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The use of naltrexone in pathological and problem gambling: A UK case series

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Background and aims: To investigate the potential indications and adverse effects of using the opioid antagonist naltrexone to treat problem gamblers. Case presentation: The files of the 1,192 patients who were referred to the National Problem Gambling Clinic between January 2015 and June 2016 were audited. Seventeen patients were considered appropriate for treatment with naltrexone, having attended and failed to respond to psychological therapies at the clinic. Fourteen patients were placed on a regimen of 50 mg/day naltrexone. Discussion: Of the 14 patients who were treated with naltrexone, there were 10 for whom sufficient follow-up existed to analyze the treatment efficacy and side effects of naltrexone. Patients showed significant decreases in their craving to gamble and the majority (60%) were able to abstain completely from gambling in the treatment period, with a further 20% reducing their gambling to almost nothing. The reported side effects from the naltrexone included: loss of appetite, gastrointestinal pain, headaches, sedation, dizziness, and vivid dreams. Two patients with concurrent alcohol-use disorder relapsed during the treatment. One patient relapsed after the treatment period. Conclusions: The study showed significant outcomes in reducing gambling cravings for the sample set. Given the design of the study as a case series, there was no control group, and a number of patients were on other psychotropic medications. We recommend care when prescribing to those suffering from concurrent alcohol-use disorder.
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The use of naltrexone in pathological and problem gambling: A UK case series
SOPHIE WARD
1,2
*, NEIL SMITH
1
and HENRIETTA BOWDEN-JONES
1,3
1
National Problem Gambling Clinic, Central and North West London NHS Foundation Trust, London, UK
2
Institute of Medical and Biomedical Education, St. Georges University of London, London, UK
3
Faculty of Medicine, Imperial College London, London, UK
(Received: September 9, 2017; revised manuscript received: January 28, 2018; second revised manuscript received: August 9, 2018;
accepted: August 10, 2018)
Background and aims: To investigate the potential indications and adverse effects of using the opioid antagonist
naltrexone to treat problem gamblers. Case presentation: The les of the 1,192 patients who were referred to the
National Problem Gambling Clinic between January 2015 and June 2016 were audited. Seventeen patients were
considered appropriate for treatment with naltrexone, having attended and failed to respond to psychological
therapies at the clinic. Fourteen patients were placed on a regimen of 50 mg/day naltrexone. Discussion: Of the 14
patients who were treated with naltrexone, there were 10 for whom sufcient follow-up existed to analyze the
treatment efcacy and side effects of naltrexone. Patients showed signicant decreases in their craving to gamble and
the majority (60%) were able to abstain completely from gambling in the treatment period, with a further 20%
reducing their gambling to almost nothing. The reported side effects from the naltrexone included: loss of appetite,
gastrointestinal pain, headaches, sedation, dizziness, and vivid dreams. Two patients with concurrent alcohol-use
disorder relapsed during the treatment. One patient relapsed after the treatment period. Conclusions: The study
showed signicant outcomes in reducing gambling cravings for the sample set. Given the design of the study as a case
series, there was no control group, and a number of patients were on other psychotropic medications. We recommend
care when prescribing to those suffering from concurrent alcohol-use disorder.
Keywords: naltrexone, gambling disorder, UK
BACKGROUND
Pathological and problem gambling (PG) is a psychiatric
disorder characterized by persistent and recurrent gambling
behavior leading to clinically signicant impairment or
distress (American Psychiatric Association, 2013). Sufferers
tend to become increasingly involved in terms of time and
nancial commitment, continuing to gamble regardless of
the impact on their personal, social, and nancial well-being
(Hodgins, Stea, & Grant, 2011). There is a lack of remission
in PG, despite psychological intervention. PG is known to
have a negative impact on physical and mental health,
occupation, nancial matters, and interpersonal relation-
ships (Grant & Kim, 2001). There is a signicant relation-
ship between PG and comorbid psychiatric disorders, where
they are likely to have a mutually reinforcing effect on the
sufferer. Attempted or completed suicide is not uncommon
(Ledgerwood & Petry, 2004).
The UK Gambling Commission (2017) reported that, as
of December 2016, 48% of people had participated in
gambling in the past 4 weeks, an increase from 43% in
December 2015. The commission reported that 0.7% of
respondents identied as problem gamblers, amounting to
there being around 300,000 problem gamblers in the UK at
any one time. Those in the 18- to 24-year-old-age group are
least likely to gamble, with 33% reporting having partici-
pated in the past 4 weeks, versus 54% for the highest
participant group (4554 years old people). However, these
young gamblers are almost twice as likely to be a problem
gambler, with 1.1% estimated to be so. Framing National
Health Service (NHS) treatment policy is particularly im-
portant, provided the risks of this vulnerable group and the
ease of accessing gambling online. It is one of the aims of
this study to help in guiding such policy.
Naltrexone is a US Food and Drug Administration
(FDA)- and National Institute for Health and Care Excel-
lence (NICE)-approved treatment for alcohol and opiate
dependence (Center for Substance Abuse Treatment,
2009). In preclinical data, naltrexone is advocated to help
treat addictions more diversely by blocking binding of
endogenous opioids. The suggested role of gambling in the
stimulation of the endogenous opioid system forms the
clinical basis for using opioid antagonists in the treatment
of PG (Grant, Odlaug, & Schreiber, 2014). Indeed, this is the
basis of its use in behavioral addictions more broadly
* Corresponding author: Sophie Ward; National Problem Gam-
bling Clinic, Central and North West London NHS Foundation
Trust, Cranmer Terrace, London SW17 0RE, UK; E-mail:
m1700129@sgul.ac.uk
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License,
which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and
source are credited, a link to the CC License is provided, and changes if any are indicated.
ISSN 2062-5871 © 2018 The Author(s)
CASE REPORT Journal of Behavioral Addictions 7(3), pp. 827833 (2018)
DOI: 10.1556/2006.7.2018.89
First published online September 21, 2018
(Grant, Schreiber, & Odlaug, 2013). In a randomized con-
trolled trial on kleptomania, it was found that subjects
randomized to receive naltrexone reported signicant reduc-
tions in urges in stealing and stealing behavior (Grant, Kim,
& Odlaug, 2009). A case series looking at compulsive
buying found that high-dose naltrexone led to partial or
complete remission of urges to shop (Grant, 2003). A
systematic review of the use of naltrexone in diverse
behavioral addictions showed consistent efcacy of the
drug (Aboujaoude & Salame, 2016).
The body of literature on the pharmacological treatment
of PG is supportive of the use of opioid antagonists as a
treatment of last resortonce psychological interventions
have failed. Grant et al. (2014) reviewed 18 randomized
control trials across ve drug classes in the treatment of PG.
Antidepressants, mood stabilizers, and atypical antipsycho-
tics have shown mixed results, and there is no evidence to
recommend their use as a treatment protocol in PG. The
literature demonstrates a higher treatment efcacy with
opioid antagonists (Grant, Kim, & Odlaug, 2007). The
earliest clinical indication for using naltrexone in PG came
from a single case report of a pathological gambler with a
13-year history of alcohol dependence. Signicant reduc-
tions in scores measuring compulsive drinking and compul-
sive gambling were observed (Crockford & el-Guebaly,
1998). We reviewed the evidence from three randomized
control trials that specically looked at the efcacy of daily
naltrexone in PG (Kim & Grant 2001;Kim, Grant, Adson,
& Shin, 2001;Grant, Kim, & Hartman, 2008), nding
signicant reductions in gambling outcomes in all three.
We also reviewed two as needed(pro re nata) studies
(Lahti, Halme, Pankakoski, Sinclair, & Alho, 2010;
Kovanen et al., 2016), nding more mixed results. For
completeness, we reviewed studies of another opioid antago-
nist, nalmefene. Grant et al. (2006) showed signicant reduc-
tions in gambling urges; however, a later trial suggested that
only those patients on high doses reported reductions in the
primary outcome measure (Grant, Odlaug, Potenza,
Hollander, & Kim, 2010). It was on this basis that it was
decided to treat our patients with a daily dose of naltrexone.
To date, there has been no research performed in the UK
on the use of naltrexone in PG. There have been no NICE
guidelines for the treatment of PG; thus, as elsewhere, UK
clinicians have been referring to the Monash guidelines.
According to GambleAware, only 2.7% of those affected by
PG are in treatment at any one time, compared with 6% of
problem drinkers and 50% of Class A drug misusers. Given
the psychosocial and medical impact of PG, we believe that
parity of esteem in its treatment with other mental health
issues is required, including in pharmacological interven-
tion. As such, we saw value in a case series discussion for
patients who had been pharmacologically treated with nal-
trexone in the UK. Our ndings add credibility to the
international evidence base on the pharmacological treat-
ment of PG, which is still limited.
The pharmacokinetic safety of naltrexone indicates that it
is a well-tolerated drug, with transient and self-limiting side
effects (Foss et al., 1997). Naltrexone is known to cause
overdose symptoms, if used simultaneously as opioids. The
British National Formulary notes that naltrexone is contra-
indicated in patients suffering from hepatic or renal
impairment (Joint Formulary Committee, 2015). These are
important areas of clinical monitoring.
CASE PRESENTATION
The case series was performed through a retrospective audit
of the case les of the 1,192 patients who attended the
National Problem Gambling Clinic in the 18-month period
between January 2016 and June 2017. Five hundred and
sixteen of these patients entered treatment, of which 17 were
screened as appropriate for treatment with naltrexone.
Naltrexone was indicated for severely affected patients,
as measured by the Problem Gambling Severity Index
(PGSI). These patients had already undergone psychologi-
cal therapy for PG at the National Problem Gambling Clinic
(NPGC) with limited success. The severity of their craving
to gamble was measured again at the naltrexone assessment
using the Gambling Craving Scale (GCS). It was conrmed
at this stage that the patient was committed to either abstain
from or dramatically reduce their gambling behavior. Only
patients with normal liver and renal function tests and who
would be able to avoid abuse of alcohol throughout the
treatment period were considered. Patients with an existing
recreational or prescription use of opiates were also exclud-
ed, due to the risk of overdose. Out of the 17 patients, 14 had
commenced treatment.
The treatment commencement dates for the patients in
the sample set fell between January 2016 and April 2017.
Patients were prescribed an initial dose of 25 mg per day for
3 days, and then 50 mg per day as the usual maintenance
dose. Details of other support services, such as Gamblers
Anonymous, as well as information on the potential side
effects of naltrexone were provided to the patients. Any
patient-reported side effects or unintended treatment out-
comes of the naltrexone were recorded.
Patients were called for follow-up after 6 weeks, where a
further GCS was answered as well as a reective question-
naire on the patients experience of treatment. If the treatment
suited the patient, a further prescription of the maintenance
dose was offered for 8 weeks, after which prescribing was
handed-over to the patients general practitioner.
Of the 14 cases, there were 10 for whom sufcient
follow-up existed to enable a meaningful analysis of the
efcacy of their treatment. These patients are summarized in
Table 1. The information considered adequate was the
presence of a complete psychosocial and forensic history,
information on comorbidities and other addictions, gam-
bling history, history of past treatment modalities, a cor-
rectly completed GCS for both prior to and 6 weeks
following commencement of treatment with naltrexone, and
the reective questionnaire. There were a further two cases
for whom answers to the reective questionnaire were
available. We comment on the responses to this question-
naire at the end of the discussion.
Of the 10 patients, 8 were male and 2 were female. The
ages of the patients ranged from 29 to 56 years, with a
median age of 44 years. These patients had gambling careers
spanning from 3 to 40 years, with a median career length of
21 years. The patients reported estimated total losses (ETLs)
of between £5,000 and £1,700,000, with the majority having
828 |Journal of Behavioral Addictions 7(3), pp. 827833 (2018)
Ward et al.
Table 1. Summary of pathological and problem patients treated with naltrexone for whom there existed a full complement of follow-up materials
Age,
Sex
Referral
route
Gambling
career
(years) ETL
PGSI
(/27)
Medical
comorbidities
Psychiatric
comorbidities
Other
addictive
pathologies
Reported
medications Social history
Forensic
history
Treatment
goal
Pre-
treatment
GCS (/30)
Post-
treatment
GCS (/30)
Naltrexone
side effects
Reported
gambling
activity
1 43, M GP 17 £1,700,000 27 Hypercholesterolerria
Angina
Schizophrenia History of
cocaine
abuse
Risperidone
4mg Divorced, lives alone,
three children (no
contact),
unemployed,
reported domestic
violence, and poor
relationship with
family
Six custodial
sentences
related to
gambling,
longest
6 years
Abstinence 30 9 None Gambled a small
ticket on two
occasions in
the rst
3 weeks
Abstained
from the fourth
week of
treatment
Recurrent urinary tract
Lipomas
Citalopram
20 mg
Atorvastatin
20 mg
2 56, F Psychiatrist 3 £5,000 19 Raised alanine
transaminase and
night seizures
Bipolar
affective
disorder
None reported Aripiprazole
20 mg
Lives with daughter
(30), physically
abused by mother,
and raped by brother
at 13
None reported Reduction 28 6 Loss of
appetite
One episode of
PG in 7 weeks.
Now does the
Euromillions
once a week
£9, which was
her treatment
goal
3 29, M Past patient 5 £100,000 21 None reported None reported None reported None
reported
Weekly binge
drinking and cocaine
use
Stealing to
fund
gambling
Reduction 7 4 Stomach
pains
None
4 45, M Self-
referral
25 None
reported
23 None reported None reported Alcohol and
cocaine
None
reported
Use of MDMA, family
history of gambling,
brother PG, and
facial disgurement
None reported Abstinence 27 3 Evening
tiredness
None during
treatment
period. Report
of relapse
afterward
5 47, F Past patient 30 £10,000 22 Osteoarthritis,
hypertension, and
Crohns disease
Depression and
obsessive and
compulsive
traits
None reported Sertraline
150 mg
Spent time in care as
child, father PG and
alcoholic,
unemployed, with
adult children
None reported Abstinence 30 7 Rapid pulse
rst few
days
None
6 37, M From
inpatient
unit
25 £1,000,000 14 None reported Obsessive
compulsive
traits
None reported None
reported
No signicant family
history, having
young children
Under
investigation
for missing
stock at
work
Abstinence 28 5 Stomach
pains,
dizziness,
nausea,
and
headaches
for the rst
few days
None
(Continued)
Journal of Behavioral Addictions 7(3), pp. 827833 (2018) |829
Naltrexone in pathological and problem gambling
Table 1. (Continued)
Age,
Sex
Referral
route
Gambling
career
(years) ETL
PGSI
(/27)
Medical
comorbidities
Psychiatric
comorbidities
Other
addictive
pathologies
Reported
medications Social history
Forensic
history
Treatment
goal
Pre-
treatment
GCS (/30)
Post-
treatment
GCS (/30)
Naltrexone
side effects
Reported
gambling
activity
7 54, M Self-
referral
40 £300,000 12 Hypertension Attention-
decit
hyperactivity
disorder
Pomography,
shopping,
and eating
Citalopram
30 mg
Divorced, taxi driving
creates temptation,
having two young
children
None reported Abstinence 27 13 Nausea for
the rst
few days
None
8 31, M Self-
referral
15 £60,000 27 None reported Anxiety and
depression
None reported None
reported
Heavy social drinking
housed by social
services, three
children by two
mothers, and
umemployed
None reported Abstinence 7 0 None None
9 47, M Self-
referral
30 £500,000 23 None reported Depression Alcohol Citalopram
20 mg
Two brothers with
drug addictions,
single and living
alone, beaten by
father as child
Signicant
forensic
history
Abstinence 27 17 Stomach
cramps,
vivid
deams,
headaches
Relapse had a
relapse of his
alcoholism and
failed to take
the naltrexone
10 34, M GP 14 None
reported
12 None reported Depression Alcohol,
heroin,
tramadol,
and codeine
Single, in care as a
child, previously
homelessness, and
unemployed
None reported Abstinence 25 3 Reduced
appetitie,
and
feeling
spaced
out
Relapse
intrusive side
effects and
could not
forsake heavy
drinking
Advised to stop
taking the
naltrexone as a
result
Note. ETL: estimated total loss; PGSI: Problem Gambling Severity Index; GP: general practitioner.
830 |Journal of Behavioral Addictions 7(3), pp. 827833 (2018)
Ward et al.
signicant personal indebtedness as a consequence of their
losses. The average ETL was £459,375. All of the patients
had already completed, or attempted to complete a previous
gambling-specic treatment modality. These modalities in-
cluded self-exclusion, GamCare counselling, Gamblers
Anonymous, and Gordon Moody. All patients had attended
a previous NPGC psychotherapy or cognitive behavioral
therapy program. The responses to the PGSI before the
commencement of naltrexone ranged from 12/27 to 27/27,
with a median score of 21.5. For eight patients, the treatment
goal was abstinence and for two it was reduction.
Eight of the 10 patients reported diagnosis of an axis I
psychiatric disorder, including schizophrenia, bipolar
affective disorder, attention decit hyperactivity disorder
(ADHD), depressive disorder, or a concurrent addictive
pathology. Six patients were taking another psychotropic
medication, which included antidepressants and
antipsychotics. Four patients reported a chronic medical
comorbidity. All 10 patients had signicant social
history including family breakdown, previous emotional
or sexual abuse by a close friend or family member,
family history of an axis I disorder, unemployment, time
spent in care as a child, and homelessness. Four of the
patients had a history of illegal activity in order to fund
their gambling.
The reported side effects of the naltrexone were loss of
appetite, gastrointestinal pain, sedative symptoms or feeling
spaced out,headaches, nausea, dizziness, and vivid
dreams. The majority of side effects resolved within the
rst week. Unintended treatment outcomes included re-
duced anger, reduced impulsiveness, improvement in mood,
improved concentration, less compulsion to overexercise,
less interest in overeating, and increased calmness.
As demonstrated in Table 1, all 10 patients experienced a
reduction in cravings to gamble as tested by the pre- and
post-commencement GCS. Responses to the pre-
commencement GCS ranged from 7/30 to 30/30, with a
median score of 27, making the median patient at very high
riskof gambling. Responses to the 6-week follow-up GCS
ranged from 0/30 to 17/30, with a median score of 5.5,
representing a low riskof gambling. Of the 10 patients, 6
were able to abstain completely for the whole treatment
period. Of the four who did not abstain, gambling behavior
was much reduced in two cases. Two patients relapsed. One
had a relapse of alcoholism and failed to continue taking the
naltrexone. One was experiencing intrusive side effects,
decided they could not forsake heavy drinking and was
advised to stop taking the naltrexone as a result. One patient
was reported to have relapsed after being discharged at the
end of the treatment period.
The reective questionnaire of the 12 naltrexone-
consumed patients provided further color on the treatment
response:
11 said they had gambled less since started consuming
naltrexone.
10 said they had experienced less gambling-related
thoughts and urges.
8 said they had experienced side effects.
10 said it had not been difcult to stick to the treatment.
Of those answering yes,one had found it hard to
abstain from opiate-based painkillers and one found it
hard to avoid alcohol-binges as well as struggling with
the side effects.
When asked whether there had been any overall impact
on their day-to-day life, four cited a positive effect, one
a mixed effect, one specied that they had experienced
an effect but did not specify any details, and six
reported no impact.
All 12 said they would recommend naltrexone to
someone else facing gambling difculties.
Ethics
The study procedures were carried out in accordance with
the Declaration of Helsinki. All subjects were informed
about the study and provided informed consent.
DISCUSSION
The patient set was small and heterogeneous in terms of
presenting comorbidities, concurrent medication, and psy-
chosocial history, yet we observed marked improvement in
craving-to-gamble in all cases. In the context of the literature
to date, we view that our results with this sample of patients
from the NPGC give support of the use of naltrexone as an
adjunct treatment in PG.
We were not able to control for the presence of comor-
bidities and other psychotropic medications. We were not
able to comment on the effect of dosage, given that each
patient was given the same treatment regimen. However, the
review of Grant et al. (2008) suggested that 50 mg/day was
as efcacious in treating PG as higher doses, which was the
basis of the decision to use 50 mg/day in the study. We were
not able to provide any evidence of the effect of naltrexone
on gambling urges and behavior following cessation of
treatment, although a 12-month follow-up study showed
that the majority (60%) of patients did not relapse within
6 months of stopping naltrexone (Dannon, Lowengrub,
Musin, Gonopolsky, & Kotler, 2007). There is a scope for
a randomized control trial over a longer period of time to
ascertain long-term treatment outcomes and the tolerability
of the treatment medically and psychologically, especially
once cessation has occurred.
To date, although evidence suggests that naltrexone has
the most potential as a pharmacological treatment for PG,
there has been no formal comparison study of its efcacy
vis-à-vis other opioid antagonists in PG, notably nalmefene.
A comparative study of naltrexone and nalmefene was
conducted by Drobes, Anton, Thomas, and Voronin
(2003), testing their respective effects on alcohol consump-
tion, showing that the efcacy was similar to each medica-
tion. The results suggested that the side effect burden was
lesser in the case of naltrexone. Once opioid antagonists are
established as a treatment modality for PG, a comparative
study between the two drugs for specicefcacy in PG
would be worthwhile.
We found that alcohol consumption seemed to increase
the treatment resistance of a patients PG, based upon the
relapses of the heavy drinkers in the sample set. Baron and
Dickerson (1999) found that alcohol consumption signi-
cantly increases impairment in control of gambling
Journal of Behavioral Addictions 7(3), pp. 827833 (2018) |831
Naltrexone in pathological and problem gambling
behavior. Further work to investigate this relationship would
be useful in order to inform treatment protocol for PG
suffers who also drink heavily.
We believe that NICE guidelines are now required to
address a pathology that affects almost half a million people
in the UK, but that has not been given parity of esteem with
other mental health disorders by the NHS. The introduction
of naltrexone as a last resorttreatment for those who have
been resistant to psychological therapies seems logical,
given its approval by both the FDA and NICE for other
addictive pathologies and the benets it has shown for PG in
the evidence, to date, further supported by our work at the
NPGC.
Funding sources: This study was supported by Central and
North West London NHS Foundation Trust.
Authorscontribution: SW: conception and design of work;
acquisition, analysis, and interpretation of data; and drafting
of work. HB-J: conception and design of work, critical
revision, clinical investigation, provided, and cared for
study participants; NS: conception and design of work,
clinical investigation, provided, and cared for study
participants.
Conict of interest: None.
Acknowledgements: The authors would like to thank
Andrew Bayston (Assistant Psychologist, NPGC) for con-
tribution to data acquisition and clinical provision.
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Naltrexone in pathological and problem gambling
... Our review found no evidence that interventions for harmful gambling have been tested using experimental research designs, such as RCTs [33,34] in a UK context. The overreliance on either retrospective chart reviews (employing secondary analysis of existing data) or single-subject case reports indicate that treatment-oriented researchers may lack the resources necessary to conduct large-scale, direct comparison of the effectiveness of different treatments for gambling-related problems. ...
... The finding of Louderback et al. [66] that gambling industry-funded experimental studies were more likely to include a power analysis may indicate a greater need for perceived objectivity given the controversial nature of the role of industry funding in gambling research. While our findings cannot directly speak to this issue given, we only identified non-experimental, UK-based treatment studies, only two of the eight studies listed funding details [26,34], and of these only Roberts et al. [26] reported conflicts of interest and receipt of previous sources of funding. One must therefore assume that the remaining studies either did not obtain funding or the reporting requirements of the journals did not specify providing the funding source. ...
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Background Understanding and treating the harm caused by gambling is a growing international psychiatric and public health challenge. Treatment of gambling harm may involve psychological and pharmacological intervention, in conjunction with peer support. This scoping review was conducted to identify, for the first time, the characteristics and extent of United Kingdom (UK) based gambling treatment research. We reviewed studies conducted among people seeking treatment for disordered or harmful gambling in the UK, the settings, research designs, and outcome measures used, and to identify any treatment research gaps. Methods Systematic searches of PsycInfo, PsycArticles, Scopus, PubMed, and Web of Science databases were carried out for gambling treatment research or evaluation studies conducted in the UK. Studies were included if they evaluated the effectiveness of an intervention or treatment designed to improve symptoms of harmful or problematic gambling, reported outcomes of interventions on treatment adherence, gambling symptoms, or behaviours using standardised measures, were conducted in the UK, and were published since 2000. Results Eight studies met the inclusion criteria. Four were retrospective chart reviews, two were single-participant case reports, one described a retrospective case series, and one employed a cross-sectional design. None used an experimental design. Conclusion The limited number of studies included in this review highlights a relative paucity of gambling treatment research conducted in UK settings. Further work should seek to identify potential barriers and obstacles to conducting gambling treatment research in the UK.
... Several studies show that agents that block the opioid system can decrease gambling behavior (37). Nevertheless, it is crucial to note that there is currently no officially approved medication for the treatment of GD. ...
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This narrative review aims to examine pharmacological treatment modalities for gambling disorder (GD) by analyzing recent literature and identifying significant trends in the field. A thorough examination of relevant literature, focusing primarily on recent studies and reviews, in order to identify significant pharmacological treatment approaches and current trends. Results: The review identifies several pharmacological approaches for GD, including opioid antagonists, serotonergic agents, dopaminergic modulators, glutamatergic agents, and mood stabilizers. Recent studies suggest that opioid antagonists such as naltrexone and nalmefene show promise in reducing gambling urges and behaviors. Additionally, serotonergic agents like selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in alleviating the impulsivity and compulsivity associated with GD. Dopaminergic and glutamatergic agents, while showing some potential, require further investigation for their role in GD treatment. Mood stabilizers, particularly lithium, appear to be beneficial, especially in individuals with co-occurring bipolar affective disorder. Pharmacological interventions play a crucial role in the management of GD, with opioid antagonists and SSRIs emerging as promising options. However, further research is needed to elucidate the optimal pharmacotherapeutic approach and develop more targeted treatments for GD. Integration of pharmacotherapy with psychotherapeutic interventions may enhance treatment outcomes for individuals with GD.
... Gambling disorder refers to dominant emotional, cognitive, and behavioral patterns. Ward et al., 2018). The most reported psychotherapeutic interventions were cognitive behavioral therapy (CBT, n = 10: Castren et al., 2013;Rossini-Dib et al., 2015;Tarrega et al., 2015;Boughton et al., 2016;Smith et al., 2016Smith et al., , 2018Bouchard et al., 2017;Mallorqui-Bague et al., 2018;Zhuang et al., 2018;Granero et al., 2020), which was delivered either in groups or individually, either face to face (F2F) or digitally. ...
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Introduction Recovery from complex conditions such as gambling disorders (GD) often entail considerable change and require a range of adaptable interventions in the health care system. Outcomes from such avenues to change are influenced by multifarious contextual factors, which are less frequently considered in treatment outcome studies. Accordingly, this scoping review aims to map the level of evidence and explore how contextual factors influence the provision and outcomes of GD interventions. Methods A systematic search in selected health and social science research databases yielded a total of 2.464 unique references. The results were screened in three selection steps—titles (n = 2.464), abstracts (n = 284) and full-text (n = 104). The scoping approach was applied to provide a narrative account of the final included references (n = 34). Results and discussion Findings suggest that the research on GD treatment is in the early stages of development. Additionally, studies on GD interventions are characterized by cultural biases (Region and ethnicity and Gender perspectives), while three key elements are described as successful avenues to recover from GD (Competence, Perception and Utilization). In line with these findings, proposals for future research and treatment designs are made.
... Among these studies, naltrexone, an opioid antagonist used in opioid replacement therapy, was approved by the FDA to treat ethanol dependence [51][52][53]. Naltrexone has also proven to be efficient in the treatment of pathological gambling [54,55]. A partial nicotine agonist or even nicotine used for nicotine dependence has been used successfully in AUD [56], and methadone (an opioid agonist) has shown efficacy in reducing cocaine abuse among opioid-dependent patients [57]. ...
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Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those at risk for at least alcohol use disorder (AUD), a subset of reward deficiency syndrome (RDS), Blum’s group developed the genetic addiction risk severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions, including pain and even bariatric surgery, as a predictor of severe vulnerability to unwanted addictive behaviors, published since 1990 until now. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. Pearson’s χ2 test or Fisher’s exact test was applied to compare the gender, genotype, and allele distribution if available. The statistical analyses found the OR, 95% CI for OR, and the post risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. Prior to these results, the United States and European patents on a ten gene panel and eleven risk alleles have been issued. In the face of the new construct of the “preaddiction” model, similar to “prediabetes”, the genetic addiction risk analysis might provide one solution missing in the treatment and prevention of the neurological disorder known as RDS.
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Amaç: Bu araştırma, kumar oynama davranışı sergileyen bireylerin relaps risklerini belirleyen unsurları incelemeyi amaçlamaktadır. Yöntem: Fenomenolojik bir yaklaşım ve nitel metodoloji kullanılarak yarı yapılandırılmış görüşmeler 13 katılımcı ile gerçekleştirilmiştir. Kumar oynama geçmişinin olması ve en az bir defa kumarı bırakma girişiminde bulunmuş katılımcılar seçilerek relaps süreci deneyimleri betimsel analiz yöntemiyle analiz edilmiştir. Bulgular: Araştırma bulgularına göre “Sosyal ve Çevresel Faktörler”, “Kişisel ve Duygusal Faktörler”, “Finansal Faktörler” olmak üzere üç farklı tema saptanmıştır. Yetersiz aile desteği, kumar oynayan sosyal çevre ile iletişimin kesilmemesi, borçlar, ekonomik krizler yaşamak, kayıpları telafi etmek, stres, kaygı gibi negatif duygusal durumlardan çıkmak, heyecan arayışı, kumar oynama araçlarından gelen teşvikler katılımcıların relaps yaşamalarını etkileyen faktörler olarak tespit edilmiştir. Kumar oynama davranışı tedavisi için relaps önleme programlarının bütüncül bir yaklaşım içermesi gerektiği sonucuna ulaşılmıştır. Sonuç: Araştırma sonucunda aile desteği, sosyal çevrenin etkisi, psikolojik destek ve terapiler, finansal danışmanlık ve para yönetimi becerileri eğitimi gibi faktörler, relaps riskini azaltmada önemli adımlar olarak değerlendirilmektedir.
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Compulsive sexual behavior disorder (CSBD) has recently been recognized as a psychiatric disorder. Pharmacological treatments for CSBD have received little study and thus have limited empirical support. The main objective of the present work is to review existing literature on the efficacy of different drugs on the symptomatology of CSBD, including the subtype of problematic pornography use (PPU). The main pharmacological approaches to treating CSBD have included opioid antagonists (naltrexone and nalmefene), selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, and sertraline), mood stabilizers (topiramate), tricyclic antidepressants (clomipramine), serotonin antagonist and reuptake inhibitors (nefazodone), and N-acetylcysteine. Since people with CSBD may experience different co-occurring disorders, these should be considered when choosing the best pharmacological treatment. Pharmacological therapy for CSBD/PPU has been suggested as an adjunct to psychological therapies, which, for the moment, have the most empirical evidence. However, to evaluate the efficacy of most of the drugs presented in this narrative review, data to date have only been available from case studies. Thus, empirical support is scant and generalizability of results is limited, highlighting the need for more research in this area.
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Introduction: Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment options include psychological and pharmacological interventions. Areas covered: This narrative review explores existing pharmacological treatments for GD. The following classes of medications were considered: opioid-receptor antagonists (e.g. naltrexone and nalmefene), serotonin reuptake inhibitors (e.g. fluvoxamine, paroxetine, sertraline, escitalopram, and citalopram), glutamatergic agents (e.g. N-acetylcysteine (NAC), acamprosate, and memantine), mood stabilizers (e.g. topiramate, carbamazepine, lithium), and other medications (e.g. modafinil, nefazodone, olanzapine, haloperidol, tolcapone, and bupropion). Expert opinion: Due to the limitations of the studies reviewed, solid conclusions regarding the optimal choice of pharmacotherapy for individuals with GD are challenging to draw at this time. Despite some medications, such as naltrexone and nalmefene, showing promising results, efficacy has varied across studies. The review highlights current gaps/limitations, including small sample sizes, limited diversity in participant demographics, the need for exploring different gambling subtypes and treatment responses, high placebo response rates, lack of longer-term longitudinal information, limited investigation of neurobiological correlates and co-occurring disorders, and the importance of implementation research. Further research is needed to address these gaps and explore additional medications, as well as interventions like neuromodulation.
Chapter
Gambling disorder (GD) defines a condition in which a person uses something of value in order to obtain something of a greater value regardless of consequences. GD and addictive disorder share common neurobiological mechanisms, a tolerance to the mood enhancing effect of the behavior, and marked psychosocial impact. GD is more prevalent in patients with a history of trauma or with other addictive disorders. There is no literature about the impact of GD upon the care of organ transplant patients. In this chapter, we are presenting a case history which illustrates the challenges in diagnosing GD as well as the impact GD can have on patients’ participation in post-transplant care.
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Background/aims: Effective treatment strategies are needed for the treatment of pathological gambling (PG). The efficacy of as-needed naltrexone was assessed in a single-centre, randomised, double-blind, placebo-controlled trial. Methods: The participants (n = 101) received either as-needed placebo or naltrexone (50 mg) and psychosocial support for 20 weeks. The primary outcome measure was the severity of PG assessed by the Yale-Brown Obsessive Compulsive Scale adapted for PG (PG-YBOCS). Secondary gambling-related outcome measures included thoughts/urges and behaviour subscales of PG-YBOCS as well as the highest daily expenditure and gambling frequency. In addition, RAND-36 scales of emotional well-being and social functioning were used as outcomes. The results were analysed using the intention-to-treat principle and linear random effects modelling. Results: No significant treatment group differences were found. In an exploratory analysis, emotional well-being increased in a subgroup of participants with AA genotype of opioid receptor, mu 1 (OPRM1) A118G polymorphism (p = 0.02). Conclusion: Overall, the as-needed naltrexone may not provide substantial additional benefit for PG patients receiving psychosocial support. Replication by larger scale studies is warranted to further evaluate naltrexone administration schedules for the treatment of PG and the role of OPRM1.
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Pathological gambling is a disabling disorder experienced by about 1% of adults. We randomised 233 participants (41.6% women) 1:1:1 to nalmefene (20 or 40 mg) or placebo. In analyses performed using an intention-to-treat (ITT) population, nalmefene failed to show statistically significant differences from placebo on primary and secondary outcomes. Post hoc analyses of only participants who received a full titration of the medication for at least 1 week demonstrated that nalmefene 40 mg/day resulted in significantly greater reductions on the primary outcome measure. These findings suggest that medication dosing may be an important consideration in achieving symptom control.
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Addiction is a major public health problem with few efficacious and safe treatments. The goal of this review is to provide an evidence-based assessment of the therapeutic role of the opioid antagonist naltrexone across the addiction spectrum—substance-based and behavioral. The PubMed database was searched for randomized, placebo-controlled clinical trials that investigated the oral or intramuscular long-acting formulation of naltrexone in substance use disorders or behavioral addictions such as pathological gambling, kleptomania, and trichotillomania. Thirty-nine efficacy studies were retrieved, covering alcohol use disorder (n = 22), opioid use disorder (n = 6), nicotine use disorder (n = 5), stimulant use disorder (n = 2), gambling disorder (n = 2), trichotillomania (n = 1), and kleptomania (n = 1). Despite the very different presentations within and between both addiction categories, the data, as a whole, show consistency in favor of naltrexone’s relative efficacy and safety. Given the potential benefit and good tolerability revealed in the studies, the high morbidity associated with addiction, and the dearth of alternate treatments, naltrexone would seem like an underutilized treatment option. Further, naltrexone’s seemingly broad anti-addiction efficacy supports a shared role for brain opioid pathways in the pathophysiology of addiction, broadly defined. More studies investigating the efficacy and tolerability of naltrexone and other opioid modulators are warranted. Studies should also further examine the effect of combining psychotherapy with naltrexone, as well as the potential role of naltrexone in treating comorbid addictions.
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Behavioural addictions are characterized by an inability to resist an urge or drive resulting in actions that are harmful to oneself or others. Behavioural addictions share characteristics with substance and alcohol abuse, and in areas such as natural history, phenomenology, and adverse consequences. Behavioural addictions include pathological gambling, kleptomania, pyromania, compulsive buying, compulsive sexual behaviour, Internet addiction, and binge eating disorder. Few studies have examined the efficacy of pharmacological and psychological treatment for the various behavioural addictions, and therefore, currently, no treatment recommendations can be made.
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OBJECTIVE To examine a possible treatment option for a relatively common and disabling disorder currently lacking a pharmacotherapeutic intervention. METHOD Three patients fulfilling criteria for compulsive buying without comorbidity were treated with naltrexone to reduce urges to shop and shopping behavior. RESULTS Treatment with high-dose naltrexone (100-200 mg/day) led to partial or complete remission of urges to shop and compulsive shopping behavior in all three cases. Discontinuation and re-challenge with the medication provides further support that improvement was due to naltrexone. CONCLUSION Naltrexone in high doses shows promise for the treatment of compulsive buying.
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AIMS: Pathological gambling (PG) is a relatively common and often disabling psychiatric condition characterized by intrusive urges to engage in deleterious gambling behavior. Although common and financially devastating to individuals and families, there currently exist no formally approved pharmacotherapeutic interventions for this disorder. This review seeks to examine the history of medication treatments for PG. METHODS: A systematic review of the 18 double-blind, placebo-controlled pharmacotherapy studies conducted for the treatment of pathological gambling was conducted. Study outcome and the mean dose of medication administered was documented in an effort to determine a preferred medication choice in this population. RESULTS: A variety of medication classes have been examined in the treatment of PG with varying results. Antidepressants, atypical antipsychotics, and mood stabilizers have demonstrated mixed results in controlled clinical trials. Although limited information is available, opioid antagonists and glutamatergic agents have demonstrated efficacious outcomes, especially for individuals with PG suffering from intense urges to engage in the behavior. CONCLUSIONS: Given that several studies have demonstrated their efficacy in treating the symptoms associated with PG, opioid antagonists should be considered the first-line treatment for PG at this time. Most published studies, however, have employed relatively small sample sizes, are of limited duration, and involve possibly non-representative clinical groups (e.g., those without co-occurring psychiatric disorders. Response measures have varied across studies. Heterogeneity of PG treatment samples may also complicate identification of effective treatments. Identification of factors related to treatment response will help inform future studies and advance treatment strategies for PG.
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Gambling disorders, including pathological gambling and problem gambling, have received increased attention from clinicians and researchers over the past three decades since gambling opportunities have expanded around the world. This Seminar reviews prevalence, causes and associated features, screening and diagnosis, and treatment approaches. Gambling disorders affect 0·2-5·3% of adults worldwide, although measurement and prevalence varies according to the screening instruments and methods used, and availability and accessibility of gambling opportunities. Several distinct treatment approaches have been favourably evaluated, such as cognitive behavioural and brief treatment models and pharmacological interventions. Although promising, family therapy and support from Gamblers Anonymous are less well empirically supported. Gambling disorders are highly comorbid with other mental health and substance use disorders, and a further understanding is needed of both the causes and treatment implications of this disorder.
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We explored the efficacy of the opiate antagonist, naltrexone, as a treatment for pathological gambling. Treatment seeking pathological gamblers (n = 39) (according to both South Oaks Gambling Screen and a screen based on the Diagnostic and Statistical Manual of Mental Disorders) participated into our treatment study during 2009. The subjects were instructed to use 50 mg of naltrexone before gambling or when feeling craving towards gambling. The protocol contained one initial doctor visit with motivational brief intervention. During period that were free of gambling, the subjects were instructed to practice other healthy behavioral alternatives to gambling. The primary outcome measure was the Yale Brown Obsessive Compulsive Scale adapted for Pathological Gambling. The other outcome measurements were the EQ-5D quality of life survey, the Alcohol Use Disorders Identification Test, and the Beck Depression Inventory. The average age of the subjects was 39 years; 80% were men. Highly significant (p < 0.01) decreases in reported obsessive-compulsive gambling and depressive symptoms and increases in the subjective quality of life developed in the study. These positive changes suggest that this simple, inexpensive treatment helps pathological gamblers. The role of naltrexone in the treatment effect, however, needs to be determined with a larger, placebo-controlled study.
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Kleptomania is a rare psychiatric disorder characterized by recurrent stealing and for which there exists no empirically validated treatments. This study examined the efficacy and tolerability of the opioid antagonist naltrexone in adults with kleptomania who have urges to steal. An 8-week, double-blind, placebo-controlled trial was conducted to evaluate the safety and efficacy of oral naltrexone for kleptomania. Twenty-five individuals with DSM-IV kleptomania were randomized to naltrexone (dosing ranging from 50 mg/day to 150 mg/day) or placebo. Twenty-three subjects (92%) completed the study. Subjects were assessed every 2 weeks with the Yale Brown Obsessive Compulsive Scale Modified for Kleptomania (K-YBOCS), the urge and behavior subscales of the K-YBOCS, the Kleptomania Symptom Assessment Scale (K-SAS), the Clinical Global Impressions Scale (CGI), and measures of depression, anxiety, and psychosocial functioning. Subjects assigned to naltrexone had significantly greater reductions in K-YBOCS total scores (p = .001), stealing urges (p = .032), and stealing behavior (p < .001) compared with subjects on placebo. Subjects assigned to naltrexone also had greater improvement in overall kleptomania severity (reflected in the CGI scores) (p < .001). The mean effective dose of naltrexone was 116.7 (+/-44.4) mg/day. Naltrexone demonstrated statistically significant reductions in stealing urges and behavior in kleptomania. Naltrexone was well tolerated.
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N-methylnaltrexone bromide (methylnaltrexone) is a quaternary opioid antagonist with a limited ability to cross the blood-brain barrier. In animal models it reverses at peripheral receptors such side effects of opioids as decreased gastrointestinal motility, emesis, and cough suppression without affecting the desired analgesic effect mediated by central nervous system receptors. Methylnaltrexone thus may be a clinically useful compound for the prevention and treatment of opioid-induced side effects. This study was designed to examine the safety and tolerance of methylnaltrexone in healthy human participants over a range of doses and to identify any adverse effects or toxicity associated with methylnaltrexone and the doses at which these adverse effects occur. Healthy male volunteers received intravenous methylnaltrexone in six ascending doses with a placebo randomly inserted into the sequence. Each participant was observed for subjective and hemodynamic changes. Electrocardiogram and laboratory studies were also performed. The dose-limiting adverse effect of methylnaltrexone was orthostatic hypotension at 0.64 mg/kg (n = 3) or 1.25 mg/kg (n = 5), which was transient and self-limiting. Plasma levels of methylnaltrexone in excess of 1,400 ng/mL were observed to be associated with orthostatic hypotension. There were no significant subjective changes, no release of histamine, and no changes in physical examination or laboratory studies during the course of the study. Pharmacokinetic analysis revealed an elimination half-life of 117.5 minutes (+/-53.2), and a clearance of 38.8 L/hr (+/-17.4) with a methylnaltrexone dose of 0.64 mg/kg. Our results indicate that methylnaltrexone is well tolerated at doses of 0.32 mg/kg in healthy humans.