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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. George’s 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 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.
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 significant impairment or
distress (American Psychiatric Association, 2013). Sufferers
tend to become increasingly involved in terms of time and
financial commitment, continuing to gamble regardless of
the impact on their personal, social, and financial 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, financial matters, and interpersonal relation-
ships (Grant & Kim, 2001). There is a significant 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 identified 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 (45–54 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. 827–833 (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 significant 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 efficacy 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 resort”once psychological interventions
have failed. Grant et al. (2014) reviewed 18 randomized
control trials across five 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 efficacy 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. Significant 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 specifically looked at the efficacy of daily
naltrexone in PG (Kim & Grant 2001;Kim, Grant, Adson,
& Shin, 2001;Grant, Kim, & Hartman, 2008), finding
significant 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), finding more mixed results. For
completeness, we reviewed studies of another opioid antago-
nist, nalmefene. Grant et al. (2006) showed significant 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 findings 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 files 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 confirmed
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 reflective question-
naire on the patient’s 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 patient’s general practitioner.
Of the 14 cases, there were 10 for whom sufficient
follow-up existed to enable a meaningful analysis of the
efficacy 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 reflective questionnaire. There were a further two cases
for whom answers to the reflective 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. 827–833 (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 first
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 disfigurement
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
Crohn’s 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
first few
days
None
6 37, M From
inpatient
unit
25 £1,000,000 14 None reported Obsessive
compulsive
traits
None reported None
reported
No significant family
history, having
young children
Under
investigation
for missing
stock at
work
Abstinence 28 5 Stomach
pains,
dizziness,
nausea,
and
headaches
for the first
few days
None
(Continued)
Journal of Behavioral Addictions 7(3), pp. 827–833 (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-
deficit
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 first
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
Significant
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. 827–833 (2018)
Ward et al.
significant 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-specific 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 deficit 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 significant 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
first 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
risk”of 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 risk”of 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 reflective 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 difficult 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 specified 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 difficulties.
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 efficacious 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 efficacy
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 efficacy 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 specificefficacy in PG
would be worthwhile.
We found that alcohol consumption seemed to increase
the treatment resistance of a patient’s PG, based upon the
relapses of the heavy drinkers in the sample set. Baron and
Dickerson (1999) found that alcohol consumption signifi-
cantly increases impairment in control of gambling
Journal of Behavioral Addictions 7(3), pp. 827–833 (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 resort”treatment 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 benefits 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.
Authors’contribution: 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.
Conflict 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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