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Naltrexone in the Treatment of Broadly Defined Behavioral Addictions: A Review and Meta-Analysis of Randomized Controlled Trials

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Introduction: Broadly defined behavioral addiction is a conceptual framework including behaviors characterized by loss of control and continuation despite significant negative consequences. Broadly defined behavioral addictions share many similarities with substance use disorders. As naltrexone is one of the most studied treatment for substance use disorders, we conducted a meta-analysis of randomized placebo-controlled trials (RCT) assessing the effectiveness of naltrexone in the treatment of broadly defined behavioral addictions. Method: We conducted a literature search and selection, up to January 1, 2017, according to previously set inclusion criteria. The selected trials underwent a quality assessment before data extraction and statistical analysis, which used fixed and random effects models. Standardized mean differences (SMD) were calculated using Hedge's adjusted g. Results: A total of 6 RCTs (n = 356) were included. Of these, 3 assessed naltrexone effectiveness in the treatment of pathological gambling, and 3 tested its benefits in broadly defined behavioral addictions other than pathological gambling (kleptomania, trichotillomania, and impulsive compulsive disorders). The meta-analysis of the whole sample resulted in a statistically significant score improvement under naltrexone versus placebo (fixed effect model: SMD = -0.27, 95% CI [-0.51 to -0.03], z = 2.23; p = 0.025). Conclusion: The results of our meta-analysis suggest a beneficial effect of naltrexone in the treatment of broadly defined behavioral addictions.
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Review
Eur Addict Res 2017;23:204–210
DOI: 10.1159/000480539
Naltrexone in the Treatment of Broadly Defined
Behavioral Addictions: A Review and Meta-Analysis
of Randomized Controlled Trials
Fayçal Mouaffak a Claudio Leite a Sonia Hamzaoui a Amine Benyamina b
Xavier Laqueille c Oussama Kebir c, d
a Unité de Psychiatrie d’Urgence, de Liaison et de Recherche, Pôle 93G04, EPS Ville Evrard, Saint Denis,
and
b Paul Brousse Hospital, Department of Addictology and Psychiatry, Université Paris-Sud, Villejuif ,
c Service d’Addictologie, Moreau de Tours, Centre Hospitalier Sainte-Anne, and
d Laboratory of Pathophysiology
of Psychiatric Diseases, Center for Psychiatry and Neurosciences, University Paris Descartes, Paris , France
ple resulted in a statistically significant score improvement
under naltrexone versus placebo (fixed effect model: SMD =
–0.27, 95% CI [–0.51 to –0.03], z = 2.23; p = 0.025). Conclu-
sion: The results of our meta-analysis suggest a beneficial
effect of naltrexone in the treatment of broadly defined be-
havioral addictions. © 2017 S. Karger AG, Basel
Introduction
Broadly defined behavioral addictions can be defined
“as a process whereby a behavior […] is employed in a
pattern characterized by loss of control and continuation
despite significant negative consequences […]”
[1] . Their
lifetime prevalence rates were estimated at 0.5–6%
[2–4] .
They share many clinical characteristics and neurobio-
logical underpinnings with substance use disorders (i.e.,
tolerance, withdrawal, and relapse)
[5] . While pathologi-
cal gambling was included in the addiction realm for Di-
agnostic and Statistical Manual of Mental Disorders
version 5 (DSM-5), other behaviors such as kleptomania,
hypersexual disorder, trichotillomania, skin picking dis-
order, compulsive buying, and impulse control disorder
in Parkinson disease were not, as research on these disor-
ders was deemed insufficient
[6] .
Keywords
Behavioral addiction · Naltrexone · Opioid antagonist
Abstract
Introduction: Broadly defined behavioral addiction is a con-
ceptual framework including behaviors characterized by
loss of control and continuation despite significant negative
consequences. Broadly defined behavioral addictions share
many similarities with substance use disorders. As naltrex-
one is one of the most studied treatment for substance use
disorders, we conducted a meta-analysis of randomized pla-
cebo-controlled trials (RCT) assessing the effectiveness of
naltrexone in the treatment of broadly defined behavioral
addictions. Method: We conducted a literature search and
selection, up to January 1, 2017, according to previously set
inclusion criteria. The selected trials underwent a quality as-
sessment before data extraction and statistical analysis,
which used fixed and random effects models. Standardized
mean differences (SMD) were calculated using Hedge’s ad-
justed g . Results: A total of 6 RCTs ( n = 356) were included.
Of these, 3 assessed naltrexone effectiveness in the treat-
ment of pathological gambling, and 3 tested its benefits in
broadly defined behavioral addictions other than patholog-
ical gambling (kleptomania, trichotillomania, and impulsive
compulsive disorders). The meta-analysis of the whole sam-
Received: March 9, 2017
Accepted: August 14, 2017
Published online: September 7, 2017
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Dr. Fayçal Mouaffak
Unité de Psychiatrie d’Urgence, de Liaison et de Recherche
Pôle 93G04, EPS Ville Evrard. 5 , rue du Docteur Delafontaine
FR–93200 Saint Denis (France)
E-Mail f.mouaffak @ epsve.fr
© 2017 S. Karger AG, Basel
www.karger.com/ear
Naltrexone in Behavioral Addiction Eur Addict Res 2017;23:204–210
DOI: 10.1159/000480539
205
Beyond phenomenological and neurobiological simi-
larities between broadly defined behavioral addictions
and substance use disorders
[7] , therapeutic response of
these conditions to anti-addiction medications would
constitute a major further proof to characterize them as
addictions. The pharmacological approach to treat sub-
stance use disorders consists in modulating reward mech-
anisms with medications that alter mesolimbic circuits
via glutamatergic, serotonergic, dopaminergic, and opi-
oidergic transmissions
[8–10] . One of the most well stud-
ied medications used for treating behavioral addictions is
naltrexone. Synthesized in 1963, naltrexone is a nonspe-
cific competitive opioid antagonist with high affinity to
μ-opioid receptors in the central nervous system
[11] . It
has been approved by several regulatory bodies for opi-
ates addictions and alcohol use disorder
[12] . Its main ef-
fect appears to be a reduction in the pleasurable effects
from drinking alcohol and, for some, the euphoria and
craving for opiates. Although no medications were ap-
proved for the treatment of broadly defined behavioral
addictions, naltrexone is commonly recommended and
utilized in the treatment of pathological gambling, klep-
tomania, trichotillomania, and other disorders
[12, 13] .
To our knowledge, no formal meta-analysis of the avail-
able data issued from randomized placebo-controlled tri-
als (RCTs) of naltrexone in behavioral addictions has
been conducted. In order to assess the relevance of this
therapeutic option, we conducted a review of the litera-
ture and a meta-analysis of available data from RCTs of
naltrexone in the treatment of behavioral addictions.
Methods
Study Design
The present meta-analysis adheres to the Preferred Reporting
Items for Systematic Reviews and Meta-analyses statement
[14] .
Search Strategy
Our research question was “is naltrexone effective in treating
broadly defined behavioral addictions?” To answer this question, we
meta-analyzed available RCTs. A comprehensive literature search
was performed to find studies, published up to January 1, 2017, on
PubMed Medline, Web of Science, and ClinicalTrials.gov using
combined free text searching with keywords probing. Our key
search terms were “behavioral addictions,” “binge eating disorder,”
“gambling disorder,” “kleptomania,” “trichotillomania,” “hair pull-
ing,” “skin picking,” “excoriation,” “impulsive compulsive,” “hyper-
sexual disorder,” “hypersexuality,” “pathological buying,” “internet
gaming addiction,” “opioid antagonists,” and “naltrexone.” Refer-
ence lists from the resulting publications and reviews were used,
when possible, to identify further relevant publications. We subse-
quently checked articles according to inclusion criteria.
Inclusion and Exclusion Criteria
To be included, studies had to fulfill the following criteria: (1)
a randomized double blind placebo controlled design; (2) partici-
pants diagnosed according to the DSM version III, III-TR, IV, IV-
TR or 5, and/or the ICD-10 as suffering from gambling disorder,
kleptomania, trichotillomania (hair pulling disorder), binge eating
disorder, excoriation (skin picking disorder); (3) efficacy evalua-
tion and outcome reporting rated in a continuous form able to be
synthetized in meta-analysis. Exclusion criteria were as follows: (1)
unavailable or incomplete data; (2) not reported outcome indexes;
(3) noninterventional studies (e.g., case controls, case series, case
controls, and cohorts); (4) nonoriginal studies (e.g., editorials, let-
ters, reviews, and meta-analysis).
Data Extraction
Data extraction was performed separately by 2 authors (C.L.
and O.K.) using a standardized form, collecting information on the
study design, treatment used, characteristics of the sample, num-
ber of participants, and pre- and post-treatment scores on out-
come measures. Authors were contacted, when necessary, for
missing or incomplete data.
Assessment of Study Quality
The Jadad et al.
[15] scale was used to assess the quality of each
study. Criteria of high quality and low quality of included studies
were defined as Jadad score 3 or <3, respectively.
Statistical Analysis
We used fixed effects and random effects models to perform
the statistical analysis
[5] . Standardized mean difference estimates
were calculated using Hedge’s adjusted g . Heterogeneity was eval-
uated using the I
2 statistic and values >50% were considered as
indicative of a large heterogeneity
[6] . Funnel plots were used to
calculate risk of bias and forest plots were generated to show stan-
dardized mean difference with 95% CI for each study. A total of 3
meta-analyses were conducted on total scores. Analyses were per-
formed using MIX 2.0 Professional software for meta-analysis in
Excel, version (2.0.1.5), BiostatXL, 2016
[16, 17] .
Results
Study Inclusion
Our initial search on databases identified 948 studies.
After duplicates removal, 903 studies were retained for
title, abstract, and keywords screening. Of these, 876 were
excluded and 27 left for full text eligibility assessment.
Ultimately, we were left with 6 studies that fully satisfied
the pre-established inclusion criteria (Fig. 1).
Study Characteristics
A total of 356 patients were included in 6 RCTs. The
trial durations ranged from 8 to 20 weeks. Participants
age was 40 ± 11.4 years, and 195 were men (54.75%). The
completers were 281 (79%). Of these, 75 patients discon-
tinued in the 2 arms, 51 in the intervention group and 14
Mouaffak/Leite/Hamzaoui/Benyamina/
Laqueille/Kebir
Eur Addict Res 2017;23:204–210
DOI: 10.1159/000480539
206
in the placebo group. The mean effective dose was report-
ed in only 2 studies
[18, 19] , 100 ± 39.4 and 116.7 ± 44.4
mg/day, respectively. Naltrexone was administered as
needed in only one study
[20] . In the remaining trials,
treatment dose ranged from 50 to 150 mg/day.
Quality Assessment and Risk of Bias
All the selected studies mentioned randomization
and used a computer generated technique. Only one
study did not report its blinding method
[19] . All but
one study
[21] reported on the reasons for withdrawal
in each group. Regarding selective reporting, half of the
studies did not use a protocol registration. According to
Jadad scale
[15] , all the studies were rated as high qual-
ity trials.
Statistical Analysis
Naltrexone for Pathological Gambling
A total of 3 double-blind RCTs were analyzed
[18, 20,
22] , comprising 167 individuals with a diagnosis of path-
ological gambling. A total of 94 individuals were treated
with naltrexone while 73 individuals received a placebo.
Study duration varied from 11 to 20 weeks. Naltrexone
dosage varied from 50 to 150 mg per day. In the 3 studies
included, the primary outcome was the score improve-
ment in Pathological Gambling adaptation of the Yale
Brown obsessive compulsive scale in 2 studies
[20, 22]
and in gambling frequency in last month in the third
study
[18] ).
Naltrexone induced a nonstatistically significant score
improvement than placebo (low heterogeneity: I
2 = 0%,
Q = 1.47, p = 0.48; fixed effects model: standardized mean
differences [SMD] = –0.22, 95% CI [–0.53 to 0.09], z =
1.39, p = 0.16).
Naltrexone for Broadly Defined Behavioral
Addictions Other than Pathological Gambling
A total of 3 double-blind RCTs
[19, 21, 23] were ana-
lyzed, comprising 112 individuals with a diagnosis of
kleptomania, trichotillomania, or impulse control disor-
ders in Parkinson disease. A sum of 53 individuals were
treated with naltrexone and 59 individuals received a pla-
cebo. Study duration was 8 weeks for the 3 RCTs. Naltrex-
one dosage varied from 50 to 150 mg per day. In the 3
Fig. 1. PRISMA flowchart.
Color version available online
Records identified through
database searching
(n = 948)
Additional records identified
through other sources
(n = 0)
Records after duplicates removed
(n = 903)
Records screened on title,
abstract and keywords
(n = 903)
Records excluded
(n = 876)
Full-text articles screened
for eligibility
(n = 27)
Full-text articles excluded
for:
(1) Design reasons: 5
(2) Participant diagnosis
(n = 12)
(3) Unavailable data: 4
Studies included in
metanalysis
(n = 6)
IdentificationScreeningScreeningIncluded
Naltrexone in Behavioral Addiction Eur Addict Res 2017;23:204–210
DOI: 10.1159/000480539
207
studies included, the primary outcome was the score im-
provement on Kleptomania adaptation of the Yale Brown
obsessive compulsive scale for kleptomania
[19] , the
Massachusetts General Hospital Hair Pulling Scale
(MGH-HPS) for trichotillomania
[21], and the Question-
naire for Impulsive Compulsive Disorders in Parkinson’s
Disease-Rating Scale (QUIP-RS)
[23] .
Naltrexone induced a non-statistically significant
score improvement than placebo (low heterogeneity: I
2 =
60%, Q = 5, p = 0.08; fixed effects model: SMD = –0.35,
95% CI [–0.72 to 0.02], z = 1.81, p = 0.07).
Naltrexone for Broadly Defined Behavioral
Addictions
A total of 356 patients suffering from broadly defined
behavioral addictions were randomized to receive either
naltrexone ( n = 198) or placebo ( n = 158; Table1 ). A sum
of 291 participants completed the study, 147 in the nal-
trexone arm and 144 in the placebo arm. Outcome data
were available for 279 patients (147 from the naltrexone
arm and 132 in the placebo group). Study duration varied
from 8 to 20 weeks. Naltrexone dosage varied from 50 to
150 mg per day. The outcome was the score improvement
of the Pathological Gambling adaptation of the Yale
Brown obsessive compulsive scale in 2 studies
[20, 22] ,
gambling frequency in last month
[18] , Kleptomania ad-
aptation of the Yale Brown obsessive compulsive scale for
kleptomania
[19] , MGH-HPS for trichotillomania [21],
and QUIP-RS for impulse control disorders in Parkinson
disease
[23] .
Naltrexone induced a statistically significant score im-
provement than placebo (heterogeneity: I
2 = 25.6%, Q =
6.7, p = 0.24; fixed effects model: SMD = –0.27, 95% CI
[–0.51 to – 0.03], z = 2.23; p = 0.025). Inspection of the
forest plot ( Fig. 2 ) indicates that the main global effect
could be mainly driven by (Grant et al.
[19] ) data. A com-
plementary sensitivity analysis by removing studies one
by one was conducted. The global effect does not reach
significance when data from any of the following 3 studies
were dropped, respectively: Grant et al.
[19] (SMD =
–0.19; p = 0.12), Kovanen et al.
[20] (SMD = 0.25, p =
0.078), and Grant et al.
[22] (SMD = –0.26, p = 0.052).
Table 1. Characteristics of studies included in the meta-analysis
Study Kovanen, 2016 Papay, 2014 Grant, 2014 Toneatto, 2009 Grant, 2009 Grant 2008
Number of patients
baseline
I: 50
C: 51
I: 26
C: 24
I: 25
C: 26
I: 27
C: 25
I: 12
C: 13
I: 58
C: 19
Number of patients
endpoint
I: 32
C: 37
I: 22
C: 23
I: 20
C: 24
I: 26
C: 25
I: 11
C: 12
I: 36
C: 13
Number of drop outs I: 18
C: 14
I: 4
C: 1
I: 5
C: 2
I: 1
C: 0
I: 1
C: 1
I: 22
C: 6
Analysis ITT ITT ITT ITT ITT ITT
Trial duration, weeks 20 8 8 11 8 18
Gender, males, % 68 68 13.7 93 18 40
Age, years mean ± SD 45.9±15.2 61.2±8.5 32.7±9.8 40 34.3±12.1 46.2±9.6
NTX dose, mg 50 Flexible dose from
50 to 100
up to 150 at the 4th week 100±59.4 116±44.4 50, 100 and
150 mg
Diagnostic criteria DSM-IV-TR DSM-IV-TR DSM IV DSM IV DSM IV DSM IV-TR
Diagnosis Pathological
gambling
Impulsive compulsive
disorder
Trichotillomania Adult alcohol abusing
Pathological gambling
Kleptomania Pathological
gambling
Outcome PG-YBOCS QUIP-RS MGH-HPS Gambling frequency
during last month
K-YBOCS PG-YBOCS
JADAD score 5 5 4 5 4 5
C, controls; D, discontinuing; ITT, intention to treat; I, intervention; K-YBOCS, kleptomania adaptation of the Yale Brown obsessive compulsive scale;
MGH-HPS, Massachusetts General Hospital Hair Pulling Scale; NTX, naltrexone; PG-YBOCS, Pathological Gambling adaptation of the Yale Brown obses-
sive compulsive scale; QUIP-RS, Questionnaire for Impulsive Compulsive Disorders in Parkinson’s Disease-Rating Scale.
Mouaffak/Leite/Hamzaoui/Benyamina/
Laqueille/Kebir
Eur Addict Res 2017;23:204–210
DOI: 10.1159/000480539
208
Discussion
Meta-analysis of the 3 controlled trials in pathological
gambling
[18, 20, 22] concluded to a nonstatistically sig-
nificant improvement under naltrexone compared to pla-
cebo. Similarly, the meta-analysis of the 3 RCTs involving
patients suffering from kleptomania, trichotillomania,
and impulse control disorders
[19, 21, 23] resulted in a
nonsignificant improvement under naltrexone. By con-
trast, meta-analysis of the data gathered from the 6 RCTs
suggested that the estimated benefit of naltrexone com-
pared to placebo, although small, was statistically signifi-
cant. Based on data issued from 6 published RCTs, this
meta-analysis is, to our knowledge, the first one suggest-
ing that naltrexone could be a beneficial treatment in
broadly defined behavioral addictions.
Notwithstanding, a number of shortcomings should
be mentioned. First, the heterogeneity of outcome mea-
sures is a limitation. While 3 studies
[19, 21, 22] used
adaptations of the Y-BOCS to assess kleptomania and
pathological gambling, 1 study used a validated measure
of daily frequency and quantity of addictive behavior
(time line follow back)
[18] . The analyzed data from the
2 remaining studies
[21, 23] were extracted from self-
rated questionnaires, the MGH-HPS and QUIP-RS. Sec-
ond, in 2 studies, participants received psychosocial in-
terventions [20] and cognitive behavioral therapy ses-
sions
[18] that may have obscured any differences
attributable to the medication. The absence, in these
studies, of a nontreatment control group precluded the
elimination of nonspecific therapeutic variables. In an
earlier RCT
[24] , not included in our review for lack of
data, the authors tested naltrexone effectiveness against
placebo in pathological gambling. One quarter of the en-
rolled patients (22 on 83) responded to a 1 week placebo
run-in phase. In our meta-analysis, only 2 trials conduct-
ed a 1 week placebo lead-in period, which resulted in the
response of 6 patients (7.2% of the participants) in the
first study
[22] and only one patient in the second trial
[18] . Although disparate, the rate of placebo responders
raises the methodological issue of using longer duration
run-in placebo phase systematically in such trials, where
expected effect size is small and number of patients is
limited. Third, included studies are sparse and of small
sample size; thus, the generalizability of their results is
limited.
Our results are in part similar to the findings of a prior
meta-analysis
[25] assessing the benefit of opiate antago-
nists (3 naltrexone and 2 nalmefene studies) on patho-
logical gambling. The results significantly favored opiate
antagonists ( I 2 = 0%, SMD = 0.18). In our meta-analysis,
the smaller sample size of the included studies probably
Color version available online
Fig. 2. Synthesis forest plot of meta-analysis under fixed effect model.
Weight %
14.39941%
7.16946%
19.48825%
16.59281%
17.17886%
25.17121%
100%
Author (year)
Grant (2008)
Grant (2009)
Toneatto (2009)
Grant (2014)
Papay (2014)
Kovanen (2015)
Synthesis low
0.24471
0.00552
0.84779
0.4908
0.74454
0.15432
0.02574
Messure
(95% CI)
–0.37916
(–1.01797; 0.25965)
–1.28172
(–2.18704; –0.3764)
0.05377
(–0.49533; 0.60288)
–0.20921
(–0.8043; 0.38589)
–0.09723
(–0.68209; 0.48762)
–0.35115
(–0.83431; 0.13201)
–0.27581
(–0.51822; –0.03341)
210–1–2–3
Favours NTX
HG
p value
Naltrexone in Behavioral Addiction Eur Addict Res 2017;23:204–210
DOI: 10.1159/000480539
209
precluded the detection of such a significant effect on
pathological gambling.
Since its approval by the Food and Drug Administra-
tion in 1995, the recommended naltrexone dose in alco-
hol dependence is 50 mg per day
[12] . However, clinical
data suggest that naltrexone high doses (up to 150 mg per
day) are of greater effectiveness in broadly defined behav-
ioral addictions
[26] . In our review, although the major-
ity of participants had received doses higher than 50 mg
per day, no severe adverse effects have been reported. Na-
ltrexone has low affinity at κ receptors in the brain and
spinal cord and little to no activity at δ receptors in the
spinal cord and peripheral nervous system
[27] . Actually,
pharmacological studies, established that 95% of cerebral
μ receptors are occupied after an oral dose of 50 mg while
only partial inhibition is produced on δ receptors
[28] . As
higher doses than 50 mg per day are needed to produce
inhibition of δ receptors
[28] , we could speculate that
these receptors can play a critical role in naltrexone effect
in broadly defined behavioral addictions treatment.
Our meta-analysis beyond suggesting a possible ben-
efit of naltrexone in broadly defined behavioral addic-
tions adds to the arguments supporting the idea that such
behaviors should be considered as addictions. Neurocog-
nitive research has yielded valuable data on the role of
impulsivity, a trait that has been linked to both substance
use disorders and broadly defined behavioral addictions;
actually, the latter are in part referred to as impulsive
compulsive disorder in DSM-5. The impulsivity that
seems to characterize addiction may be caused by disrup-
tions within the opioid system. Mouse μ receptor knock-
out models show remarkably decreased motor impulsiv-
ity
[29] and higher μ receptor availability has been associ-
ated with greater impulsivity
[30] . Hence, naltrexone, as
μ receptor antagonist, through reducing impulsivity may
be effective across a rather broad spectrum of addictions
involving both broadly defined behavioral addictions and
substance use disorders.
Although a growing body of evidence suggests its rela-
tive safety and effectiveness, naltrexone remains an unde-
rutilized treatment option
[12] . Given the high morbidity
associated with addiction and the lack of alternate thera-
peutic strategies
[12] , further studies with longer dura-
tion, higher doses, and more methodological accuracy
should be conducted in order to confirm or infirm the
relevance of naltrexone in the treatment of broadly de-
fined behavioral addictions. Analyzing studies using na-
lmefene, another recently marketed μ antagonist but less-
er investigated than naltrexone could also improve our
understanding of the role of the opioid neurotransmis-
sion in the pathophysiology of addictive disorders.
Disclosure Statement
All authors have no conflicts of interest.
Authors Contributors
All the authors were involved in the study design, had full ac-
cess to the survey data and analyses, and interpreted the data, crit-
ically reviewed the manuscript, and had full control, including fi-
nal responsibility for the decision to submit the paper for publica-
tion.
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... As a μ-receptor antagonist naltrexone reduces impulsive behaviors. Thus, naltrexone may be effective across a rather broad spectrum of addictions involving both broadly defined behavioral addictions and substance use disorders (Mouaffak et al. 2017). Based on data from 6 published RCTs on different behavioral addictions, a metaanalysis by Mouaffak et al. (2017) concluded that naltrexone could be a beneficial treatment for broadly defined behavioral addictions. ...
... Thus, naltrexone may be effective across a rather broad spectrum of addictions involving both broadly defined behavioral addictions and substance use disorders (Mouaffak et al. 2017). Based on data from 6 published RCTs on different behavioral addictions, a metaanalysis by Mouaffak et al. (2017) concluded that naltrexone could be a beneficial treatment for broadly defined behavioral addictions. Several case reports and case series have provided evidence that naltrexone could be helpful in patients with CSBD as well (Bostwick & Buchi 2008, Camacho et al. 2018, Raymond et al. 2002, Ryback 2004. ...
Chapter
This chapter provides an overview of the different pharmacological therapeutic approaches in CSBD. It focuses on the following key aspects of an indication: to enhance sexual self-control, reduce sexual drive, treat comorbid psychiatric disorders, and treat a combination of paraphilic disorders with CSBD. The proposed medications include naltrexone, selective serotonin reuptake inhibitors (SSRI), cyproterone acetate, medroxyprogesteroneacetat, and GnRH agonists like leuprolide. It becomes clear that especially in the initial therapy phase as well as in the case of a risk for sexual offending behaviour, medication is an important addition to psychotherapy in patients with CSBD. The chapter concludes with a proposal for a treatment algorithm based on the severity of CSBD and comorbidity. 3
... Potently inhibit the reuptake of 5-HT Effective as a monotherapy or as an augmentation agent in the treatment of impulsive (PG, KM, TTM, IED and pyromania), addiction and compulsive disorders [35][36][37][38][39] Listed above Mood stabilisers e.g., olanzapine, carbamazepine Defined above Naltrexone Non-specific competitive opioid antagonist with highest affinity for the mu-opioid receptors in the CNS [39] Nausea, vomiting, abdominal pain, decreased appetite, dizziness, lethargy, headaches and sleep disorders [40] Personality disorders Antidepressants (SSRIs, SNRIs) Defined above Shown efficacy in the treatment of BPD [41,42] Listed above Quetiapine Naltrexone ...
... Potently inhibit the reuptake of 5-HT Effective as a monotherapy or as an augmentation agent in the treatment of impulsive (PG, KM, TTM, IED and pyromania), addiction and compulsive disorders [35][36][37][38][39] Listed above Mood stabilisers e.g., olanzapine, carbamazepine Defined above Naltrexone Non-specific competitive opioid antagonist with highest affinity for the mu-opioid receptors in the CNS [39] Nausea, vomiting, abdominal pain, decreased appetite, dizziness, lethargy, headaches and sleep disorders [40] Personality disorders Antidepressants (SSRIs, SNRIs) Defined above Shown efficacy in the treatment of BPD [41,42] Listed above Quetiapine Naltrexone ...
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Mushrooms have been used as traditional medicine for millennia, fungi are the main natural source of psychedelic compounds. There is now increasing interest in using fungal active compounds such as psychedelics for alleviating symptoms of mental health disorders including major depressive disorder, anxiety, and addiction. The anxiolytic, antidepressant and anti-addictive effect of these compounds has raised awareness stimulating neuropharmacological investigations. Micro-dosing or acute dosing with psychedelics including Lysergic acid diethylamide (LSD )and psilocybin may offer patients treatment options which are unmet by current therapeutic options. Studies suggest that either dosing regimen produces a rapid and long-lasting effect on the patient post administration with a good safety profile. Psychedelics can also modulate immune systems including pro-inflammatory cytokines suggesting a potential in the treatment of auto-immune and other chronic pain conditions. This literature review aims to explore recent evidence relating to the application of fungal bioactives in treating chronic mental health and chronic pain morbidities.
... Thus, given the evidence for an underlying structure to psychopathology, a criterion for any candidate behavioural addiction is that it should be able to plausibly reside within that structure alongside established addictions (Taxonomic Plausibility, Criterion 4; Achenbach & Edelbrock, 1978;Forbes et al., 2021;Krueger, 1999;Meehl, 1986). Obsessive-compulsive disorder and trichotillomania are not addictions to handwashing and hair-pulling, respectively, despite similarities to addictive disorders in certain clinical features and neurobiological correlates (Grassi & Pallanti, 2017;Mouaffak et al., 2017). There are important differences in clinical course, prognosis, and response to treatment suggesting: 1) a different underlying cause, and; 2) that grouping them with addictions would be of little clinical utility -in fact, it may reduce utility (Farhat et al., 2020;Grant, Odlaug, Schreiber, & Kim, 2014;Kendell & Jablensky, 2003;Meehl, 1986;Stein et al., 2010Stein et al., , 2019. ...
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When does repeated behaviour constitute behavioural addiction? There has been considerable debate about non-substance-related addictions and how to determine when impaired control over a behaviour is addiction. There are public health benefits to identifying new behavioural addictions if intervention can improve outcomes. However, criteria for establishing new behavioural addictions must guard against diagnostic inflation and the pathologizing of normal problems of living. Criteria should include clinical relevance (Criterion 1), alignment with addiction phenomenology (Criterion 2) and theory (Criterion 3), and taxonomic plausibility (Criterion 4). Against such criteria, evidence does not yet support classification of pornography-use and buying-shopping disorders as addictions.
... [150][151][152] For example, molecules already tested for substance use disorders may also be used for BAs. This is the case for opioid antagonists such as naltrexone, which was tested in patients with compulsive sexual behavior 22 or GbD, 153,154 or nalmefene, which was tested in patients with GbD. 155 Moreover, a transversal approach would permit clinicians to not surcharge for multiple therapies and improve the impact of therapies because of co-occurrences. ...
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Introduction: Only two behavioral addictions (BAs) are currently recognized in international classifications (gambling disorder: GbD; gaming disorder: GmD), while some of them await further investigation (food addiction: FA; sexual addiction: SA). Neurocognitive functioning is considered a risk factor for BAs. Research is quite abundant for GbD and highlights specific deficits in several cognitive functions. Nevertheless, grey areas still exist. The aim of this research programme is to investigate the neurocognitive profiles of patients presenting with various BAs and to establish parallels between different forms of BA to achieve a common addiction concept. Methods and analysis: This research program is composed of two studies sharing the same methodology but focusing on different samples: the BANCO study aims to include 30 individuals with a GbD, whereas the BANCO2 study aims to include 30 individuals with a GmD, 30 with a SA, and 30 with a FA. Moreover, for each BA group, 30 healthy controls will be recruited, matched by sex, age and education level. Several cognitive tasks will be completed by participants. Cue reactivity and physiological responses, as well as clinical data regarding addiction characteristics and personality, will also be investigated. A composite score based on the cognitive tasks will be computed using principal component analysis (PCA). Overall cognitive performance and detailed performance on the different cognitive tasks will be compared between individuals with BAs and their matched healthy controls using linear models with random effects. Comparisons will also be made between BA groups to investigate specific alterations associated with each disorder. Discussion: The results of this research programme will impact both research and clinical areas by (i) providing new knowledge for discussions regarding the inclusion of BAs under the spectrum of addictive disorders; (ii) improving understanding of addiction mechanisms in general; (iii) providing clarity in the grey areas in neurocognitive research on BAs and improving the understanding of less studied BAs, (iv) guiding clinicians to propose therapeutic alternatives and complementary programmes. Trial registration: BANCO study (ClinicalTrials.gov NCT03202290); BANCO2 study (ClinicalTrials.gov NCT03967418).
... This clinical picture was accompanied of withdrawal symptoms, including negative mood and increased stress reactivity, and an impairment of their personal, professional, and social life. In contrast to SUD, no approved medication for the treatment of behavioral addictions is available (Mouaffak et al., 2017). However, since underlying neural processes as well as clinical symptoms are found to be similar in BA and SUD (Grant et al., 2010), we sought that non-invasive neuromodulation intervention might be a promising candidate for the treatment of behavioral addictions as well. ...
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Background Several behaviors, besides consumption of psychoactive substances, produce short-term reward that may lead to persistent aberrant behavior despite adverse consequences. Growing evidence suggests that these behaviors warrant consideration as nonsubstance or “behavioral” addictions, such as pathological gambling, internet gaming disorder and internet addiction. Case presentation Here, we report two cases of behavioral addictions (BA), compulsive sexual behavior disorder for online porn use and internet gaming disorder. A 57-years-old male referred a loss of control over his online pornography use, started 15 years before, while a 21-years-old male university student reported an excessive online gaming activity undermining his academic productivity and social life. Both patients underwent a high-frequency repetitive transcranial magnetic stimulation (rTMS) protocol over the left dorsolateral prefrontal cortex (l-DLPFC) in a multidisciplinary therapeutic setting. A decrease of addictive symptoms and an improvement of executive control were observed in both cases. Discussion Starting from these clinical observations, we provide a systematic review of the literature suggesting that BAs share similar neurobiological mechanisms to those underlying substance use disorders (SUD). Moreover, we discuss whether neurocircuit-based interventions, such as rTMS, might represent a potential effective treatment for BAs.
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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.
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Today there are no international standards for the treatment of non-chemical (behavioral) addiction (NA). This is largely due to the vagueness of their existence as nosological units and, as a consequence, their place in international classifications. This article discusses the forms of NA that are or will be included in DSM-V and ICD-11. It has been shown that NA research has sparked discussions about the spectrum of addictive disorders, expands the multidisciplinary understanding of the etiology and pathogenesis of addictive disorders, and promotes the study of new forms and expansion of therapeutic approaches. The criticism of the addictive spectrum concept is analyzed. The modern approaches of non-drug and pharmacological therapy of different forms of NA are presented. The following conclusions are drawn. The existence of NA is confirmed by the inclusion of a part of them in the International Classifications of Diseases. NA have high comorbidity with other mental disorders, in respect of which pharmacotherapy and psychotherapy are not in doubt. Taking into account the general neurobiological mechanisms of the formation of addictive disorders, the possible pharmacotherapy of non-chemical addictions, officially recognized in the ICD and DSM, should proceed from the currently available approaches to the therapy of substance use disorders. Treatment of non-chemical addictions that are not included in the International Classifications can only be carried out within the framework of therapy for confirmed comorbid mental disorders. In its absence, psychological correction seems to be possible. There is an obvious need to continue researching the problem of non-chemical addictions to expand new approaches to their therapy and psychological correction.
Chapter
Internet addiction has gradually turned a medium of gaming and other leisure activities shifting from its original intention to fasten the communication and help in the researches. The excessive usage of internet and nature of its usage has been found to be similar with psycho-addictive substance addiction with similar neurobiological basis. Inclusion of gambling disorder into DSM 5 further strengthens the emerging concept of behavioral addiction. Various worldwide researches also support the upsurge of such problem. The clinical presentation and management options are mostly based on the behavioral principles learned from the substance abuse problems. However, large-scale randomized trails and epidemiological studies are definitely needed to understand this twenty-first century problem.
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Psychodermatological (PD) conditions encountered in dermatologic practice include primary psychiatric conditions such as delusions of parasitosis or secondary psychiatric conditions such as anxiety and depression due to dermatologic disease. The psychotropics include antipsychotic agents, anti-anxiety agents, antidepressants, and miscellaneous drugs such as anti convulsants. Anti psychotics are further divided into first-generation and second-generation drugs. Currently, second-generation drugs e.g., risperidone are preferred over first-generation drugs e.g., pimozide in delusional infestation owing to the side effect profile of the latter. Anti-anxiety agents include benzodiazepines used in acute anxiety and buspirone in chronic anxiety disorders. They are frequently prescribed along with antidepressants. Although dependence and necessity of tapering is a problem with benzodiazepines, delayed onset of action is a feature of buspirone. The commonly used antidepressants in dermatology include selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), selective serotonin norepinephrine reuptake inhibitors (venlafaxine, desvenlefaxine, and duloxetine), norepinephrine dopamine reuptake inhibitors (bupropion), tricyclic antidepressants (doxepin, amitriptyline, imipramine, and clomipramine), and tetracyclic antidepressants (mirtazapine). Miscellaneous drugs include anticonvulsants such as gabapentin and pregabalin, naltrexone, and N-acetyl cysteine. The principles of PD treatment are first establish the psychiatric diagnosis, followed by initiating drug treatment. The choice of drugs is dependent on multiple factors such as side-effect profile, drug interactions, and co-morbid conditions. Usually, drugs are started at a low dose and gradually increased. A literature search was done in Pubmed, Google Scholar, and Medline databases, and articles on treatment were analyzed.
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Introduction: Naltrexone (NTX), a mu-opioid receptor antagonist, has been approved for the treatment of alcoholism and opioid dependence. More recently, however, NTX and a related drug, nalmefene (NMF), have also shown positive results for the treatment of gambling disorders. Areas covered: In this study, we reviewed the trials testing the effect of opioid antagonists (OA) in gambling disorders and in other "broadly" defined behavioral addictions, including selected DSM-5 disruptive, impulse-control, and conduct disorders, obsessive-compulsive and related disorders, and other conditions not currently recognized by official classification schemes. We found six randomized controlled trials (RCTs) of OA in gambling disorder, two RCTs of OA in trichotillomania (hair pulling disorder), two RCTs of OA in binge eating disorder, and one RCT of OA for kleptomania. We also reviewed case reports on hypersexual disorder, compulsive buying and skin picking disorders. Expert opinion: The reviewed data supported the use of OA, namely NTX and NMF, in gambling disorder (both) and kleptomania (NTX). We did not find enough evidence to support the use of NTX or NMF in trichotillomania (hair pulling disorder), excoriation (skin-picking) disorder, compulsive buying disorder, hypersexual disorder, or binge eating disorder.
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Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. 14 PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may play an important role in the pathophysiology of addictions.Neuropsychopharmacology accepted article preview online, 10 November 2015. doi:10.1038/npp.2015.340.
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While considerable efforts have been made to understand the neurobiological basis of substance addiction, the potentially “addictive” qualities of repetitive behaviors, and whether such behaviors constitute “behavioral addictions,” is relatively neglected. It has been suggested that some conditions, such as gambling disorder, compulsive stealing, compulsive buying, compulsive sexual behavior, and problem Internet use, have phenomenological and neurobiological parallels with substance use disorders. This review considers how the issue of “behavioral addictions” has been handled by latest revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD), leading to somewhat divergent approaches. We also consider key areas for future research in order to address optimal diagnostic classification and treatments for such repetitive, debilitating behaviors.
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Behavioral addictions, such as pathological gambling, kleptomania, pyromania, compulsive buying, and compulsive sexual behavior, represent significant public health concerns and are associated with high rates of psychiatric comorbidity and mortality. Although research into the biology of these behaviors is still in the early stages, recent advances in the understanding of motivation, reward, and addiction have provided insight into the possible pathophysiology of these disorders. Biochemical, functional neuroimaging, genetic studies, and treatment research have suggested a strong neurobiological link between behavioral addictions and substance use disorders. Given the substantial co-occurrence of these groups of disorders, improved understanding of their relationship has important implications not only for further understanding the neurobiology of both categories of disorders but also for improving prevention and treatment strategies.
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Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement-a reporting guideline published in 1999-there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (www.prisma-statement.org) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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Objective: Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD. Methods: Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1:1), double-blind, placebo-controlled study of naltrexone 50-100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score. Results: Forty-five patients (90%) completed the study. The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8% (95% confidence interval [CI] -8.7% to 44.2%). While this difference was not significant (odds ratio=1.6, 95% CI 0.5-5.2, Wald χ2 [df]=0.5 [1], p=0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model=-7.37, F[df]=4.3 [1, 49], p=0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo. Conclusions: Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD. Classification of evidence: This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates.
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Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were randomized to naltrexone or placebo in an 8-week, double-blind trial. Subjects were assessed with measures of TTM severity and selected cognitive tasks. Naltrexone failed to demonstrate significantly greater reductions in hair pulling compared to placebo. Cognitive flexibility, however, significantly improved with naltrexone (P = 0.026). Subjects taking naltrexone with a family history of addiction showed a greater numerical reduction in the urges to pull, although it was not statistically significant. Future studies will have to examine whether pharmacological modulation of the opiate system may provide promise in controlling pulling behavior in a subgroup of individuals with TTM.