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.

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 (2 mg or 8 mg tablets; maximum daily dose: 8 mg) 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.

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.

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder.

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.

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.

A longitudinal view of triggers and thresholds of suicidal behavior in depression.

BACKGROUND: Recurrent brief depressive disorder (RBD) and major depressive disorder (MDD) share the same diagnostic picture of full-blown depression and are both associated with increased suicide attempt rates. However, longitudinal diagnostic shifts from RBD to MDD or vice versa, called "combined depression" (CD), have demonstrated a substantially higher risk of suicide attempts in epidemiologic and clinical studies. Following the stress-diathesis model of suicidal behavior, we compared possible triggers and thresholds for suicidal behavior among patients with RBD, MDD, and CD. RBD and MDD diagnoses were based on DSM-IV criteria. Furthermore, the goal of this study was to determine if impulsivity as an underlying factor could explain high suicide attempt rates in CD. METHOD: A structured clinical interview evaluating comorbid Axis I and II disorders and RBD and a battery of instruments assessing suicidal behavior were administered to 101 patients with RBD (N = 27), MDD (N = 33), or CD (N = 41). RESULTS: Patients with CD showed significantly higher (p < .05) scores on measures of suicidal behavior in comparison with RBD and MDD patients. Together with comorbid substance abuse and marital status, CD was among the highest-ranking risk factors for suicide attempts. Impulsivity was identified as a major underlying factor, predicting 80.7% of suicide attempts. CONCLUSION: CD seems to be an important clinical risk factor for the prediction of suicide attempts, similar to risk factors such as substance use disorders and borderline personality disorder. All of these factors share the same diathesis for increased impulsivity and suicidal ideation, which could explain comorbidity and suicidal behavior. The coexistence of a greater propensity for suicidal ideation and impulsivity in RBD might also explain why such patients are more prone to attempt suicide, even if they do not, in the case of RBD, meet the duration criteria for MDD.

Paranoid delusions and hallucinations and bright light therapy in Alzheimer's disease.

INTRODUCTION: Bright light therapy (BLT) is becoming increasingly popular as an adjunct in the treatment of non-SAD depression and circadian rhythm disturbances in demented patients. Although the rate of side-effects is low, special attention should be paid when treating new groups of patients. We present the case of an 80-year-old woman suffering from dementia of Alzheimer's type (DAT). METHOD: Bright light (2.500 lux) was administered two hours daily between 10 and 12 a.m. for 14 days. Changes in delusion or agitation were recorded using the confusion rating scale (CRS). RESULTS: Out of five patients, three already had delusional symptoms which slightly improved during the course of BLT, one patient never showed delusions before or during BLT, and one patient, which we present here, showed an increase in agitation and developed delusional symptoms. After eight days of treatment, the patient developed conjunctival irritation with marked red eyes and complained about blurred vision. After 12 days of treatment, the patient was disorientated in time and place and after 14 days the patient started to hallucinate and BLT had to be discontinued. The paranoid delusions and hallucinations stopped one day after treatment discontinuation. CONCLUSION: Looking at all the presented evidence, BLT seems to be a useful treatment supplement in DAT patients, when suffering from delusions or agitation. On the other hand, caution should be used when using BLT in demented patients if agitation develops or increases during BLT.

Opioid addiction changes cerebral blood flow symmetry.

Changes in regional cerebral blood flow (rCBF) due to long-term abuse of opioids such as heroin or morphine are not yet fully understood in humans. The goal of the present study was to investigate rCBF alterations in a large sample of long-term opioid addicts in comparison to healthy controls. We investigated 21 opioid-dependent subjects, who were currently abusing heroin or were enrolled in a methadone or morphine maintenance program, and 36 healthy controls with (99m)Tc-HMPAO single photon emission computed tomography. We found a decrease in rCBF in most regions of interest in patients in comparison to controls. Long-term opioid dependence seems to decrease prefrontal CBF in particular. A right-greater-than-left CBF asymmetry in healthy subjects was reversed in patients. This change in CBF symmetry could reflect the different emotional status of opioid-dependent patients. Our findings are in line with neuropsychological investigations indicating a correlation of mood states with lateralization of hemispheric activation patterns.

[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.