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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. Copyright (c) 2007 S. Karger AG, Basel.

Wiener klinische Wochenschrift, 2006, 118(17-18): 521-30
[Cocaine abuse in Vienna and European cities--a multi-center study]
A. Bawert, N. Primus, R. Jagsch, H. Eder, M. Zanki, K. Thau and G. Fischer

INTRODUCTION: As cocaine consumption seems to have increased over the last decades, the EU has funded this multi-center, cross-sectional survey to investigate cocaine consumption in three different target groups. The study was conducted by the Addiction Clinic, Department of Psychiatry, Medical University Vienna and other nine European cities. METHODS: Data were collected by structured face-to-face interviews. The sample was composed of 211 cocaine abusers out of three target groups: (1) treatment group undergoing opioid maintenance therapy, (2) marginalized scene group and (3) integrated party group. Sociodemographic data such as age, education, employment, monthly expenses on cocaine/crack, data on consumption patterns, physical and mental health and personal needs regarding cocaine consumption were evaluated. Urine toxicology results for cocaine in the treatment group completed the analysis. RESULTS: The marginalized scene group was the oldest with a mean age of 29.35 years, with the highest unemployment rate (mean 25.11 days) and the longest duration of cocaine consumption (mean 5.80 years). They had the highest cocaine consumption pattern with a mean of 22.32 days within the last month. On average 1969 Euros/months was spent for their addiction. The treatment group had the lowest school education with a mean of 10.36 years, but showed a sufficient insight in their cocaine problem. However, the party group (with the lowest mean age, 25.64 years) highly underestimated their drug problem, the mean amount of money they spent for their addiction was 588.99 Euro/months. Structured urine toxicology between 1996 and 2002 in patients undergoing opioid maintenance therapy ("treatment group") revealed a significant increase of concomitant cocaine consumption (1996: 33.1%; 2002: 40.2%; p = 0.044). DISCUSSION: The European trend of increased cocaine use could also be observed in Vienna. One of the greatest barriers for establishing adequate treatment settings for this target group is the difficulty to reach this population. In addition, multiple substance abuse seems to be one of the predominating patterns of cocaine consumption and this aspect should be integrated within treatment (in the treatment and scene groups additional heroin and benzodiapzepines abuse is observed, in the party group intensive alcohol consumption). The Viennese results are in line with those of the other European cities; however, it could not be confirmed that consumption of crack cocaine and binge play a similarly significant role as in cities such as Hamburg or London.

Addict Biol. 2005 Dec;10(4):365-71. 
Opioid plasma concentrations in methadone-and buprenorphine-maintained patients.
Jagsch R, Gombas W, Schindler SD, Eder H, Moody DE, Fischer G.

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.

Addiction. 2005 Aug;100(8):1101-9. 
Comment in: Addiction. 2005 Dec;100(12):1758-9.
Comparative study of the effectiveness of slow-release morphine and methadone
for opioid maintenance therapy.
Eder H, Jagsch R, Kraigher D, Primorac A, Ebner N, Fischer G.

AIMS: Slow-release morphine may represent a much-needed new pharmacological
treatment for opioid dependence. DESIGN: In a 14-week randomized, double-blind,
double-dummy, cross-over study oral slow-release morphine was compared with
methadone as a treatment for opioid dependency. During two study periods, each
consisting of a 1-week titration and a 6-week fixed-dose treatment phase,
medication was administered daily under supervised conditions. SETTING: The
study was carried out at the Addiction Clinic, Department of Psychiatry, Medical
University Vienna. PARTICIPANTS: Sixty-four subjects (56 males, eight females)
with opioid dependence participated in the trial. MEASUREMENTS: Efficacy was
evaluated on the basis of retention, use of illicit substances based on
urinalysis, extent of drug cravings, withdrawal symptoms and general wellbeing.
Safety was assessed on the basis of adverse events and clinical and physical
examination. Demographic and baseline characteristics were assessed using the
European Addiction Severity Index. FINDINGS: Fifty-five patients (86%) completed
the study, with a mean methadone dose of 85 mg and a mean slow-release morphine
dose of 680 mg. No significant differences in retention or use of illicit
substances (opioids, benzodiazepines, cocaine) were observed, irrespective of
treatment group or medication. However, patients receiving slow-release morphine
had significantly lower depression (P < 0.001) and anxiety scores (P = 0.008)
and fewer physical complaints (P < 0.001). CONCLUSIONS: Oral slow-release
morphine is as effective as methadone in the treatment of opioid dependency,
with comparable safety and tolerability and a greater benefit on patient
wellbeing. Greater pharmaceutical diversity represents a modern development in
mainstream medicine. Slow-release morphine might represent a future treatment
option that will improve long-term outcomes for this target group.

Eur Addict Res. 2005;11(3):145-51. 
Use of slow-release oral morphine for the treatment of opioid dependence.
Kraigher D, Jagsch R, Gombas W, Ortner R, Eder H, Primorac A, Fischer G.

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.

Eur Addict Res. 2004;10(2):80-7. 
Maintenance therapy with synthetic opioids and driving aptitude.
Schindler SD, Ortner R, Peternell A, Eder H, Opgenoorth E, Fischer G.

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. Copyright 2004 S. Karger AG, Basel

Wien Klin Wochenschr. 2002 Nov 30;114(21-22):904-10. 
[Slow-release morphine hydrochloride for maintenance therapy of opioid
dependence] [Article in German]
Kraigher D, Ortner R, Eder H, Schindler S, Fischer G.

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.

Addiction. 2003 Jan;98(1):103-10. 
Neonatal outcome following buprenorphine maintenance during conception and
throughout pregnancy.
Schindler SD, Eder H, Ortner R, Rohrmeister K, Langer M, Fischer G.

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.

Psychiatr Prax. 2001 Sep;28(6):267-9. 
[Buprenorphine in pregnancy] [Article in German]
Eder H, Rupp I, Peternell A, Fischer G.

The treatment of opioid dependence during pregnancy is a major challenge for
doctors, social workers and gynaecologists. Continuous drug abuse during
pregnancy can lead to a variety of complications in the mother, fetus and
neonate. lt is recommended practice to maintain pregnant opioid-dependent women
with synthetic opioids and according to international guidelines, methadone is
the recommended substance so far. However, a neonatal abstinence syndrome (NAS)
of varying severity is observed in 60 - 80 % of the neonates with even a longer
course of duration in comparison to the NAS after heroin consumption during
pregnancy. NAS is characterised by tremor, irritability, hypertonicity,
vomiting, sneezing, fever, poor suckling, and sometimes convulsions. Recent
studies have investigated the safety and efficacy of other synthetic opioids
like sublingual buprenorphine for the treatment of pregnant patients. We present
a 22 year old opioid-dependent woman, who has been maintained continuously on
buprenorphine for 3 years. During the treatment episode she delivered two
healthy newborns and both did not show any symptoms of NAS. The maintenance
therapy with buprenorphine proved safety and efficacy during pregnancy, the
mother was free of continuous heroin abuse, verified through supervised
urine-toxicology. The quantitative and qualitative difference in NAS may be
explained by the partial mu-receptor agonist and kappa-antagonist receptor
profile of buprenorphine compared to pure mu-agonist action of methadone or
heroin.

Eur Addict Res. 2000 Dec;6(4):198-204. 
Prevalence and distribution of hepatitis C subtypes in patients with opioid
dependence.
Gombas W, Fischer G, Jagsch R, Eder H, Okamoto I, Schindler S, Muller C, Ferenci
P, Kasper S.

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 alpha-interferon should be initiated in drug-dependent patients
under considerations of an enrollment in oral maintenance with synthetic
opioids.

Addiction. 2000 Feb;95(2):239-44. 
Treatment of opioid-dependent pregnant women with buprenorphine.
Fischer G, Johnson RE, Eder H, Jagsch R, Peternell A, Weninger M, Langer M,
Aschauer HN.

AIMS: To assess the maternal and fetal acceptability of buprenorphine and
neonatal abstinence syndrome (NAS) in children born to buprenorphine-maintained
mothers. DESIGN AND SETTING: Open-label, flexible dosing, inpatient induction
with outpatient maintenance, conducted at the University of Vienna within the
existing pregnancy and drug addiction program. PARTICIPANTS: Fifteen
opioid-dependent pregnant women. INTERVENTION: Sublingual buprenorphine tablets
(1-10 mg/day). MEASUREMENTS: Mothers: withdrawal symptoms (Wang Scale), nicotine
dependence (Fagerstrom Scale: FTQ) and urinalysis. Neonates: birth outcome and
NAS (Finnegan Scale). FINDINGS: All subjects were opioid-, nicotine- and
cannabis-dependent. Buprenorphine was well tolerated during induction (Wang
Score < or = 4) and illicit opioid use was negligible (91% opioid-negative). All
maternal, fetal and neonatal safety laboratory measures were within normal
limits or not of clinical significance. Mean birth outcome measures including
gestational age at delivery (39.6 +/- 1.5 weeks), Apgar scores (1 min = 8.9; 5
min = 9.9; and 10 min = 10), birth weight (3049 +/- 346 g), length (49.8 +/- 1.9
cm) and head circumference (34.1 +/- 1.8 cm) were within normal limits. The NAS
was absent, mild (without treatment) and moderate (with treatment) in eight,
four and three neonates, respectively. The mean duration of NAS was 1.1 days.
CONCLUSIONS: Buprenorphine appears to be well accepted by mother and fetus, and
associated with a low incidence of NAS. Further investigation of buprenorphine
as a maintenance agent for opioid-dependent pregnant women is needed.

Addiction. 1999 Sep;94(9):1337-47. 
Buprenorphine versus methadone maintenance for the treatment of opioid
dependence.
Fischer G, Gombas W, Eder H, Jagsch R, Peternell A, Stuhlinger G, Pezawas L,
Aschauer HN, Kasper S.

AIMS: To evaluate the effectiveness of buprenorphine compared with methadone
maintenance therapy in opiate addicts over a treatment period of 24 weeks.
DESIGN: Subjects were randomized to receive either buprenorphine or methadone in
an open, comparative study. SETTING: Subjects were recruited and treated at the
drug addiction outpatient clinic at the University of Vienna. PARTICIPANTS:
Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid
dependence and were seeking treatment. INTERVENTION: Subjects received either
sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral
methadone (racemic D -/+ L-methadone; maximum daily dose 80 mg). A stable dose
was maintained following the 6-day induction phase. MEASUREMENT: Assessment of
treatment retention and illicit substance use (opiates, cocaine and
benzodiazepines) was made by urinalysis. FINDINGS: The retention rate was
significantly better in the methadone maintained group (p < 0.05) but subjects
completing the study in the buprenorphine group had significantly lower rates of
illicit opiate consumption (p = 0.04). CONCLUSION: The results support the
superiority of methadone with respect to retention rate. However, they also
confirm previous reports of buprenorphine use as an alternative in maintenance
therapy for opiate addiction, suggesting that a specific subgroup may be
benefiting from buprenorphine. This is the first comparative trial to use
sublingual buprenorphine tablets: previously published comparison studies refer
to 30% solutions of buprenorphine in alcohol.

Wien Med Wochenschr. 1999;149(11):331-6. 
[Interdisciplinary therapeutic approaches with substance abusers taking into
consideration gender differences] [Article in German]
Fischer G, Eder H.

Scientific advances over the past 20 years have shown that drug addiction is a
chronic, relapsing disease that results from the prolonged effects of drugs on
the brain. As with many other brain diseases, addiction includes behavioral and
social-context aspects that are important parts of the disorder itself.
Therefore, the most effective treatment approaches will include biological,
behavioral and social-context components. Whereas the basic treatment approach
in substance dependence involves the medical field, psychosocial support is the
second main area which has to be included in order to gain a successful
treatment outcome. In addition, psychotherapy presents a third useful area in
the field of the treatment of drug addiction, but only under the consideration
that the addict shows a continuing motivation to change. Recognizing addiction
as a chronic, relapsing brain disorder characterized by compulsive drug seeking
and use can impinge on society's overall health and social policy strategies and
help diminish the health and social costs associated with drug abuse and
addiction. Treatment of substance dependence in men differs from treatment of
substance dependence in women; drug addiction in females requires special
attention when the woman is pregnant.

Nervenarzt. 1999 Sep;70(9):795-802. 
[Buprenorphine vs. methadone as maintenance treatment for opioid dependence] 
[Article in German]
Fischer G, Gombas W, Eder H, Jagsch R, Stuhlinger G, Aschauer HN, Kasper S.

The efficacy of buprenorphine in opioid dependent patients (n = 20) was compared
to methadone maintained subjects (n = 20) in a randomized comparison trial.
Sublingual application of buprenorphine as an alternative synthetical opioid is
being compared to methadone during a 24 week study period. A trend (p = 0.06)
could be found in the retention rate of investigated patients being maintained
on a mean dosage of 63 mg oral applicable methadone (racemat of L- and
D-methadone) in comparison to the group on a mean dosage of 7.3 mg buprenorphine
(sublingual tablets). The dropout-rate of 11 subjects at the end of the study in
the buprenorphine group was higher when compared to the dropout-rate of 5 in the
methadone group. There was no significant difference between the two groups over
the treatment period in respect to additional consumption of opiates,
benzodiazepines and cocaine as evaluated through urine toxicology. The result in
regard to compliance over the study period demonstrates that methadone appears
to be the more successful oral opioid (p = 0.04). Nevertheless, efficacy of
buprenorphine in maintenance could be demonstrated in the remaining subjects,
and further studies with higher daily doses and a higher number of subjects have
to be performed.

Addiction. 1999 Feb;94(2):231-9. 
Comparison of methadone and slow-release morphine maintenance in pregnant
addicts.
Fischer G, Jagsch R, Eder H, Gombas W, Etzersdorfer P, Schmidl-Mohl K, Schatten
C, Weninger M, Aschauer HN.

AIMS: To investigate whether the neonatal abstinence syndrome (NAS) is different
in children born to women maintained on slow-release morphine, compared with
those maintained on methadone, and to compare additional drug consumption in
these groups of women. DESIGN, SETTING AND PARTICIPANTS: An open, randomized
trial was conducted in an established clinic. Forty-eight pregnant women who
presented to the clinic as opiate or polysubstance abusers were enrolled and
maintained on either methadone (24 women) or slow-release morphine (24 women) up
to and following delivery. The programme included psychosocial therapy and
support for their opiate-addicted partners. MEASUREMENTS: Standard urinalysis
methods were used to measure consumption of cocaine and benzodiazepines during
pregnancy. Injection sites were monitored to indicate additional opiate use. NAS
was measured according to Finnegan score and the amount of phenobarbiturates
prescribed to alleviate the symptoms. FINDINGS: No difference was found in the
number of days that NAS was experienced by neonates born to methadone or
morphine maintained mothers (mean = 16 and 21 days, respectively). All children
were born healthy and no serious complications arose. Fewer benzodiazepines (p <
0.05) and fewer additional opiates (p < 0.05) were consumed by the
morphine-maintained women compared with those who took methadone, but no
difference was seen in cocaine consumption. Nicotine consumption was reduced
significantly in both groups during pregnancy (p < 0.02). CONCLUSIONS: Both
methadone and morphine are suitable maintenance agents for pregnant opiate
addicts. Maintenance agents that result in a less prolonged NAS should be
studied in further trials.

Acta Neurol Scand  1999 Jan;99(1):48-53 
Postural control and lifetime alcohol consumption in alcohol-dependent patients.
Wober C, Wober-Bingol C, Karwautz A, Nimmerrichter A, Deecke L, Lesch OM.

OBJECTIVES: The aim of this study was to examine the relationship between
alcohol consumption and postural control in alcohol-dependent patients. MATERIAL
AND METHODS: Posturographic measurements were performed in 82 abstinent patients
and in 54 healthy controls. The findings in the patients were compared with
those in the controls as well as with the daily alcohol consumption, the
consumption during 6 months before the admission for alcohol withdrawal therapy
and the estimated lifetime alcohol consumption. RESULTS: Postural control was
impaired in alcohol-dependent patients compared to healthy controls. This
impairment was related with the lifetime alcohol consumption, but not with the
alcohol consumption per day and prior to admission, respectively. Comparing
healthy controls, and alcohol-dependent patients with an estimated lifetime
alcohol consumption of < 1000 kg and > or = 1000 kg revealed a significant
increase in 6 of 8 sway parameters. Furthermore, the lifetime alcohol
consumption increased significantly from patients with normal posturographic and
clinical findings to those with abnormalities in both examinations. CONCLUSION:
This study suggests that postural imbalance in abstinent alcohol-dependent
patients is related to the lifetime alcohol consumption.

Eur Addict Res. 1998 Dec;4(4):198-202. 
Outpatient opiate detoxification treatment with buprenorphine. Preliminary
investigation.
Diamant K, Fischer G, Schneider C, Lenzinger E, Pezawas L, Schindler S, Eder H.

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.

Psychiatry Res. 1998 Sep 28;83(3):139-47. 
Cerebral CT findings in male opioid-dependent patients: stereological,
planimetric and linear measurements.
Pezawas LM, Fischer G, Diamant K, Schneider C, Schindler SD, Thurnher M, Ploechl
W, Eder H, Kasper S.

Cerebrospinal fluid (CSF) space enlargement has been demonstrated in
substance-related disorders like alcohol and cocaine dependence. Experimental
animal studies showed a reduction in shape and size of mesolimbic dopaminergic
neurons after chronic morphine administration. Other studies indicated a change
of neurofilament and glial fibrillary acid proteins after chronic opiate
administration. Furthermore, frequent overdosing and toxicological effects of
'street'-heroin may lead to CSF space enlargement in opioid dependence. In our
study the pericortical and ventricular CSF space of 21 male opioid-dependent
patients was compared with an age- and sex-matched normal control group.
Considering serious problems with ratio and proportion measures, we used a
battery of linear (cella media index, Huckman number, frontal horn index),
planimetric (cortical atrophy score) and stereological volumetric measures in
order to detect differences in cranial computerized tomography scans. We found a
significant ventricular and cortical volume loss of the brain in
opioid-dependent patients. A higher degree of frontal lobe volume loss seemed to
be associated with a shorter period of abstinence before relapse. However, the
etiology of volume loss of the brain in opioid-dependent patients is still
unclear, but experimental animal studies provide some evidence that long-term,
chronic opiate exposure is associated with visible changes of specific
structures in the brain.

Alcohol Alcohol  1998 Jul-Aug;33(4):393-402 
Ataxia of stance in different types of alcohol dependence--a posturographic
study.
Wober C, Wober-Bingol C, Karwautz A, Nimmerrichter A, Walter H, Deecke L.

The aim of this study was to assess the prevalence of ataxia of stance in
different types of alcohol-dependent patients. Posturographic measurements were
performed in 82 abstinent alcohol-dependent patients and 54 healthy controls in
order to analyse postural control. According to Lesch and co-workers, alcohol
dependence was classified as total abstinence (Type I), drinking without loss of
control (Type II), fluctuating course (Type III), and persistent severe drinking
(Type IV). The mechanisms of alcohol dependence in these subtypes can be
summarized as follows: Type I patients drink alcohol to counteract symptoms of
alcohol withdrawal; Type II patients use alcohol as an agent for solving
conflicts; Type III patients drink alcohol to 'treat' an affective disorder; and
Type IV patients have a history of pre-alcoholic neurological and/or psychiatric
disorders. The neurological examination showed pathological findings in 39%,
whereas posturographic measurements uncovered impaired postural control in 61%
(chi2 = 8.8, P = 0.003). Comparing the different study groups revealed that
ataxia of stance was most common in alcohol-dependent patients classified as
Type IV (tau = 0.24, P = 0.005). In conclusion, posturographic measurements are
superior to the clinical examination in detecting postural imbalance in
alcohol-dependent patients. The prevalence of postural imbalance is highest in
patients classified by Lesch as Type IV. Consequently, this type of alcohol
dependence -- characterized by pre-alcoholic neurological and/or psychiatric
disorders, bears the highest risk of developing ataxia of stance.

Psychiatry Res. 1998 Sep 28;83(3):139-47. 
Cerebral CT findings in male opioid-dependent patients: stereological,
planimetric and linear measurements.
Pezawas LM, Fischer G, Diamant K, Schneider C, Schindler SD, Thurnher M, Ploechl
W, Eder H, Kasper S.

Cerebrospinal fluid (CSF) space enlargement has been demonstrated in
substance-related disorders like alcohol and cocaine dependence. Experimental
animal studies showed a reduction in shape and size of mesolimbic dopaminergic
neurons after chronic morphine administration. Other studies indicated a change
of neurofilament and glial fibrillary acid proteins after chronic opiate
administration. Furthermore, frequent overdosing and toxicological effects of
'street'-heroin may lead to CSF space enlargement in opioid dependence. In our
study the pericortical and ventricular CSF space of 21 male opioid-dependent
patients was compared with an age- and sex-matched normal control group.
Considering serious problems with ratio and proportion measures, we used a
battery of linear (cella media index, Huckman number, frontal horn index),
planimetric (cortical atrophy score) and stereological volumetric measures in
order to detect differences in cranial computerized tomography scans. We found a
significant ventricular and cortical volume loss of the brain in
opioid-dependent patients. A higher degree of frontal lobe volume loss seemed to
be associated with a shorter period of abstinence before relapse. However, the
etiology of volume loss of the brain in opioid-dependent patients is still
unclear, but experimental animal studies provide some evidence that long-term,
chronic opiate exposure is associated with visible changes of specific
structures in the brain.

Eur Addict Res. 1998;4 Suppl 1:3-7. 
Comparison of buprenorphine and methadone maintenance in opiate addicts.
Eder H, Fischer G, Gombas W, Jagsch R, Stuhlinger G, Kasper S.

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 micro-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.

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