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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
National Problem Gambling Clinic, Central and North West London NHS Foundation Trust, London, UK
Institute of Medical and Biomedical Education, St. Georges University of London, London, UK
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
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:
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.
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
(years) ETL
medications Social history
GCS (/30)
GCS (/30)
side effects
1 43, M GP 17 £1,700,000 27 Hypercholesterolerria
Schizophrenia History of
4mg Divorced, lives alone,
three children (no
reported domestic
violence, and poor
relationship with
Six custodial
related to
6 years
Abstinence 30 9 None Gambled a small
ticket on two
occasions in
the rst
3 weeks
from the fourth
week of
Recurrent urinary tract
20 mg
20 mg
2 56, F Psychiatrist 3 £5,000 19 Raised alanine
transaminase and
night seizures
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
One episode of
PG in 7 weeks.
Now does the
once a week
£9, which was
her treatment
3 29, M Past patient 5 £100,000 21 None reported None reported None reported None
Weekly binge
drinking and cocaine
Stealing to
Reduction 7 4 Stomach
4 45, M Self-
25 None
23 None reported None reported Alcohol and
Use of MDMA, family
history of gambling,
brother PG, and
facial disgurement
None reported Abstinence 27 3 Evening
None during
period. Report
of relapse
5 47, F Past patient 30 £10,000 22 Osteoarthritis,
hypertension, and
Crohns disease
Depression and
obsessive and
None reported Sertraline
150 mg
Spent time in care as
child, father PG and
unemployed, with
adult children
None reported Abstinence 30 7 Rapid pulse
rst few
6 37, M From
25 £1,000,000 14 None reported Obsessive
None reported None
No signicant family
history, having
young children
for missing
stock at
Abstinence 28 5 Stomach
for the rst
few days
Journal of Behavioral Addictions 7(3), pp. 827833 (2018) |829
Naltrexone in pathological and problem gambling
Table 1. (Continued)
(years) ETL
medications Social history
GCS (/30)
GCS (/30)
side effects
7 54, M Self-
40 £300,000 12 Hypertension Attention-
and eating
30 mg
Divorced, taxi driving
creates temptation,
having two young
None reported Abstinence 27 13 Nausea for
the rst
few days
8 31, M Self-
15 £60,000 27 None reported Anxiety and
None reported None
Heavy social drinking
housed by social
services, three
children by two
mothers, and
None reported Abstinence 7 0 None None
9 47, M Self-
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
Abstinence 27 17 Stomach
Relapse had a
relapse of his
alcoholism and
failed to take
the naltrexone
10 34, M GP 14 None
12 None reported Depression Alcohol,
and codeine
Single, in care as a
child, previously
homelessness, and
None reported Abstinence 25 3 Reduced
intrusive side
effects and
could not
forsake heavy
Advised to stop
taking the
naltrexone as a
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
11 said they had gambled less since started consuming
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.
The study procedures were carried out in accordance with
the Declaration of Helsinki. All subjects were informed
about the study and provided informed consent.
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
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
Conict of interest: None.
Acknowledgements: The authors would like to thank
Andrew Bayston (Assistant Psychologist, NPGC) for con-
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Naltrexone in pathological and problem gambling
... 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.
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.
Have you ever lied about your gambling habits to anyone, or tried to conceal the fact you've gambled? Have you ever bet more than you could afford to lose, or gone back the next day to try and win back the money you've lost? Your gambling may be becoming problematic and it's time to seek help. Breaking Free: How to Stop Gambling is a self-help workbook, packed full of practical exercises, worksheets and questionnaires, designed to help you assess the extent of your gambling problem, and develop strategies to combat it. The materials use a cognitive behavioural therapy (CBT) approach to guide you through practical steps and techniques that can help you take back control of your habit. All of the materials have been developed by leading experts in the field and are evidence-based interventions, and are designed to help you to break free from your gambling problem.
Background: Pharmacological interventions for disordered and problem gambling have been employed in clinical practice. Despite the availability of several reviews of the efficacy of pharmacological interventions for disordered or problem gambling, few have employed systematic search strategies or compared different categories of pharmacological interventions. Systematic reviews of high-quality evidence are therefore essential to provide guidance regarding the efficacy of different pharmacological interventions for disordered or problem gambling. Objectives: The primary aims of the review were to: (1) examine the efficacy of major categories of pharmacological-only interventions (antidepressants, opioid antagonists, mood stabilisers, atypical antipsychotics) for disordered or problem gambling, relative to placebo control conditions; and (2) examine the efficacy of these major categories relative to each other. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and PsycINFO (all years to 11 January 2022). Selection criteria: We included randomised trials evaluating a pharmacological intervention for the treatment of disordered or problem gambling. Eligible control conditions included placebo control groups or comparisons with another category of pharmacological intervention. Data collection and analysis: We used standard methodological procedures, including systematic extraction of included study characteristics and results and risk of bias assessment. Our primary outcome was reduction in gambling symptom severity. Our secondary outcomes were reduction in gambling expenditure, gambling frequency, time spent gambling, depressive symptoms, anxiety symptoms, and functional impairment; and responder status. We evaluated treatment effects for continuous and dichotomous outcomes using standardised mean difference (SMD) and risk ratios (RR), respectively, employing random-effects meta-analyses. A minimum of two independent treatment effects were required for a meta-analysis to be conducted (with only meta-analytic findings reported in this abstract). Main results: We included 17 studies in the review (n = 1193 randomised) that reported outcome data scheduled for end of treatment. Length of treatment ranged from 7 to 96 weeks. Antidepressants: Six studies (n = 268) evaluated antidepressants, with very low to low certainty evidence suggesting that antidepressants were no more effective than placebo at post-treatment: gambling symptom severity (SMD -0.32, 95% CI -0.74 to 0.09, n = 225), gambling expenditure (SMD -0.27, 95% CI -0.60 to 0.06, n = 144), depressive symptoms (SMD -0.19, 95% CI -0.60 to 0.23, n = 90), functional impairment (SMD -0.15, 95% CI -0.53 to 0.22, n = 110), and responder status (RR 1.24, 95% CI 0.93 to 1.66, n = 268). Opioid antagonists: Four studies (n = 562) evaluated opioid antagonists, with very low to low certainty evidence showing a medium beneficial effect of treatment on gambling symptom severity relative to placebo at post-treatment (SMD -0.46, 95% CI -0.74 to -0.19, n = 259), but no difference between groups in responder status (RR 1.65, 95% CI 0.86 to 3.14, n = 562). Mood stabilisers: Two studies (n = 71) evaluated mood stabilisers (including anticonvulsants), with very low certainty evidence suggesting that mood stabilisers were no more effective than placebo at post-treatment: gambling symptom severity (SMD -0.92, 95% CI -2.24 to 0.39, n = 71), depressive symptoms (SMD -0.15, 95% CI -1.14 to 0.83, n = 71), and anxiety symptoms (SMD -0.17, 95% CI -0.64 to 0.30, n = 71). Atypical antipsychotics:Two studies (n = 63) evaluated the atypical antipsychotic olanzapine, with very low certainty evidence showing a medium beneficial effect of treatment on gambling symptom severity relative to placebo at post-treatment (SMD -0.59, 95% CI -1.10 to -0.08, n = 63). Comparative effectiveness: Two studies (n = 62) compared antidepressants with opioid antagonists, with very low certainty evidence indicating that antidepressants were no more effective than opioid antagonists on depressive symptoms (SMD 0.22, 95% CI -0.29 to 0.72, n = 62) or anxiety symptoms (SMD 0.21, 95% CI -0.29 to 0.72, n = 62) at post-treatment. Two studies (n = 58) compared antidepressants with mood stabilisers (including anticonvulsants), with very low certainty evidence indicating that antidepressants were no more effective than mood stabilisers on depressive symptoms (SMD 0.02, 95% CI -0.53 to 0.56, n = 58) or anxiety symptoms (SMD 0.16, 95% CI -0.39 to 0.70, n = 58) at post-treatment. Tolerability and adverse events: Several common adverse effects were reported by participants receiving antidepressants (e.g. headaches, nausea, diarrhoea/gastrointestinal issues) and opioid antagonists (e.g. nausea, dry mouth, constipation). There was little consistency in the types of adverse effects experienced by participants receiving mood stabilisers (e.g. tiredness, headaches, concentration difficulties) or atypical antipsychotics (e.g. pneumonia, sedation, increased hypomania). Discontinuation of treatment due to these adverse events was highest for opioid antagonists (10% to 32%), followed by antidepressants (4% to 31%), atypical antipsychotics (14%), and mood stabilisers (13%). Authors' conclusions: This review provides preliminary support for the use of opioid antagonists (naltrexone, nalmefene) and atypical antipsychotics (olanzapine) to produce short-term improvements in gambling symptom severity, although a lack of available evidence precludes a conclusion regarding the degree to which these pharmacological agents can improve other gambling or psychological functioning indices. In contrast, the findings are inconclusive with regard to the effects of mood stabilisers (including anticonvulsants) in the treatment of disordered or problem gambling, and there is limited evidence to support the efficacy of antidepressants. However, these conclusions are based on very low to low certainty evidence characterised by a small number of included studies, high risk of bias, modest pooled sample sizes, imprecise estimates, moderate between-study heterogeneity, and exclusion of participants with psychiatric comorbidities. Moreover, there were insufficient studies to conduct meta-analyses on many outcome measures; to compare efficacy across and within major categories of interventions; to explore dosage effects; or to examine effects beyond post-treatment. These limitations suggest that, despite recommendations related to the administration of opioid antagonists in the treatment of disordered or problem gambling, pharmacological interventions should be administered with caution and with careful consideration of patient needs. A larger and more methodologically rigorous evidence base with longer-term evaluation periods is required before definitive conclusions can be drawn about the effectiveness and durability of pharmacological treatments for disordered or problem gambling.
Gambling disorder affects mental health and wellbeing, and has a strong association with comorbid conditions that include mental health disorders. In the absence of any large‐scale prevalence survey in recent years and the popularity of online gambling, it is important that professionals are aware of the presentation and screening tools used to identify it.
Obsessive-compulsive and related disorders (OCRDs) are a disabling group of psychiatric disorders characterized by urges to perform distressing and time-consuming obsessive-compulsive (excessively repeated, unwanted, stereotyped) acts. The use of the Internet has facilitated a wide range of pathological behaviors conducted online, some of which are similar to those typically observed in OCRDs. Knowledge about these emerging conditions is scant. In cyberchondria, a putative digital form of hypochondriasis, individuals compulsively search online for medical information in order to reduce anxiety related to health concerns but, instead, increased distress or anxiety occurs. In contrast, in information overload, different kinds of information (not only health related) are excessively searched for online. Individuals with cyberhoarding collect digital material to excess, closely resembling hoarding disorder. Repetitive use of social network sites has been described as problematic social network sites use. Compulsive online trading, characterized by compulsive checking and investing in online stock exchange transactions, has also recently been described as a maladaptive digital behavior. This chapter will review and discuss the available knowledge about these problematic online behaviors, focussing on the clinical aspects to better understand their assessment, diagnosis, and treatment.
Naltrexone (NTX) is a well-tolerated drug with a wide safety margin and mechanism of action that affords use across a wide variety of indications in adults and children. By antagonizing the opioid reward system, NTX can modulate behaviors that involve compulsivity or impulsivity, such as substance use, obesity, and eating disorders. Evidence regarding the disposition and efficacy of NTX is mainly derived from adult studies of substance use disorders and considerable variability exists. Developmental changes, plausible disease-specific alterations and genetic polymorphisms in NTX disposition, and pharmacodynamic pathways should be taken into consideration when optimizing the use of NTX in the pediatric population. This review highlights the current state of the evidence and gaps in knowledge regarding NTX to facilitate evidence-based pharmacotherapy of mental health conditions, for which few pharmacologic options exist.
Technical Report
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This review builds on the 2018 NSW gap analysis by reviewing recent Australian and, where relevant, international gambling research to identify areas in which evidence and/or knowledge is minimal or lacking. The findings of the current review will inform the Responsible Gambling Fund’s prioritisation of research projects for their 2020-2021 research plan. The methodology included a rapid literature review of 198 peer-reviewed articles and 17 grey literature reports published between 1 October 2018 and 23 April 2020. Key findings (i) The research on emerging technologies is limited, although there are consistent findings that gaming and gambling are increasingly converging, and of an association between in-game purchases and gambling problems (ii) There is sufficient evidence of the associations between advertising and gambling behaviours to support gambling advertising being a priority for policy and regulation (iii) The evidence base on the effects of prevention and harm reduction intervention is dominated by evaluations of individual-level initiatives, with a paucity of research on supply reduction interventions (iv) There was disagreement in the literature on the definition, conceptualisation and measurement of harm. Further gambling harm measurement tools are needed to support the design and measurement of prevention, harm minimisation and treatment research. (v) Vulnerable groups were consistently found to have lower gambling participation but higher rates of gambling problems.Vulnerable groups were identified as young people, people from culturally and linguistically diverse communities, Aboriginal people, at-risk professions, and groups susceptible to family violence and other co-morbidities.
Le travail présenté dans cette thèse s’attache à démontrer le rôle central joué par le système opioïde dans le développement et le maintien de deux modèles d’addictions comportementales : l’anorexie mentale et l’addiction au sport.Il présente une approche originale, multidisciplinaire et transverse utilisant des techniques modernes et novatrices, avec pour procédé central une imagerie cérébrale TEP/TDM utilisant de la [11C]-diprénorphine comme traceur. Cherchant à obtenir une imagerie en densité de récepteurs opioïdes, une modélisation SRTM a été utilisée. Les images en densité de récepteurs ainsi obtenues ont été exploitées par analyse voxel à voxel sous SPM12. Ces comparaisons statistiques paramétriques ont également intégré plusieurs variables, covariables et paramètres de régressions issus d’analyses complémentaires (tests psychométriques, mesures anthropométriques et analyses biologiques, notamment des dosages d’opioïdes en circulation périphérique mesurés par une technique ELISA).Ces analyses ont démontré la complexité du mécanisme addictif dans ces deux modèles, avec un rôle indirect du système opioïde probablement par modulation du circuit dopaminergique de la boucle méso limbique du circuit de la récompense. Cependant les nombreuses divergences entre ces deux addictions comportementales et les hétérogénéités retrouvées entre les individus montre aussi l’existence d’une sensibilité et de mécanismes variables d’une personne à l’autre, posant la question du phénotypage et de la génétique, et ouvrant le champ à de nouvelles études, avec à terme de possibles répercussions cliniques voire thérapeutiques.
This chapter provides a summary of contemporary research perspectives on both gambling and gaming disorders in women. A discussion of the prevalence of gambling in women is given, as is an overview of gender-specific differences in the kinds of gambling that individuals engage in. A description of the nature of disordered gambling in women is then provided, incorporating a summary of gender differences in the progression of gambling disorder. Comorbidities of gambling disorder in women are described, with a particular focus on barriers to treatment among women. Treatment methods are summarised, incorporating a description of initial advances in pharmacotherapy. The research literature on gaming disorder among women is then treated. Gender differences in both prevalence of gaming and the prevalence of disordered gaming are described. An overview is provided for a nascent literature investigating potential neurobiological explanations for gender differences in gaming disorder. Limitations of the literature are discussed throughout, with a focus placed on how the literature is hampered by a lack of well-defined screening procedures for determining what constitutes disordered gaming.
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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.
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.
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.
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.
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.
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.
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.
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.
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.