Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study.

AIMS: To evaluate the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women. DESIGN: Randomized, double-dummy, double-blind, flexible-dosing comparison study. SETTING: Addiction Clinic at the Medical University of Vienna, Austria. PARTICIPANTS: Eighteen women were assigned randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six in the methadone and eight in the buprenorphine group). INTERVENTION: Sublingual buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day), with matched placebos. MEASUREMENTS: Mothers: retention in treatment, urine toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence syndrome (NAS) in severity and duration. FINDINGS: There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group (P = 0.047).Neonates: There was earlier onset of NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); 43% did not require NAS-treatment with short treatment duration in both groups (mean 5 days). CONCLUSION: This preliminary study had limited power to detect differences but the trends observed suggest this kind of research is practicable and that further studies are warranted.

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.

Buprenorphine maintenance: office-based treatment with addiction clinic support.

INTRODUCTION: Buprenorphine has already been registered in 27 European countries for maintenance therapy in opioid-dependent patients. In our office-based prescription study we applied sublingual buprenorphine, initiating the treatment at the addiction clinic with subsequent treatment at the offices of general practitioners (GPs) to evaluate its efficacy and feasibility in two different treatment settings. METHODS: Sixty opioid-dependent patients were studied for a period of 15 weeks. The first 3 weeks of treatment initiation took place at the addiction clinic, followed by 12 weeks of treatment by GPs. Mean outcome measures were retention rate and additional consumption of illicit substances in addition to the evaluation of whether buprenorphine can be prescribed successfully by GPs. RESULTS: The retention rate was 57% (n = 34). No significant differences occurred between the treatment phases at the specialized addiction unit and the GPs' offices. During the 15-week period a significant improvement in well-being and a significant reduction in craving for heroin (p < 0.001) and cocaine (p < 0.001) could be calculated for patients stabilized on a mean dose of 16 mg buprenorphine. Furthermore a significant reduction in additional consumption of opioids (p < 0.001) was found. DISCUSSION: Our results show the involvement of office-based prescription, which should further encourage colleagues to treat opioid-dependent subjects with buprenorphine to make more treatment options for this target group available.

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.

Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy.

AIMS: To assess the effects of maternal buprenorphine treatment at conception and during pregnancy on neonates in terms of birth outcomes and neonatal abstinence syndrome (NAS). DESIGN AND SETTING: Prospective, open-label, out-patient maintenance, case report study, conducted at the drug addiction out-patient clinic at the University Hospital Vienna. PARTICIPANTS: Two buprenorphine-maintained pregnant women who had conceived during buprenorphine treatment. Both patients had previously given birth to healthy neonates following induction on to buprenorphine maintenance therapy in the second trimester. MEASUREMENTS: Mothers: urinalysis. Neonates: gestational age at delivery, Apgar scores, birth weight, length and NAS (Finnegan Scale). FINDINGS: Urinalyses were negative for both women for 25 and 38 months, respectively, during the pregnancy period. There were no complications during the course of the pregnancy. The newborns delivered by both women were healthy, birth outcomes were within normal ranges and there were no NAS symptoms requiring treatment. CONCLUSIONS: To our knowledge this is the first report detailing the pregnancies of women treated with buprenorphine at the time of conception and investigated in a prospective study. The NAS noted in neonates born to buprenorphine-maintained mothers appears to be less severe than the NAS observed in neonates born to methadone-maintained mothers. These preliminary data indicate that, in our patient cohort, buprenorphine maintenance at the time of conception and during pregnancy did not seem to affect birth outcome measurements such as pregnancy complications, week of delivery, birth weight, length, umbilical pH or neurodevelopmental progress. Future prospective studies with larger study populations are warranted.

[Slow-release morphine hydrochloride for maintenance therapy of opioid dependence]. / Retardiertes Morphinhydrochlorid in der Erhaltungstherapie Opioidabhängiger.

INTRODUCTION: In Austria, methadone, buprenorphine as well as oral slow-release morphine are used for the treatment of opioid dependence. This controlled examination marks the first time that oral slow-release morphine hydrochloride is applied for maintenance therapy in opioid dependent subjects. METHODS: In order to evaluate the effectiveness of this psychopharmacological medication, we examined patients over a three-week period. Outcome measures were retention rate, additional consumption and the evaluation of opioid withdrawal 24 hours after the last oral medication. RESULTS: Sixty-seven patients were included; sixty-four patients completed the study, representing a retention rate of 94%. During the three-week period, a significant improvement in well-being and a significant reduction in heroin, cocaine and benzodiazepine craving (p < 0.0001) was evaluated. Furthermore, there was a significant reduction of additional consumption of benzodiazepines in supervised urinalysis. Additional consumption of cocaine remained unchanged. Laboratory results showed a significant reduction of CK over the course of investigation. DISCUSSION: The high retention rate of 94% implies a good acceptance and efficacy of the substance. The reduced CK is consistent with a reduction in intravenous application of illegal substances. However, randomized double-blind, double-dummy studies with oral slow-release morphine are needed in order to meet criteria for evidence based medicine.