Interventions for comorbid problem gambling and psychiatric disorders: Advancing a developing field of research

Addictive Behaviors 58 (2016) 21–30

Contents lists available at ScienceDirect

Addictive Behaviors journal homepage: www.elsevier.com/locate/addictbeh

Interventions for comorbid problem gambling and psychiatric disorders: Advancing a developing field of research N.A. Dowling a,b,c,⁎, S.S. Merkouris a, F.K. Lorains a a b c

School of Psychology, Deakin University, Australia Melbourne Graduate School of Education, University of Melbourne, Australia Centre for Gambling Research, Australian National University, Australia

H I G H L I G H T S • • • • •

Few treatment recommendations for gamblers with psychiatric comorbidity are available. We highlighted gaps in the available evidence base using two systematic searches. Research exploring the effect of sequenced interventions is required. Research aimed at identifying moderators of change would enhance treatment efficacy. Studies exploring efficacy of interventions matched to client comorbidity are needed.

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Article history: Received 19 September 2015 Received in revised form 4 February 2016 Accepted 7 February 2016 Available online 10 February 2016 Keywords: Problem gambling Intervention Treatment Psychological Pharmacological Gambling disorder

a b s t r a c t Despite significant psychiatric comorbidity in problem gambling, there is little evidence on which to base treatment recommendations for subpopulations of problem gamblers with comorbid psychiatric disorders. This minireview draws on two separate systematic searches to identify possible interventions for comorbid problem gambling and psychiatric disorders, highlight the gaps in the currently available evidence base, and stimulate further research in this area. In this mini-review, only 21 studies that have conducted post-hoc analyses to explore the influence of psychiatric disorders or problem gambling subtypes on gambling outcomes from different types of treatment were identified. The findings of these studies suggest that most gambling treatments are not contraindicated by psychiatric disorders. Moreover, only 6 randomized studies comparing the efficacy of interventions targeted towards specific comorbidity subgroups with a control/comparison group were identified. The results of these studies provide preliminary evidence for modified dialectical behavior therapy for comorbid substance use, the addition of naltrexone to cognitive-behavioral therapy (CBT) for comorbid alcohol use problems, and the addition of N-acetylcysteine to tobacco support programs and imaginal desensitisation/motivational interviewing for comorbid nicotine dependence. They also suggest that lithium for comorbid bipolar disorder, escitalopram for comorbid anxiety disorders, and the addition of CBT to standard drug treatment for comorbid schizophrenia may be effective. Future research evaluating interventions sequenced according to disorder severity or the functional relationship between the gambling behavior and comorbid symptomatology, identifying psychiatric disorders as moderators of the efficacy of problem gambling interventions, and evaluating interventions matched to client comorbidity could advance this immature field of study. © 2016 Elsevier Ltd. All rights reserved.

Contents 1. 2. 3.

Introduction . . . . . . . . . . . . . . Method . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . 3.1. Alcohol and substance use disorders 3.2. Mood disorders . . . . . . . . .

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⁎ Corresponding author at: School of Psychology, Faculty of Health, Deakin University, Building W, 221 Burwood Highway, Burwood, VIC 3125, Australia. E-mail address: [email protected] (N.A. Dowling).

http://dx.doi.org/10.1016/j.addbeh.2016.02.012 0306-4603/© 2016 Elsevier Ltd. All rights reserved.

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3.3. Anxiety disorders . . . . . . . . . . . . . . . 3.4. Attention deficit hyperactivity disorder (ADHD) . 3.5. Impulse control disorders . . . . . . . . . . . 3.6. Schizophrenia . . . . . . . . . . . . . . . . 3.7. Eating disorders . . . . . . . . . . . . . . . 3.8. Personality disorders . . . . . . . . . . . . . 3.9. Problem gambling subtypes . . . . . . . . . . 4. Discussion . . . . . . . . . . . . . . . . . . . . . Role of funding sources . . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . Appendix A. Supplementary data . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction The evidence base for problem gambling interventions supports the use of cognitive and/or behavioral therapies (CBT), motivational interviewing (MI), and opioid antagonists (Cowlishaw et al., 2012; Thomas et al., 2011). The treatment of problem gambling is, however, complicated by substantial comorbidity with other psychiatric disorders (Dowling et al., 2015a; Dowling et al., 2015b; Lorains, Cowlishaw, & Thomas, 2011). Moreover, there is growing empirical support for the presence of subtypes of problem gamblers that may respond preferentially to certain treatments (Milosevic & Ledgerwood, 2010; Rodda, Lubman, Iyer, Gao, & Dowling, 2015; Suomi, Dowling, & Jackson, 2014), as proposed by recent theoretical typologies of problem gambling, such as the pathways model proposed by Blaszczynski and Nower (2002) and the clinical typology proposed by Dannon, Lowengrub, Gonopolski, Musin, & Kotler (2006). Psychiatric comorbidity in problem gambling is associated with more complex clinical presentations (Pietrzak & Petry, 2005; Stinchfield, Kushner, & Winters, 2005) and may introduce a source of variance that interacts with delivered interventions (Toneatto & Millar, 2004). The problem gambling treatment outcome literature has, however, generally ignored psychiatric comorbidities, excluded individuals with comorbidities, or employed small samples that preclude the detection of comorbidity subgroup differences in treatment responses. At present, most evidence regarding the identification of particular treatment strategies best suited to particular comorbid psychiatric disorders of problem gamblers is derived from post hoc analyses of treatment delivered to heterogeneous groups of problem gamblers. The existence of problem gambling sub-populations based on psychiatric comorbidity may, however, also have implications for individually tailored intervention approaches (Winters & Kushner, 2003) that could maximize treatment response, enhance client satisfaction, reduce attrition, and lower treatment costs (Grant, Williams, & Kim, 2006). In this mini-review, we aim to highlight the gaps in the literature that preclude the identification of treatment recommendations for sub-populations of problem gamblers with comorbid psychiatric disorders. We identify: 1) studies examining the influence of comorbid psychiatric disorders and problem gambling subtypes on gambling treatment outcomes, and 2) randomized trials evaluating the efficacy of intervention approaches for problem gamblers with specific psychiatric comorbidities. We conclude with a discussion of the gaps in the current evidence base and suggestions for further research to advance this developing field of research. 2. Method This review drew upon two separate systematic literature searches. The first search was designed to explore the influence of client characteristics on gambling treatment outcomes; but it did not emphasise the types of treatment that produced these outcomes (Merkouris,

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Thomas, Browning, & Dowling, submitted for publication). The second search was designed to explore the efficacy of pharmacological interventions for problem gambling; but it did not emphasise the efficacy of psychological or pharmacological treatments for problem gamblers with comorbid psychiatric disorders (Dowling et al., in preparation). Studies from the first search were considered eligible for this minireview if they examined the influence of pre-treatment psychiatric disorders or problem gambling subtypes on gambling treatment outcomes, while studies from the second search were considered eligible if they compared the efficacy of an intervention for problem gamblers with a comorbid psychiatric disorder with a control/comparison group (see Fig. 1 and Supplementary Data). Included were 21 studies from the first search (Table 1) and 6 studies from the second search (Table 2). 3. Results 3.1. Alcohol and substance use disorders Treatment-seeking problem gamblers display high rates of alcohol use (21.2%) and substance (non-alcohol) use (7.0%) disorders, specifically alcohol abuse (18.2%), alcohol dependence (15.2%), substance abuse (6.6%), substance dependence (4.2%), and cannabis use disorder (11.5%) (Dowling et al., 2015b). Problem gamblers with comorbid substance use, even cigarette smoking, generally have higher gambling severity, problem gambling durations, gambling frequency and expenditures, craving, psychiatric symptoms, other psychosocial difficulties, and perceived control difficulties than those without these comorbid disorders (Feigelman, Wallisch, & Lesieur, 1998; Kausch, 2003; Ladd & Petry, 2003; Petry & Oncken, 2002; Stinchfield et al., 2005; Toneatto et al., 2002). Retrospective age of onset data suggests that alcohol and substance use disorders most often begin at an earlier age than problem gambling (Kessler et al., 2008). This data suggests that although there are significant time-lagged predictive associations for alcohol and substance use disorders predicting subsequent onset of problem gamblers, there are stronger associations for problem gambling predicting subsequent onset of alcohol and substance use disorders (Kessler et al., 2008). Longitudinal research confirms that problem gambling predicts the subsequent onset of many alcohol and substance use disorders (Chou & Afifi, 2011), but that alcohol and substance use problems are also prospectively associated with the development of problem gambling (Dowling, Merkouris, et al., 2015). Eleven articles exploring whether alcohol and substance use disorders influence treatment efficacy were identified. There is some evidence that these disorders are associated with poorer gambling outcomes following CBT (Milton et al., 2002), imaginal desensitisation plus MI (Grant et al., 2011), and internet-based CBT self-help (Carlbring et al., 2012). There is, however, more evidence that these disorders are unrelated to gambling outcomes following CBT (Dowling, 2009; Manning et al., 2014; Milton et al., 2002; Toneatto et al., 2002), behavioral treatments (Blaszczynski et al., 1991a; Smith, Battersby, et al.,

N.A. Dowling et al. / Addictive Behaviors 58 (2016) 21–30

23

Fig. 1. Inclusion/exclusion criteria for systematic searches.

2011), MI (Toneatto et al., 2002), internet-based CBT self-help (Carlbring et al., 2012), 12-step therapy (Toneatto et al., 2002), solution-focused therapy (Toneatto et al., 2002), paroxetine (Grant et al., 2003), lithium or valproate (Pallanti et al., 2002), or naltrexone or nalmefene (Grant et al., 2008), suggesting that these may be effective treatments for problem gamblers with comorbid alcohol and substance use disorders.

The second search identified three randomized trials exploring the efficacy of interventions specifically evaluated for problem gamblers with comorbid alcohol and substance use disorders. Korman et al. (2008) evaluated a 14-week integrated treatment for problem gambling and comorbid anger and substance use (modified dialectical behavior therapy addressing anger and addiction problems) compared to a specialised treatment-as-usual. The integrated treatment reduced

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Table 1 Characteristics of included studies from first systematic search. Study

Sample size

Country

Treatment type

Psychiatric comorbidity

Timing of treatment outcome assessment

Gambling outcome(s)

Black et al. (2007)

8

USA

Bupropion

ADHD (ADHD Rating Scale)

Post-treatment

Breen, Kruedelbach, and Walker (2001)

56

USA

Depression (BDI)

Post-treatment

Blaszczynski, McConaghy, and Frankova (1991a)a

18

Australia

Individual and group inpatient CBT and standard didactic component Behavioral treatment (imaginal desensitization, brief or prolonged in vivo exposure, aversive therapy, or relaxation training)

Gambling symptom severity (YBOCS-PG total score) Gambling symptom severity (GABS)

Alcohol use (weekly number of standard drinks) Anxiety (STAI)

2 to 9 years following treatment

Blaszczynski, McConaghy, and Frankova (1991b)a

63

Australia

Behavioral treatment (imaginal desensitization, brief or prolonged in vivo exposure, aversive therapy, or relaxation training)

Anxiety (STAI)

2 to 9 years following treatment

Carlbring, Degerman, Jonsson, and Andersson (2012)

196–218 Sweden

Internet delivered self-help CBT

Post-treatment and 36 months follow-up

Dowling (2009)

57–62

Individual CBT

Alcohol use (1 item AUDIT measuring number of standard drinks during typical drinking day); Alcohol or substance use problem (MMPI-II) Depression (BDI) Anxiety (STAI)

Australia

Post-treatment and 6 months follow-up

Gambling frequency (no gambling episodes during the previous month and for the predominant post-treatment period versus abstinence with intermittent relapse episodes) Abstinence (no episodes of gambling in the month immediately preceding interview and for the predominant portion of the post-treatment period) vs controlled gambling (gambling in the absence of both a subjective sense of impaired control and adverse financial consequences) vs uncontrolled gambling Treatment response (NODS score of 0 and no gambling days in previous month) Abstinence/controlled gambling (spending no more than AUD$20 per week and spending no more than intended at any one session in previous month and inter-evaluation period) Treatment response (a 35% or greater reduction in PG-YBOCS total score at end point compared with baseline and a score of 1 or 2 on the CGI improvement scale [“very much improved” or “much improved”]) Treatment response (a 35% reduction in PG-YBOCS total score in previous month) (PG-YBOCS)

Grant, Chamberlain, Odlaug, Potenza, and Kim (2010)

29

USA

Memantine

Depression (HAM-D) Anxiety (HAM-A)

Post-treatment

Grant, Donahue, Odlaug, and Kim (2011)

35

USA

Imaginal desensitisation plus motivational interviewing

6 months follow-up

Grant, Kim, Hollander, and Potenza (2008)

214

USA

Post-treatment

Treatment response (a 35% or greater reduction in PG-YBOCS total score for at least 1 month by study endpoint)

Grant, Kim, and Odlaug (2007)

27

USA

Opioid antagonists (naltrexone or nalmefene: collapsed treatment groups after establishing no group differences) N-acetyl cysteine

Nicotine use Mood disorders (SCID) Anxiety disorders (SCID) Impulse control disorders (SCID) Eating disorders (SCID) Nicotine use Depression (HAM-D) Anxiety (HAM-A)

Depression (HAM-D) Anxiety (HAM-A)

Post-treatment

Grant et al. (2003)

34

USA

Paroxetine

Nicotine use

Post-treatment

Guo et al. (2014)a

45–57

Singapore Individual CBT

Depression (HADS) Anxiety (HADS)

Jimenez-Murcia et al. (2007)

205

Spain

3, 6 and 12 months following pre-treatment Post-treatment

Treatment response (a 30% or greater reduction in PG-YBOCS total score at end point compared with baseline) Treatment response (PG-CGI-I rating of 1 [very much improved] or 2 [much improved]) Gambling frequency (days gambling in the previous month)

Ladouceur, Lachance, and Fournier (2009) Ledgerwood and Petry (2010)

89

Canada

171

USA

Group CBT

Depression (SCL-90-R) Anxiety (SCL-90-R) Obsessive–compulsive (SCL-90-R) Phobic anxiety (SCL-90-R) Schizotypal personality disorder (SCID-II) Paranoid-borderline personality disorder (SCID-II) Individual CBT Depression (BDI) Anxiety (BAI) Individual CBT and GA referral or Subtypes based on CBT workbook and GA referral or depression (BSI), anxiety GA referral only (BSI) and impulsivity (EIS-7)

Post-treatment and 12 months follow-up Post-treatment and 6 or 12 months follow-up

Relapse (any episode of gambling associated with the main gambling problem during treatment or follow-up)

Treatment success (not meeting DSM-IV criteria) Gambling symptom severity (changes in ASI-G scores) Treatment response (scoring less than 5 on the SOGS) Asymptomatic (scoring 0 on the SOGS)

N.A. Dowling et al. / Addictive Behaviors 58 (2016) 21–30

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Table 1 (continued) Study

Sample size

Country

Manning et al. (2014)a

284

Milton, Crino, Hunt, and Prosser (2002)

Treatment type

Psychiatric comorbidity

Timing of treatment outcome assessment

Gambling outcome(s)

Singapore Individual CBT

Nicotine use

40

Australia

Individual CBT or individual CBT plus compliance improving intervention

Depression (BDI) Anxiety (STAI) Alcohol use problems (AUDIT) Substance use problems (DAST)

3 months following pre-treatment 9 month follow-up

Pallanti, Quercioli, Sood, and Hollander (2002) Smith, Battersby, Harvey, Pols, Baigent & Oakes (2011)

31

USA

Lithium or valproate

Past substance use problem (SCID)

Post-treatment

Reliable Change Index (past-month gambled days; G-SAS) Clinically significant change (scoring 5 or more on the SCIP; scoring 5 or more on the SOGS; at least 50% change in percentage of net monthly income lost gambling in previous month) Gambling symptom severity (YBOCS-PG total score)

127

Australia

Individual exposure therapy

Alcohol use problems (AUDIT) Anxiety (STAI and DASS-21) Depression (DASS-21)

1, 3, 6 and 12 months Problem gambling status (score of follow-up (analysis of 21+ on VGS harm to self subscale) predictors over time, as such included in 12

Toneatto, Skinner, and Dragonetti (2002)

79–126

Canada

Group CBT, individual brief MI, group 12-step therapy, or individual solution focused therapy (collapsed treatment groups after establishing no group differences)

Substance use (single items measuring lifetime cannabis, prescription opiate, hallucinogen, cocaine, stimulant, heroin, and inhalant use)

Zimmerman, Breen, and Posternak (2002)

15

USA

Citalopram

Major depressive disorder (SCID)

month follow-up) Post-treatment and 12 month follow-up

3 month post baseline

Improved (percentage abstinent; meeting criteria on SOGS; meeting criteria on DSM-IV) Gambling frequency (days abstinent in month prior to assessment) Gambling symptom severity (SOGS) Gambling symptom severity (DSM-IV) Gambling symptom severity (YBOCS-PG) Gambling symptom severity (OCDS-PG) Gambling frequency Gambling expenditure

ASI-G = Addiction Severity Index Gambling Composite; AUDIT = Alcohol Use Disorders Identification Test; BAI = Beck Anxiety Inventory; BDI = Beck Depression Inventory; BSI = Brief Symptom inventory; DASS — 21 Depression Anxiety Stress 21; DAST = Drug Abuse Screening Test; DSM-IV = Diagnostic and Statistical Manual; EIS-7 = Eysenck Impulsivity Scale-7; GABS = Gambling Attitudes and Beliefs Scale; G-SAS = Gambling symptom assessment scale; HADS = Hospital Anxiety and Depression Scale; MMPI-II = Minnesota Multiphasic Personality Inventory-II Addiction Acknowledgement Scale); NODS = NORC Diagnostic Screen for Gambling Disorders; OCDS-PG = Obsessive Compulsive Drinking Scale modified for Pathological Gambling; PG-YBOCS = Yale Brown Obsessive Compulsive Scale adapted for Problem Gambling; PG-CGI = Pathological Gambling Clinical Global Impression scale; PGSI = Problem Gambling Severity Index; SCID = Structured Clinical Interview for DSM Disorders; SCIP = Structured Clinical Interview for Pathological Gambling; SCL-90R = Symptom Checklist 90 Revised; SOGS = South Oaks Gambling Screen; VGS = Victorian Gambling Screen. a Provided different data from same study.

gambling behavior, anger and substance use at 12 week follow-up in 42 problem gamblers. Toneatto et al. (2009) evaluated the effectiveness of naltrexone (in conjunction with CBT) for 52 concurrent alcohol abuse/ dependence and problem gambling in an 11-week randomized, double-blind, placebo-controlled trial. Although naltrexone was not more effective than placebo for any alcohol or gambling variables at post-treatment or one year follow-up, significant improvements in alcohol and gambling were found for both groups, which may be attributed to the conjunctive CBT. More recently, Grant et al. (2014) examined whether the addition of N-acetylcysteine improved outcomes for 28 problem gamblers with comorbid nicotine dependence in a 12 week treatment program of Ask–Advise–Refer therapy (tobacco support) (6 weeks) and imaginal desensitization plus MI (6 weeks). The addition of N-acetylcysteine was associated with a significant reduction in problem gambling severity, but not nicotine dependence severity, at 3 month follow-up compared to augmentation with a placebo pill, suggesting that it may facilitate maintenance of behavioral therapy techniques for problem gambling after treatment completion.

3.2. Mood disorders Mood disorders are highly comorbid with problem gambling, with 23.1% of treatment-seeking problem gamblers reporting any mood disorder, specifically major depressive disorder (29.9%), bipolar disorder (8.8%), and dysthymic disorder (6.7%) (Dowling et al., 2015b). There is little available research exploring the degree to which mood disorders influence the clinical presentation of problem gamblers. According to retrospective age of onset analyses, mood

disorders typically predate the onset of problem gambling and predict the subsequent onset and persistence of problem gambling (Kessler et al., 2008). Other longitudinal research suggests that there is a weak predictive relationship between depressive symptoms and subsequent problem gambling (Dowling, Merkouris, et al., 2015) and that problem gambling is associated with the subsequent occurrence of any mood disorder and bipolar disorder, but not major depressive disorder or dysthymic disorder (Chou & Afifi, 2011). The first search identified 12 studies that explored whether depression influences treatment efficacy, but none that explored the influence of mania or bipolar disorder. Some of these studies have reported that depression negatively influences CBT (Breen et al., 2001; Ladouceur et al., 2009) and behavioral (Smith, Battersby, et al., 2011) treatment outcomes. There is, however, more evidence that depression does not impact outcomes following CBT (Dowling, 2009; Guo et al., 2014; Jimenez-Murcia et al., 2007; Ladouceur et al., 2009; Milton et al., 2002), imaginal desensitisation plus MI (Grant et al., 2011), citalopram (Zimmerman et al., 2002), N-acetylcysteine (Grant et al., 2007), naltrexone or nalmefene (Grant et al., 2008), or memantine (Grant et al., 2010), suggesting that these may be effective treatments for problem gamblers with comorbid depression. In the second search, a 10-week double-blind placebo-controlled trial of sustained-release lithium in 29 problem gamblers with comorbid bipolar spectrum disorders was identified (Hollander, Pallanti, et al., 2005). Lithium simultaneously improved gambling and bipolar disorder symptoms compared to placebo, underscoring the reciprocal influence between impulsivity and bipolarity in problem gamblers with bipolar spectrum comorbidity.

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Table 2 Characteristics of included studies from second systematic search. Study

Sample size

Country Treatment type

Control group

Psychiatric comorbidity

Post-treatment assessments

Gambling outcomes

Echeburua, Gomez, and Freixa (2011)

44

Spain

CBT plus standard drug treatment for schizophrenia

Standard drug treatment for schizophrenia

Chronic schizophrenia (measure not reported)

Post-treatment, and 1-, 3-, 6-, and 12-month follow-up

Grant et al. (2014)

28

USA

Placebo plus Ask–Advise–Refer therapy plus imaginal desensitisation/MI

Nicotine dependence

Post-treatment and 3 month follow-up

Grant and Potenza (2006)

13 (open-label); USA 4 (RCT)

N-acetylcysteine plus Ask–Advise–Refer therapy plus imaginal desensitisation/MI Escitalopram

Therapeutic success (defined as abstinence or the occurrence of only 1 or 2 episodes of gambling during the follow-up period); number of gambling episodes in the previous month; amount of money spent weekly on gambling PG-YBOCS

Placebo

Anxiety disorders (SCID)

Post-treatment (11 weeks open-label; 8

Toneatto, Brands, and Selby (2009)

52

Canada

Naltrexone plus CBT

Placebo plus CBT

Korman et al. (2008)

42

Canada

Modified DBT

Hollander, Pallanti, Allen, Sood, & Rossi (2005)

29

USA

Sustained-release lithium

Specialised treatment-as-usual (TAU) for gambling and substance use (eclectic including CBT relapse prevention) Placebo

Alcohol or substance use disorder Anger and alcohol/substance use disorder

Bipolar spectrum disorders

weeks RCT) Post-treatment and 12 month follow-up Post-treatment and 3 month follow-up

Post-treatment

Treatment response (30% or greater reduction in PG-YBOCS total score); G-SAS; CGI-Severity Days gambling and expenditure/gambling day PGSI; percentage of monthly income spent gambling

Treatment response (a 35% or greater reduction in PG-YBOCS total score at end point compared with baseline and a score of 1 or 2 on the CGI Improvement Scale [“very much improved” or “much improved”])

CGI = Clinical Global Impression scale; G-SAS = Gambling symptom assessment scale; PG-YBOCS = Yale Brown Obsessive Compulsive Scale adapted for Problem Gambling; PGSI = Problem Gambling Severity Index; SCID = Structured Clinical Interview for DSM Disorders.

3.3. Anxiety disorders There are also high rates of anxiety disorders reported by individuals seeking treatment for their gambling problems, with 17.6% of treatment-seeking problem gamblers reporting any anxiety disorder, specifically social phobia (14.9%), generalised anxiety disorder (14.4%), panic disorder (13.7%), post-traumatic stress disorder (PTSD) (12.3%), and obsessive–compulsive disorder (8.2%) (Dowling et al., 2015b). Ledgerwood and Petry (2006) found that problem gamblers with high PTSD symptoms reported greater problem gambling severity, psychiatric symptoms, impulsivity, and dissociation than those with low PTSD symptoms. Using retrospective age of onset data, Kessler et al. (2008) found that anxiety disorders (except PTSD) typically predate the onset of problem gambling and predict the subsequent onset and persistence of problem gambling. This data also suggests that problem gambling predicts the subsequent occurrence of some anxiety disorders, but not panic disorder or generalised anxiety disorder. In contrast, data from more recent longitudinal studies suggest that anxiety symptoms do not seem to be predictive of subsequent problem gambling (Dowling, Merkouris, et al., 2015) and that problem gambling only predicts some anxiety disorders (generalised anxiety disorder and PTSD) (Chou & Afifi, 2011). Twelve articles that investigated the degree to which anxiety influences the efficacy of problem gambling treatment were identified in the first search. There is some evidence that anxiety negatively influences outpatient CBT treatment outcomes (Ladouceur et al., 2009). There is, however, more evidence that anxiety does not impact outcomes following CBT (Dowling, 2009; Guo et al., 2014; Jimenez-Murcia et al., 2007; Ladouceur et al., 2009; Milton et al., 2002), behavioral treatments (Blaszczynski et al., 1991a, 1991b; Smith, Battersby, et al., 2011),

imaginal desensitisation plus MI (Grant et al., 2011), N-acetylcysteine (Grant et al., 2007), naltrexone or nalmefene (Grant et al., 2008), or memantine (Grant et al., 2010). These treatments may therefore be effective for problem gamblers with comorbid anxiety disorders. The second search identified an 11-week open-label study of escitalopram followed by an 8-week double-blind discontinuation study for problem gamblers with comorbid anxiety disorders (Grant & Potenza, 2006). In the open-label phase, 8 out of 13 (61.5%) participants were responders to escitalopram. Anxiety and gambling symptom improvement occurred concurrently, suggesting that these symptoms may be simultaneously targeted for treatment. In the discontinuation phase, the 3 escitalopram responders randomised to escitalopram reported slightly worse gambling symptoms that failed to reach clinical or statistical significance. 3.4. Attention deficit hyperactivity disorder (ADHD) The prevalence of comorbid ADHD in treatment-seeking gambling samples is 9.3% (Dowling et al., 2015b). Problem gamblers with history of ADHD have higher problem gambling severity, gambling-related cognitions, psychiatric comorbidity, suicide attempts, impulsivity, and personality disorder pathology than those without a history of ADHD (Grall-Bronnec et al., 2011; Specker, Carlson, Christenson, & Marcotte, 1995; Waluk, Youssef, & Dowling, 2015). Both longitudinal (Breyer et al., 2009) and retrospective age of onset data (Kessler et al., 2008) suggest that ADHD predates and predicts the development of problem gambling. In the first search, one study indicating that ADHD symptoms do not influence the effectiveness of bupropion was identified (Black et al., 2007), which suggests that bupropion may be worthy of further investigation for the treatment of problem gamblers with ADHD

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symptoms. The second search failed to identify any trials exploring the efficacy of interventions developed for problem gamblers with comorbid ADHD features. 3.5. Impulse control disorders Problem gamblers seeking treatment for gambling problems report a range of comorbid impulse control disorders, such as intermittent explosive disorder (4.6%) and kleptomania (2.7%) (Dowling et al., 2015b). Problem gamblers with a comorbid impulse control disorder report significantly greater intensity of urges, gambling-related thoughts, interference, and gambling-related distress than those without such comorbidity (Grant & Kim, 2003). Retrospective age of onset analyses indicate that comorbid impulse control disorders begin at an earlier age than problem gambling and predict the subsequent onset of problem gambling (Kessler et al., 2008). Meta-analytic results confirm that impulsivity is significantly positively associated with the development of problem gambling (Dowling, Merkouris, et al., 2015). The first search in this mini-review identified one study that found that comorbid impulse control disorders do not affect the effectiveness of imaginal desensitisation plus MI (Grant et al., 2011). This finding implies that this intervention may be appropriate for problem gamblers with comorbid impulse control disorders. The second search, however, failed to identify any trials investigating the efficacy of interventions for problem gamblers with comorbid impulse control disorders. 3.6. Schizophrenia Although the rate of psychotic disorders in treatment-seeking problem gamblers is 4.7% (Dowling et al., 2015b), there is little available research exploring the degree to which psychotic symptoms influence their clinical presentation or the temporal nature of the relationship. Although the first search failed to identify any studies investigating the impact of psychotic symptoms on gambling treatment outcomes, the second search identified a trial that randomly allocated 44 patients diagnosed with chronic schizophrenia and problem gambling to an experimental group (CBT for problem gambling and standard drug therapy for schizophrenia) and a waiting list control group (standard drug therapy for schizophrenia) (Echeburua et al., 2011). At the 3 month followup evaluation, therapeutic success for gambling behavior was significantly higher for the experimental condition (73.9%) than the control condition (19.0%). This study failed to measure psychotic symptoms as an outcome of treatment. 3.7. Eating disorders Few studies have explored the prevalence of eating disorders in treatment-seeking problem gamblers (Dowling et al., 2015b), investigated how these disorders impact on the clinical presentation of gamblers, or explored the temporal nature of the relationship between problem gambling and these disorders. One study was identified in the first search indicating that eating disorders (binge eating disorder and bulimia nervosa) failed to predict the outcomes from imaginal desensitisation plus MI (Grant et al., 2011). Behavioral and MI interventions may therefore be worthy of further investigation in the treatment of problem gamblers with comorbid eating disorders. No study evaluating an intervention for problem gamblers with eating disorders was identified in the second search. 3.8. Personality disorders Nearly half (47.9%) of treatment-seeking problem gamblers report comorbid personality disorders, specifically narcissistic (16.6%), antisocial (14.0%), avoidant (13.4%), obsessive–compulsive (13.4%), and borderline (13.1%) personality disorders (Dowling et al., 2015a). Treatment-seeking gamblers with comorbid personality disorders, particularly antisocial

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personality disorder, report higher problem gambling duration, problem gambling severity, gambling-related consequences, impulsivity, psychiatric symptoms, psychological distress, substance use difficulties, and medical problems, and lower distress tolerance, than other problem gamblers (Blaszczynski & McConaghy, 1994; Blaszczynski & Steel, 1998; Blaszczynski, Steel, & McConaghy, 1997; Brown, Oldenhof, Allen, & Dowling, 2016; Grall-Bronnec et al., 2011; Kruedelbach et al., 2006; Pietrzak & Petry, 2005). Because the diagnostic criteria locate personality disorder traits in late adolescence or early adulthood, it is often presumed that they precede the onset of gambling problems (Bagby, Vachon, Bulmash, & Quilty, 2008). In this review, the first search identified only one study. This study found that schizotypal and paranoid-borderline personality disorders were unrelated to gambling outcomes following CBT (Jimenez-Murcia et al., 2007), implying that CBT may be an effective intervention for problem gamblers with these comorbid disorders. The second search, however, failed to identify any trials that have evaluated interventions for problem gamblers with comorbid personality disorders. 3.9. Problem gambling subtypes Problem gambling typologies, which attempt to account for the heterogeneity observed in problem gambling, may provide a conceptual framework within which to develop the most effective treatments for problem gambling. Blaszczynski and Nower's (2002) pathways model proposes three major entry pathways into problem gambling: (1) behaviourally conditioned problem gamblers who have little psychopathology and develop problem gambling as a consequence of the highly addictive reinforcement schedule of gambling; (2) emotionally vulnerable problem gamblers who have a biological and emotional vulnerability to gambling with high levels of depression and/or anxiety, and who gamble as a form of emotional escape; and (3) antisocial problem gamblers, who are characterised by a history of impulsivity and antisocial behavior, and have neurological and neurochemical dysfunction. There is growing empirical evidence supporting this typology (Ledgerwood & Petry, 2010; Milosevic & Ledgerwood, 2010; Nower, Martins, Lin, & Blanco, 2013; Suomi et al., 2014). Treatment options have been recommended for each pathway (Blaszczynski & Nower, 2002; Milosevic & Ledgerwood, 2010). Behaviourally conditioned problem gamblers may respond to brief interventions using psychoeducation and basic cognitive therapy designed to correct irrational beliefs or home-based imaginal desensitization. Problem solving and stress-based interventions involving more extensive CBT, treatments that address underlying depression and anxiety symptoms (such as SSRIs), or interventions that enhance adaptive coping with negative affective states (such as supportive-expressive psychotherapy) may be warranted for the emotionally vulnerable subgroup. In contrast, the antisocial subgroup may require adjunct pharmacology (such as mood stabilizers), intensive CBT, and impulse-control strategies. Another theoretically-derived typology developed by Dannon et al. (2006); Iancu, Lowengrub, Dembinsky, Kotler, & Dannon, 2008) posits that there are three different subtypes of problem gambling; (1) the “impulsive” subtype (predominantly young adult men with high levels of risk-taking, high gambling expenditures and gambling severity, an inability to plan ahead, and comorbid ADHD, alcohol and substance dependence, and impulse control disorders), (2) the “obsessive–compulsive” subtype (predominantly middle-aged women who develop gambling problems in response to psychological trauma, have high rates of mood and anxiety disorders, and prefer non-strategic forms of gambling); and (3) the “addictive” subtype (predominantly men who have high rates of alcohol use disorders, moderate gambling severity, and small but frequent gambling losses). Treatment recommendations for each of these subtypes (Dannon et al., 2006; Iancu et al., 2008) include pharmacological agents targeting impulsive behavior (i.e., bupropion or mood stabilizers), with

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adjunctive SSRI or SNRI and opioid antagonists for the “impulsive” subtype. The “obsessive–compulsive” subtype may respond best to psychoactive medications that target depression, anxiety and compulsive behavior (such as SSRIs and SNRIs) followed by mood stabilizer monotherapy, bupropion or naltrexone. Psychological interventions involving stress reduction and coping mechanisms may also be helpful for this subtype. Finally, the “addictive” subtype may respond best to bupropion, followed by opioid antagonists, then SSRI/mood stabilizer mono- or combination therapy. Despite these recommendations, the first search identified only one study that has examined treatment outcomes for problem gambling subtypes (Ledgerwood & Petry, 2010). Based on depression, anxiety, and impulsivity measures, problem gamblers were classified into subgroups according to the pathways model and were treated with CBT and/or GA. Although all three subtypes demonstrated similar patterns in treatment response, the behaviourally conditioned subgroup began treatment with less gambling severity and were more likely to improve post-treatment and at the 12 month follow-up evaluation. The authors argued that the subtypes did not predict treatment outcomes above and beyond associations with problem gambling severity but that the emotionally vulnerable and antisocial impulsivist subtypes may require more intensive treatment as a result of their higher levels of problem severity prior to treatment. The second search failed to identify any trials that have evaluated interventions specifically designed for problem gambling subtypes. 4. Discussion Despite our understanding of the significant heterogeneity in problem gambling, this mini-review indicates that we have very little evidence on which to base treatment recommendations for different subpopulations of problem gamblers based on their psychiatric comorbidity. This study identified only 21 studies that have conducted posthoc analyses to explore the influence of psychiatric disorders or problem gambling subtypes on well-specified problem gambling treatments. Interestingly, most treatments are not contraindicated by most psychiatric disorders, although the response of many subgroups across and within studies to CBT was mixed, likely due to the larger amount of research investigating the efficacy of CBT relative to other interventions. In contrast, only 6 studies investigating the efficacy of interventions targeted towards specific problem gambling subgroups were identified. These studies provide preliminary evidence for the efficacy of modified dialectical behavior therapy for comorbid substance use, the addition of naltrexone to CBT for comorbid alcohol use problems, and the addition of N-acetylcysteine to tobacco support programs and imaginal desensitization/motivational interviewing for comorbid nicotine dependence. They also suggest that lithium for comorbid bipolar disorder, escitalopram for comorbid anxiety, and the addition of CBT to standard drug treatment for comorbid schizophrenia may be effective. These treatments were effective, not only in improving the gambling behavior, but also in decreasing the symptomatology of the comorbid psychiatric condition (Hollander, Pallanti, et al., 2005; Grant & Potenza, 2006; Korman et al., 2008; Toneatto et al., 2009). The degree to which problem gamblers with comorbid conditions transfer their interest to other addictive behaviors following administration of these interventions, however, remains unclear. Although not highlighted in this review, it may also be important to note that there are several non-randomized trials, case studies or small sample designs exploring the efficacy of specific interventions for problem gamblers with comorbid alcohol or substance use disorders (Crockford & el-Guebaly, 1998; Lesieur & Blume, 1991), bipolar spectrum disorders (Dell'Osso & Hollander, 2005; Moskowitz, 1980; Nicolato, Romano-Silva, Correa, Salgado, & Teixeira, 2007), posttraumatic stress disorder (Najavits et al., 2013), and schizophrenia (Potenza & Chambers, 2001; Shonin, Van Gordon, & Griffiths, 2014; Smith, Kitchenham, et al., 2011).

Despite these advances, important and fundamental research questions relating to the treatment implications of psychiatric comorbidity and the conditions under which treatments work remain to be examined. The mini-review findings identified very little empirical literature for some comorbid disorders, such as personality disorders, ADHD, adjustment disorders, psychotic disorders, impulse control disorders, eating disorders, and somatoform disorders, despite some of these disorders being relatively highly comorbid with problem gambling (Dowling et al., 2015a; Dowling et al., 2015b). Given that comorbidity is generally the rule rather than the exception, all research exploring the efficacy of interventions for problem gambling should measure comorbidity and explore its impact on outcomes. Research should also employ measures of alcohol and substance use to ensure that symptom substitution does not occur. Moreover, the efficacy of interventions specifically designed for particular subpopulations of problem gamblers with comorbid disorders using RCT methodologies is required. Future research would also benefit from additional empirical evaluations of the treatment outcomes for problem gambling subtypes. Moreover, to date, there are few studies attempting to clarify whether problem gambling and comorbid conditions should be treated concomitantly or sequentially (Winters & Kushner, 2003). If the disorders are to be treated sequentially, it is unclear if the sequence of treatment should be determined according to the severity of the disorders or the functional relationship between the gambling behavior and comorbid symptomatology (Hollander, Sood, Pallanti, Baldini-Rossi, & Baker, 2005; Toneatto & Millar, 2004; Winters & Kushner, 2003). Many psychiatric disorders predate and predict the onset of problem gambling, but problem gambling also predicts the subsequent occurrence of several disorders (Chou & Afifi, 2011; Dowling, Merkouris, et al., 2015; Kessler et al., 2008). Although it may therefore be important to consider the functional relationship between the gambling behavior and comorbid symptomatology, the comorbid disorder may impact on the effectiveness of treatment even when multiple disorders within the one individual are etiologically independent (Hollander, Sood, et al., 2005; Winters & Kushner, 2003). As such, Winters and Kushner (2003) recommend: (1) screening for comorbid disorders upon admission to problem gambling treatment, (2) monitoring comorbid disorder symptomatology as treatment for problem gambling begins, (3) reassessment of the comorbid disorder after an asymptomatic period has been established for problem gambling, and (4) administration of specific treatments for the comorbid condition should it persist in the absence of active gambling behavior. Further research exploring the effect of such sequenced interventions on problem gambling outcomes is required. Given that problem gambling is a relatively low base-rate phenomenon (Christensen, Dowling, Jackson, & Thomas, 2015; Dowling, Jackson, et al., 2015; Williams, Volberg, & Stevens, 2012) and that the rate of seeking help for gambling is extremely low (8–17%) (Productivity Commission, 2010), it may not be pragmatic to restrict samples of treatment-seeking problem gamblers according to psychiatric comorbidities in treatment outcome studies. Moreover, there is evidence that a substantial proportion of treatment-seeking problem gamblers have multiple comorbid conditions (Ibanez et al., 2001; Kerber, Black, & Buckwalter, 2008; Kessler et al., 2008; Kruedelbach et al., 2006; Westphal & Johnson, 2007. Taken together, these findings suggest that research designs other than RCTs may be useful in the exploration of the influence of psychiatric comorbidities on problem gambling treatment. For example, there are currently no available studies attempting to identify the degree to which psychiatric comorbidities moderate the efficacy of problem gambling interventions. In clinical research, moderators are variables that specify the conditions under which a treatment is effective and the individuals for whom therapies work relative to other individuals and therapies. According to Kraemer (2008, p. 1680), “any baseline, pre-randomisation variable is potentially a moderator of treatment outcome and may be used to identify which subpopulations are or are not benefited more by one treatment than by

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another treatment”. Employing such techniques can potentially allow for statistical control of other comorbid psychiatric conditions or test the influence of multiple psychiatric comorbidities on problem gambling treatment. Research aimed at identifying comorbid psychiatric disorders as moderators of change may increase the efficacy of treatment by clarifying theoretical issues, identifying different causal chains leading from treatment to outcome for different subgroups of problem gamblers, and eliminating unnecessary elements of treatment (Kraemer, 2008; Weisz & Hawley, 1998). They may also assist in the development of more refined research designs, such as the stratification of samples on that moderator, or a focus on a particular comorbidity, in future RCTs (Kraemer, 2008). Another way to maximise the relatively small samples of eligible problem gamblers seeking treatment is to examine the joint impact of multiple treatment “matches” and “mismatches”. To date, no published studies have explored the efficacy of interventions matched to client comorbidity, or clusters of comorbid conditions, compared to nonmatched interventions. Previous research in other fields has revealed that “matched” groups of participants who were matched on one or more factors (with no mismatches) have better outcomes than a “mismatched” group of participants who were mismatched on one or more factors (with no matches) (Longabaugh et al., 2005). It is argued that considering multiple factors may be more useful for treatment recommendations by serving to explain a larger proportion of variance in treatment outcomes. Role of funding sources There was no direct funding for this manuscript. The Problem Gambling Research and Treatment Centre at the University of Melbourne, with which several co-authors were affiliated when the data was collected, was previously supported by the Victorian Responsible Gambling Foundation. The Victorian Responsible Gambling Foundation had no involvement in the current publication. Contributors Author A developed the review protocol, extracted the data, and wrote the first draft of the manuscript. Author B conducted the systematic searches, created the PRISMA diagrams, and provided secondary data extraction. Author C contributed to the conceptual rationale for the article and assisted in drafting the initial manuscript and revisions. All authors have contributed to and have approved the final manuscript. Conflict of interest All authors declare that they have no conflicts of interest.

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