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Alcohol & Alcoholism Vol. 45, No. 2, pp. 214–216, 2010
Advance Access publication 18 January 2010
Disulﬁram, an Option for the Treatment of Pathological Gambling?
Jochen Mutschler1,3,*, Mira Bühler1, Martin Grosshans1, Alexander Diehl2,
1Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Square J 5 68159 Mannheim,
Germany, 2Department of Psychiatry, Klinikum Braunschweig, Salzdahlumer Str. 90, Braunschweig, Germany and 3University Hospital Zurich, Department of
General and Social Psychiatry, Militärstrasse 8, P.O. Box 1930, CH-8021 Zürich
*Corresponding Author: University Hospital Zurich, Department of General and Social Psychiatry, Militärstrasse 8, P.O. Box 1930, CH-8021 Zürich, Switzerland.
Tel: +41-(0)44-296-7393; Fax: +41-(0)44-296-7469; E-mail: firstname.lastname@example.org
(Received 21 September 2009; in revised form 9 November 2009; accepted 24 December 2009)
Abstract — Aim: Pathological gambling and comorbid alcohol dependence often occur in combination. Disulﬁram is one of theproven drugs for alcohol dependence. In addition to its inhibiting acetaldehyde dehydrogenase, disulﬁram inhibits dopamine β-hydroxylase and may thereby increase dopamine and decrease norepinephrine cerebral concentrations. Because there may becommon neurochemical substrates and neuronal circuits for pathological gambling and addiction, we wished to explore the eﬀectof disulﬁram in gambling. Method: We describe the outcome of a patient with alcohol dependence and pathological gamblingtreated with disulﬁram D. Results: During treatment with disulﬁram, the patient reported that his desire to gamble disappearedentirely. Follow-up indicated that he has not gambled for >12 months. Conclusions: Although uncontrolled case observations
should be interpreted with caution, disulﬁram deserves further investigation in pathological gambling.
Recent evidence indicates that similar mechanisms are in-
volved in PG and drug addiction. Neuroimaging data suggest
Pathological gambling (PG) is a public health problem char-
that in PG and drug addiction, the same brain areas are in-
acterized by recurrent and pathological patterns of gambling.
volved. Reduced activity in the ventral striatum and the
PG is associated with a range of social and psychological pro-
ventromedial and ventrolateral prefrontal cortex has been re-
blems like high rates of bankruptcy, divorce, suicide and
ported in PG, which is also a hallmark of drug addiction
reduced quality of life. Although the lifetime prevalence rate
of pathological gambling in the German population is 0.2–
gamblers found that gambling elevated dopamine levels in
0.4%, it often remains unrecognized and, therefore, untreated
problem gamblers more than in healthy controls (
). The mesocorticolimbic dopaminergic system has
gambling and other psychiatric disorders are very common. In
been found to be implicated in rewarding and reinforcing be-
particular, high comorbidity rates have been reported between
haviours. It has been suggested that PG might be related to a
PG and drug dependence. Rates vary from 34 to 80% for sub-
deﬁciency of the mesocorticolimbic dopaminergic reward sys-
stance use disorders (excluding tobacco) (;
tem, as has been shown for drug addiction.
Another hallmark of drug addiction that also holds for path-
dependent patients is at least three times higher than in the
ological gambling is the inability to inhibit inappropriate
general population ). In cocaine-dependent
responses. Accumulating evidence points towards an impor-
patients, lifetime comorbidity rates have been reported that
tant role of brain dopamine and noradrenergic systems in
are even ﬁve times higher as in the general population (
impulsive behaviour. The inferior frontal gyrus is critically in-
These observations suggest that common patho-
volved in response inhibition and might be particularly
physiological factors might underlie PG and drug addiction.
impacted by the brain’s noradrenergic system.
However, this hypothesis is not proven yet.
Other preclinical studies suggest that engaging in casino gam-
PG is currently classiﬁed as an ‘impulse control disorder
bling elevates activity of the hypothalamic–pituitary axis in
(ICD) not elsewhere categorized’ in the DSM, although the
problem and non-problem gamblers, as indicated by increased
current diagnostic criteria indeed share many features with
plasma levels of norepinephrine, cortisol and increased heart
those for drug dependence, including (i) continued engage-
rate. Roy and colleagues found higher levels of norepineph-
ment in a behaviour despite adverse consequences, (ii)
rine or its metabolites in urine, blood or cerebrospinal ﬂuid
diminished self-control over engagement in the behaviour,
(iii) compulsive engagement in the behaviour and (iv) an ap-
The similarities between PG and drug addiction suggest
petitive urge or craving state prior to engaging in the
that patients with pathological gambling may also beneﬁt
behaviour as well as tolerance and withdrawal (
from medication used for the treatment of drug addiction.
). Similarities between PG and drug dependence
Pharmacotherapy research and validated treatment options
include not only phenomenological criteria but also epidemi-
for PG are limited. At the present time, there is no medication
ological, clinical, genetic and neurobiological characteristics
for treatment of PG that is approved by the Food and Drug
Administration. Controlled clinical trials provide some evi-
PG might best be characterized as a non-substance-related
dence for beneﬁcial eﬀects of opiate antagonists (naltrexone
or behavioural addiction with a compulsive urge for a non-
The Author 2010. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved
Disulfiram in the Treatment of Pathological Gambling
and selective serotonin reuptake inhibitors, which have
hol had disappeared but that he surprisingly had no urge to
been shown to reduce craving for gambling. Additionally, cog-
nitive behavioural therapy has been shown to be an eﬀective
In conclusion, we found that, since initiating the supervised
treatment for some patients with PG. However, all these thera-
treatment with disulﬁram, the patient has been abstinent from
alcohol and gambling for >12 months.
Disulﬁram is well known as a treatment for alcohol depen-
dence (e.g. ; Disulﬁram also helps in the
treatment of cocaine addiction (; possibly by reducing cocaine craving by
This case report suggests that disulﬁram might provide treat-
increasing neurotransmitter levels of dopamine and decreasing
ment in PG. Disulﬁram helps in the treatment of alcoholism,
the norepinephrine levels by blocking the activity of the en-
cocaine addiction, human cancers and fungal infections
zyme dopamine beta hydroxylase (DBH) involved in the
For more than half a century, disulﬁram has been successfully
used for alcohol aversion therapy (Disulﬁr-
neurochemical disturbances have been reported in PG, disul-
am’s pharmacokinetics have been extensively studied; it
ﬁram might not only be eﬀective in the treatment of cocaine
also has a good safety record (). It is a well-
addiction but also in the treatment of PG (
known vicious circle that substance use may lead to more
gambling and more gambling may lead to substance use. Per-
We present a case in which a patient with PG and comorbid
sonality traits like impulsivity and reward sensitivity may
alcohol dependence was treated with disulﬁram. We suggest
contribute to excessive engagement in both behaviours.
that disulﬁram has the potential to reduce craving and patho-
In the presented case, the patient has abstained from alcohol
consumption for >12 months now and, notably, he has notgambled either since treatment with disulﬁram started. Onepossible explanation might be that the patient was abstinent
from alcohol. However, it can be argued that the patient
was treated for alcohol dependence several times, but PG
Mr K. is a 48-year-old married male working as a part-time
was never markedly aﬀected. Furthermore, despite numerous
nurse. His alcohol dependence developed 25 years ago. He
previous detoxiﬁcations, the patient had never been treated
also started problematic gambling at slot machines at around
the same time. He met all of the criteria for PG according to
Psychological aspects of the supervised disulﬁram therapy
DSM-IV and ICD-10 for ∼20 years. The patient has no crim-
and the high placebo response rate seen in treatment studies of
inal history, but has run up about 10,000 euros in debts due to
pathological gambling may have contributed to the good clin-
PG. Mr K is a smoker and nicotine-addicted but has never tak-
ical outcome, and this is a methodological limitation of this
He was treated for alcohol dependence for the ﬁrst time
However, we propose that a possible neurobiological con-
∼10 years ago. He has undergone 28 inpatient detoxiﬁcations.
tributant might be that disulﬁram directly modulates reward
In 2000, he had long-term residential treatment for alcohol de-
sensitivity and craving for gambling by increasing the level
pendence. Afterwards, he participated in a self-help group on
of the brain chemical dopamine and decreasing the norepi-
a regular basis but did not receive speciﬁc treatment for PG.
nephrine levels through blocking the activity of the DBH,
He remained completely abstinent from alcohol for 6–7
months. However, he continued to gamble during those alco-
, ). Most strikingly, these two neurotransmitter
systems are thought to be altered in PG (;
After the ﬁrst contact with our team in 2008, he was treated
for 5 weeks in our inpatient department, which specializes in
The disappearance of the patient’s desire to gamble during
addiction medicine. The treatment included behavioural ther-
treatment with disulﬁram points towards the potential of disul-
apy as well as relapse prevention medication with disulﬁram
ﬁram in reward modulation in PG, similar to that described in
(dosage 500 mg/3 days per week). The patient tolerated the
medication without any side eﬀects (apart from short-term,
). Our preliminary clinical data support the hypothesis
moderate fatigue at the beginning of the treatment).
that disulﬁram aﬀects the desire to gamble, thereby promoting
After discharge from our inpatient treatment, we continued
gambling abstinence. The possible involvement of DBH was
treating the patient over a period of 12 months in our outpa-
tient programme for chronic alcohol patients. The disulﬁram
Previous studies in drug-dependent patients and patients
medication was supervised by a physician three times per
with PG have shown that a combination of pharmacological
week, establishing a therapeutic ritual with high frequency
treatment in combination with psychosocial treatment meth-
of short-term individual contacts. During this therapeutic rit-
ods, group therapies or contingency management therapies
ual, the therapist praised the patient for taking disulﬁram and
is more eﬀective than either treatment alone (
for maintaining abstinence, thereby providing continuous rein-
forcement of an alcohol-free lifestyle. Additionally, alternative
the potential of combined treatment approaches using disulﬁ-
coping skills were developed and breathalyzer tests to monitor
ram and cognitive behavioural therapies are necessary.
abstinence from alcohol were conducted. Throughout this
In summary, this report suggests that disulﬁram might be
treatment, the patient reported that not only craving for alco-
a promising pharmacological agent in the treatment of PG.
Future studies should assess the eﬃcacy of disulﬁram in redu-
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