid dependent women

SummaryAims: Drug addiction in females requires special attention when the woman is pregnant. In opioid dependent pregnant addicts early intervention during the prenatal period is highly desirable for maintaining the health of the woman, the fetus, and her infant after birth. The aim of our study was to perform an analysis of different variables to determine which factors are responsible for stabilizing the mother so that she could keep the child. Design: Ninety-eight pregnant opioid dependent women who were seeking treatment in our multiprofessional treatment program were investigated. Setting: The addicts were treated during pregnancy and then after delivery for an investigational period of 36 months at the University Drug Addiction Out-patient Clinic. Participants: Pregnant women who met DSM-IV criteria for opioid dependence (DSM-IV 304.0) or polysubstance dependence (DSM-IV 304.8) were included; 82 children were born during this time-frame. Intervention: All patients received oral opioid maintenance therapy (methadone, slow-release morphine, buprenorphine) and had access to the same psychosocial and psychotherapeutical treatment. Measurements: Length of treatment period, duration of maintenance therapy, type of maintenance therapy as well as attendance of psychotherapy were used to evaluate which of these parameters are predictors of whether the child can live with its own mother or had to be placed elsewhere. Findings: At the end of our investigation period, 59% (n = 48) of the children were still raised by their mothers. Duration of involvement in a maintenance program with replacement opioids (p = 0.002), as well as early intervention (p = 0.03) had a significant influence towards retaining custody of the child. In addition to successful pharmacological treatment, psychosocial and psychotherapeutical services influenced the outcome in respect of mothers keeping the child. Conclusion: Early intervention and effective multiprofessional treatment approaches facilitated a better outcome for this population at risk with respect to mothers retaining custody of their child.

Opioid plasma concentrations in methadone- and buprenorphine-maintained patients

This is the first trial to compare the relationship of opioid plasma concentrations in methadone‐versus buprenorphine‐maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient Clinic at the University of Vienna. Of these, 44 (11 female and 33 male) were included in the analyses of plasma concentrations. Subjects received either daily sublingual buprenorphine (2mg or 8mg tablets; maximum daily dose: 8mg) or oral methadone (racemic R‐/S‐methadone) and were maintained on a stable dose after an induction period of 2 weeks. Mean dose and mean plasma concentrations were correlated on an individual and collective basis. Correlation was 0.51 for buprenorphine, whereas the score for methadone was 0.69. Intra‐individual variation was much higher for buprenorphine (p < 0.0001), while the concentration‐to‐dose ratio was very small. Based on the differences of the pharmacokinetics of blood plasma of the two agents, we tried to explain the differences in the acceptance of treatment, which was significantly lower in the buprenorphine‐maintained group. No such differences could be evaluated between completers and dropouts in buprenorphine‐maintained subjects, neither concerning withdrawal scores nor dose, plasma concentration, concentration‐to‐dose ratios or intra‐individual variation.