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Background Due to potential proarrhythmic side-effects levo-α-Acetylmethadol (LAAM) is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. Methods ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1) during a run-in period with all patients on methadone and 2) 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. Results Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group). No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409 s ± 0.022 s versus 0.418 s ± 0.028 s, p = 0.046), whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1). Conclusions In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended under LAAM medication.

Background The P300 component of the auditory evoked potential is an indicator of attention dependent target processing. Only a few studies have assessed cognitive function in substituted opiate addicts by means of evoked potential recordings. In addition, P300 data suggest that chronic nicotine use reduces P300 amplitudes. While nicotine and opiate effects combine in addicted subjects, here we investigated the P300 component of the auditory event related potential in methadone substituted opiate addicts with and without concomitant non-opioid drug use in comparison to a group of control subjects with and without nicotine consumption. Methods We assessed 47 opiate addicted out-patients under current methadone substitution and 65 control subjects matched for age and gender in an 2-stimulus auditory oddball paradigm. Patients were grouped for those with and without additional non-opioid drug use and controls were grouped for current nicotine use. P300 amplitude and latency data were analyzed at electrodes Fz, Cz and Pz. Results Patients and controls did not differ with regard to P300 amplitudes and latencies when whole groups were compared. Subgroup analyses revealed significantly reduced P300 amplitudes in controls with nicotine use when compared to those without. P300 amplitudes of methadone substituted opiate addicts were in between the two control groups and did not differ with regard to additional non-opioid use. Controls with nicotine had lower P300 amplitudes when compared to patients with concomitant non-opioid drugs. No P300 latency effects were found. Conclusion Attention dependent target processing as indexed by the P300 component amplitudes and latencies is not reduced in methadone substituted opiate addicts when compared to controls. The effect of nicotine on P300 amplitudes in healthy subjects exceeds the effects of long term opioid addiction under methadone substitution.

Background: An eHealth computer-based tool named ORION was constructed to assist patients in the clinic to appreciate the factors responsible for risks of drug overdose. The aim of this study was to investigate the associations between risk perception of overdose, engagement in the ORION tool and willingness to alter overdose risk factors. Methods: 194 opioid dependent patients participated from 4 countries (UK, N=39; Germany, N=99; Italy, N=40 and Denmark, N=16).A structural equation model was fitted (AMOS version 17) to summarise the predicted associations between perceived risk and willingness to change risks of opioid overdose. The degree of engagement with the tool (time spent and number of changes to overdose risk factors) was explored. Results: A variety of models were fitted and the most parsimonious model provided a non-significant difference between the raw data and the specified model: Chi Sq = 16.87, df10, p = .077chi sq/df = 1.688. The fit indices: CFI = .991, RMSEA = .066. Pre and post self-assessments of risk towards known factors linked with overdose were highly correlated. A significant path was found between engagement in the tool and the willingness to change one or more risk factors (stand. coeff. = 0.16, p = .04). In addition, the final assessment of the risk factors was associated with engagement (stand. coeff. = 0.18, p = .02). Conclusion: The encouragement of drug users to engage in exploring changes to their overdose risk when presented on a computer screen appears to increase willingness to change risky behaviour. Publisher PDF

This study was done in order to examine the hypothesis that so-called ultra-rapid opiate detoxification provides a mild, short, and safe withdrawal. A total of 22 patients who were addicted to opiates exclusively underwent ultra-rapid detoxification. Each patient was pretreated with methadone. During general anesthesia lasting about six hours with methohexital or propofol, naloxone was administered with doubling of the dose every 15 minutes with a starting bolus dose of 0.4 mg. The total bolus dose of 12.4 mg, delivered within 60 minutes, was followed by a naloxone infusion of 0.8 mg/h until the next morning. On the day of anesthesia naltrexone (50 mg/d) treatment was initiated. When withdrawal symptoms occurred, specific medications, e.g., clonidine, were added. After determining baseline values, withdrawal symptoms were investigated during a further four weeks by means of established clinical scales. The results document marked withdrawal symptoms for at least one week after detoxification. The intensity of withdrawal symptoms during the first seven days of treatment was significantly (p