Psychological interventions for post-traumatic stress disorder and comorbid substance use disorder: A systematic review and meta-analysis.

Clinical Psychology Review 38 (2015) 25–38

Contents lists available at ScienceDirect

Clinical Psychology Review

Psychological interventions for post-traumatic stress disorder and comorbid substance use disorder: A systematic review and meta-analysis Neil P. Roberts a,b,⁎, Pamela A. Roberts b,c, Neil Jones c, Jonathan I. Bisson a a b c

Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK Psychology and Counselling Directorate, Cardiff and Vale University Health Board, Cardiff, UK Community Addiction Service, Cardiff and Vale University Health Board, Cardiff, UK

H I G H L I G H T S • • • • •

Comorbid PTSD and SUD are difficult to treat. Drop-out from treatment is high. There is evidence of benefit from approaches that include trauma-focused intervention. There is little evidence for non-trauma-focused approaches at present. The quality of current evidence is low.

a r t i c l e

i n f o

Article history: Received 14 October 2014 Received in revised form 20 January 2015 Accepted 24 February 2015 Available online 3 March 2015 Keywords: Posttraumatic stress disorder Substance use disorder Comorbidity Psychological intervention Meta-analysis

a b s t r a c t Co-morbid post-traumatic stress disorder (PTSD) and substance use disorder (SUD) are common, difficult to treat, and associated with poor prognosis. This review aimed to determine the efficacy of individual and group psychological interventions aimed at treating comorbid PTSD and SUD, based on evidence from randomised controlled trials. Our pre-specified primary outcomes were PTSD severity, drug/alcohol use, and treatment completion. We undertook a comprehensive search strategy. Included studies were rated for methodological quality. Available evidence was judged through GRADE. Fourteen studies were included. We found that individual trauma-focused cognitive–behavioural intervention, delivered alongside SUD intervention, was more effective than treatment as usual (TAU)/minimal intervention for PTSD severity post-treatment, and at subsequent follow-up. There was no evidence of an effect for level of drug/alcohol use post-treatment but there was an effect at 5–7 months. Fewer participants completed trauma-focused intervention than TAU. We found little evidence to support the use of individual or group-based nontrauma-focused interventions. All findings were judged as being of low/very low quality. We concluded that there is evidence that individual trauma-focused psychological intervention delivered alongside SUD intervention can reduce PTSD severity, and drug/alcohol use. There is very little evidence to support use of non-trauma-focused individual or group-based interventions. © 2015 Elsevier Ltd. All rights reserved.

Contents 1. 2. 3.

Introduction . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . 2.1. Outcomes . . . . . . . . . . . . . . Data extraction . . . . . . . . . . . . . . . 3.1. Assessment of methodological quality . . 3.2. Main and subgroup analyses . . . . . . 3.3. Statistical analyses and quality of evidence

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⁎ Corresponding author at: Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK. E-mail address: [email protected] (N.P. Roberts).

http://dx.doi.org/10.1016/j.cpr.2015.02.007 0272-7358/© 2015 Elsevier Ltd. All rights reserved.

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N.P. Roberts et al. / Clinical Psychology Review 38 (2015) 25–38

4.

Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.1. Individual trauma-focused approaches . . . . . . . . . . . 4.1.2. Individual non-trauma-focused approaches for PTSD and SUD . 4.1.3. Group-based non-trauma-focused approaches for PTSD and SUD 4.1.4. Individual non-trauma-focused approaches for PTSD only . . . 4.1.5. Quality of methodology . . . . . . . . . . . . . . . . . . 4.2. Assessed outcomes and evidence synthesis . . . . . . . . . . . . . 4.2.1. Individual trauma-focused intervention . . . . . . . . . . . 4.2.2. Individual non-trauma-focused intervention . . . . . . . . . 4.2.3. Group-based non-trauma-focused intervention . . . . . . . 4.2.4. Individual non-trauma-focused intervention for PTSD only . . 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Role of funding sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . Author contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appendix A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appendix B. Study characteristics related to the risk of bias . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction Post-traumatic stress disorder (PTSD) and Substance Use Disorder (SUD) are common and well recognised psychiatric disorders with established psychological and pharmacological treatment approaches. For PTSD trauma-focused cognitive behavioural therapies and Eye Movement Desensitisation (EMDR) are currently the most efficacious psychological treatments (Bisson, Roberts, Andrew, Cooper, & Lewis, 2013; Bradley, Greene, Russ, Dutra, & Westen, 2005). For SUD a number of interventions based on the principles of CBT and behaviour therapy have been found to be effective. These include coping skills training, relapse prevention, contingency management and behavioural couples' therapy (Knapp, Soares, Farrell, & Silva de Lima, 2007; Mayet, Farrell, Ferri, Amato, & Davoli, 2004; Powers, Vedel, & Emmelkamp, 2008). Comorbidity between PTSD and SUD is common: amongst individuals with SUD, the prevalence of lifetime PTSD ranges from 26% to 52%, with prevalence of current PTSD ranging from 15% to 42% (Dragan & Lis-Turlejska, 2007; Driessen et al., 2008; Mills, Teeson, Ross, & Peters, 2006; Reynolds, Hinchliffe, Asamoah, & Kouimtsidis, 2011; Reynolds et al., 2005; Schäfer et al., 2010). In PTSD diagnosed samples, the prevalence of co-morbid SUD (excluding alcohol use disorder) ranges from 19% to 35% (Breslau & Davis, 1992; Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995; Mills et al., 2006; Pietrzak, Goldstein, Southwick, & Grant, 2011). Alcohol use disorder (AUD) has consistently been found to be the most commonly cooccurring SUD co-morbidity, with prevalence rates ranging from 36% to 52% (Breslau & Davis, 1992; Kessler et al., 1995; Mills et al., 2006; Pietrzak et al., 2011). Prevalence rates for both alcohol and drug abuse appear to be higher for men with PTSD than women (Kessler et al., 1995). Estimates of comorbidity have been even higher in some populations, such as combat veterans (Jacobsen, Southwick, & Kosten, 2001; Keane & Wolfe, 1990; Kulka et al., 1990; McDevitt-Murphy et al., 2010). Patients with both disorders have been found to have a more severe clinical profile than those with either disorder alone, lower general functioning, poorer well-being and worse outcomes across a variety of measures (Schäfer & Najavits, 2007). Co-morbidity with other psychiatric disorders, such as affective disorders, anxiety disorders and personality disorders is also increased. This results in additional individual, familial and societal burdens (Mills et al., 2006; Schäfer & Najavits, 2007). For these reasons, randomised controlled

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trials evaluating PTSD treatment interventions routinely exclude individuals with substance misuse-related problems (Ouimette et al., 2003). Individuals with PTSD and SUD co-morbidity are perceived as being more difficult to treat than individuals with either condition alone, for various reasons (Schäfer & Najavits, 2007). The comorbidity is associated with poorer recruitment and retention in treatment programs, poorer treatment outcomes, poorer treatment adherence, and shorter periods of abstinence posttreatment (Brown, Read, & Kahler, 2003; Foa & Williams, 2010; Ouimette et al., 2003; Ouimette, Moos, & Finney, 2003; Reynolds et al., 2005; Schäfer & Najavits, 2007). Despite high prevalence levels, adults in treatment for SUD are frequently not assessed for PTSD or offered PTSD-based interventions (Ford, Hawke, Alessi, Ledgerwood, & Petry, 2007; Mills et al., 2006; Ouimette et al., 2003; Reynolds et al., 2005). Most diagnosis-specific guidelines for PTSD make little reference to whether specific treatment recommendations apply to SUD co-morbidity (Watkins, Hunter, Burnam, Pincus, & Nicholson, 2005) and there is no real consensus about best practice. Many clinicians still argue the SUD should be treated first (e.g., Busuttil, 2009; Zayfert & Becker, 2007), or that abstinence is necessary before diagnosis and a management plan can be made (e.g., Busuttil, 2009). The reality is that patients frequently get passed between services with little co-ordination of care (Najavits, 2006). A number of different explanations for the relationship between SUD and PTSD have been proposed (Meyer, 1986; Schäfer & Najavits, 2007). One explanation is that problematic substance use increases the risk of being exposed to trauma and psychological vulnerability to the effects of trauma (Meyer, 1986; Schäfer & Najavits, 2007). A second explanation is that individuals with PTSD may seek symptom relief through drug or alcohol use, potentially leading to the development of SUD (Khantzian, 1985; Kline et al., 2014; Schäfer & Najavits, 2007). This has become known as the “self-medication hypothesis” (Khantzian, 1985). A third explanation is that PTSD and SUD may stem from shared but independent aetiologies (Berenz & Coffey, 2012; Kline et al., 2014; Krueger & Markon, 2006). Proposed common liabilities include, shared genetic risk (e.g., Wolf et al., 2010), common personality traits, such as impulsivity (Schaumberg et al., 2015; Weiss, Tull, Viana, Anestis, & Gratz, 2012; Weiss, Tull, Anestis, & Gratz, 2013), and common environmental factors, such as trauma exposure (Kline et al., 2014).


A number of studies have investigated common maintaining factors, with a particular focus on coping capacity and coping styles. Two overlapping areas of coping that have received particular attention are difficulties with emotion regulation and avoidant coping. Emotion regulation difficulties are associated with increased symptom severity in individuals with PTSD (Cloitre, Miranda, StovalI-McCIough, & Han, 2005; Ehring & Quack, 2010) and in SUD (Kober, 2014). Poor capacity for emotion regulation has been found to be associated with PTSD SUD comorbidity (McDermott, Tull, Gratz, Daughters, & Lejuez, 2009), and has been found to mediate impulsivity in SUD patients with PTSD (Weiss et al., 2012; Weiss et al., 2013). Capacity for emotion regulation has also been suggested as an important factor influencing treatment attendance (Hien et al., 2012). Similarly, avoidant coping is also strongly associated with PTSD (Ehlers & Clark, 2000; Foa & Rothbaum, 1998; Pineles et al., 2011) and with SUD (Moos, 2007). Avoidant coping has also been associated with elevated symptomatology in individuals with PTSD and SUD comorbidity (Boden et al., 2014; Hruska, Fallon, Spoonster, Sledjeski, & Delahanty, 2011). Psychological interventions may, therefore, effect change in symptoms and functioning in such individuals through a number of different mechanisms. One potential mechanism by which psychological interventions might work is the development of enhanced coping skills, which may increase the ability to regulate negative emotions (Busuttil, 2009), leading to increased capacity to tolerate traumatic memories and craving urges. Another potential mechanism is the processing of trauma memories (Ehlers & Clark, 2000; Foa & Rothbaum, 1998) leading to a decreased need to engage in avoidant coping and ‘self-medication’. Psychological interventions such as those based on cognitive behavioural therapy (CBT) are also likely to promote changes in thinking and belief systems underlying trauma memories, and beliefs and ideas about substance use (Ehlers & Clark, 2000; Najavits, 2002). For example, such interventions may facilitate attitudinal change to substance misuse and aid increased understanding of cognitive and situational risk factors associated with patterns of drug taking or problematic drinking, particularly those factors associated with past trauma. Other change mechanisms might include the development and reinforcement of adaptive coping skills which support constructive coping with both conditions (Brown et al., 2003). It is likely that different interventions will operate though different means of change. There is a paucity of evidence for recommendations about treatment interventions for affective or anxiety disorders that are comorbid with substance use disorders (Watkins et al., 2005). In practice a wide range of pharmacological and psychological interventions are used to treat the comorbidity. In recognition of the clinical challenges involved in treating individuals with comorbid PTSD and SUD, a number of specialised psychological intervention approaches have been developed over the past 15 years or so. Two broad approaches have received most attention (van Dam, Vedel, Ehring, & Emmelkamp, 2012). The first approach, involves a trauma-focused therapy being delivered alongside established evidence-based interventions for SUD (Back, Dansky, Carroll, Foa, & Brady, 2001; van Dam et al., 2012). Intervention is usually delivered on an individual basis, and trauma-focused therapy usually involves processing of trauma memories through an exposure based approach (e.g., Foa & Rothbaum, 1998). The second approach normally involves treating both disorders at the same time through CBT or coping skill training, without an exposure-based trauma-focused component. These non-trauma-focused approaches have been delivered individually and through groups. Amongst non-trauma-focused models ‘Seeking Safety’ (Najavits, 2002) has probably received most attention with a number of randomised and non-randomised evaluative

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studies. Seeking Safety is a structured cognitive behavioural treatment with both safety/trauma and substance use components integrated into each session. Its primary goal is to reduce both PTSD and SUD by focusing on safe coping skills addressed through cognitive, behavioural, interpersonal, and case management domains. To our knowledge only two systematic reviews of psychological interventions have been undertaken in this area (Torchalla, Nosen, Rostam, & Allen, 2012; van Dam et al., 2012). Torchalla et al. (2012) undertook a review of psychological interventions for individuals with SUD and a history of psychological trauma and/ or presence of PTSD. This review, which included 17 studies, focused entirely on non-trauma-focused “integrated” interventions. Torchalla and colleagues found little difference in reduction of PTSD and SUD symptoms between integrated and non-integrated programs. Findings were mainly based on results from noncontrolled trials. The review by van Dam et al. (2012) had tighter inclusion criteria, including only studies where participants had a diagnosis of PTSD or partial PTSD and SUD. This review also included 17 studies: six RCTs, eight uncontrolled studies and three case studies. Most studies had rates of PTSD above 80% but in one study only 58% of participants met PTSD diagnosis (Triffleman, 2000). Findings were summarised through a narrative approach. Studies were evaluated on the basis of whether experimental interventions were non-trauma-focused or traumafocused approaches. Van Dam and colleagues found no convincing evidence to support the use of non-trauma focused therapies over routine interventions for SUD. They were only able to identify one small RCT (Coffey, Stasiewicz, Hughes, & Brimo, 2006), two small uncontrolled trials and three case studies evaluating trauma-focused interventions. They concluded that these studies highlighted some positive indication but felt that there was insufficient evidence to recommend trauma-focused interventions at the time. There are several methodological limitations to these two reviews. The search strategy of both reviews was limited to databases of published studies only, and unpublished studies were not searched for. The “file-draw effect” is a significant problem to for systematic reviews (Borenstein, Hedges, Higgins, & Rothstein, 2009). One means of mitigating this problem is through a comprehensive search strategy, which includes searching for unpublished trials. A further limitation of both reviews is that whilst they undertook evaluation of the methodologies of included studies, these evaluations were not systematic or structured and did not consider some of the key domains associated with risk of bias (Higgins & Green, 2011). Both reviews also acknowledged the limitations of basing their findings partly on non-controlled trials and case studies. Van Dam and colleagues noted that many of the studies that they included lacked methodological rigour and called for more well powered and rigorous randomised trials. Van Dam and colleagues also identified their qualitative analysis as a limitation and recommended that in the future findings should be synthesised through meta-analysis, once more methodologically sound studies were available. Since publication of these reviews a number of larger randomised controlled trials (RCTs) have been completed. We, therefore, took the view that the time was right to undertake a further systematic review, with meta-analysis where appropriate. We also felt that it was important to address some of the methodological limitations of these previous systematic reviews; in particular, to search for both published and unpublished studies, to undertake a structured evaluation of the methodologies of included trials and to base our findings on RCTs only. We set out to build particularly on the review undertaken by van Dam et al. (2012) by undertaking a review based on the guidelines set out by the Cochrane Collaboration (Higgins & Green, 2011). Our objective was to determine the efficacy of

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psychological interventions aimed at treating traumatic stress symptoms, substance misuse symptoms, or both, in individuals with co-morbid PTSD and SUD in comparison with control conditions (including usual care, waiting list conditions, and no treatment), and other psychological interventions. 2. Methods The RCT is widely considered to be the gold standard in treatment outcome research (Ehring et al., 2014), providing the most reliable, unbiased and rigorous means of acquiring evidence of the effectiveness of clinical interventions (Higgins & Green, 2011). In this review we considered any randomised or clusterrandomised controlled trial of one or more defined psychological intervention aimed at reducing traumatic stress symptoms, SUD symptoms, or both. We specified that any study had to include either a control condition (e.g., usual care or waiting list control) or an alternative psychological intervention condition. We did not use sample size, publication status or language to determine whether or not a study should be included. At least 80% of participants were required to be diagnosed as suffering from PTSD and SUD according to DSM or ICD criteria. For studies identified where a significant sub-set of participants met our inclusion criteria but the 80% threshold was not met, we approached the study authors to request outcome data for the subset with comorbid PTSD and SUD. There was no restriction on age, basis or severity of PTSD symptoms, type of traumatic event, nature of substance use, other co-morbidity or study setting. A systematic computerized literature search of the Cochrane Depression, Anxiety and Neurosis Group (CCDAN) clinical trials registers databases was performed for studies published up to 10 January 2014 using predefined search terms (see Appendix A). (These databases are collated and updated on a weekly basis from MEDLINE, EMBASE and PsycINFO.) We searched included studies for the Cochrane Review for psychological treatments for chronic PTSD (Bisson et al., 2013) and reviews of psychological intervention undertaken for the Cochrane Drug and Alcohol Group. We checked reference lists of studies identified in the search and of relevant systematic reviews. We searched the World Health Organization's, and the U.S. National Institutes of Health's trials portals to identify additional unpublished or ongoing studies. We also contacted experts in the field with the aim of identifying unpublished studies and studies that were in submission. 2.1. Outcomes We identified three primary outcomes: severity of traumatic stress symptoms using a standardised measure, reduction in drug, alcohol use or both as measured by a standardised measure, and treatment acceptability, as measured by number of participants still in treatment at the end of intervention. For PTSD and SUD symptoms primacy was given to standardised clinician administered instruments. We favoured biological markers over self-report for drug and alcohol use when these were the only outcomes available. Secondary outcomes were PTSD diagnostic status, SUD diagnostic status, adverse events, compliance as measured by proportion of treatment sessions attended, general functioning, and use of health related resources. 3. Data extraction Two authors independently read the titles or abstracts of all potential trials. If an abstract appeared to represent an RCT, each author reads the full report independently to determine if the trial met the inclusion criteria. When agreement could not be reached about inclusion another author was consulted. We used a data

extraction sheet to capture study characteristics and study data. Information extracted included demographic details of participants, details of the traumatic event, type of substance use, the randomisation process, the interventions used, drop-out rates, and outcome data. Three authors independently extracted data. When agreement could not be reached the issue was discussed with the fourth author. 3.1. Assessment of methodological quality We assessed methodological quality using the Cochrane Collaboration's tool for assessing risk of bias (Higgins & Green, 2011). We assessed the following domains: sequence generation, allocation concealment (selection bias), blinding of assessors (performance and detection bias), incomplete outcome data (attrition bias), selective outcome reporting and other sources of bias. We specified that we would consider sensitivity analysis to explore possible causes of methodological heterogeneity, if sufficient data allowed on the basis of allocation concealment, high level of post-randomisation losses or exclusions, and unblended or uncertain outcome assessment. 3.2. Main and subgroup analyses We followed van Dam et al. (2012) by dividing and analysing studies separately according to whether the experimental intervention was trauma-focused or non-trauma-focused. Intervention was defined as trauma-focused if it included a significant component involving processing of trauma memories through exposure based intervention (e.g., Foa & Rothbaum, 1998; Resick & Schnicke, 1993). Non-trauma-focused interventions have been delivered individually and through groups, we therefore decided to analyse separately on this basis. We also divided analyses on the basis of i) psychological intervention versus a treatment as usual/minimal intervention control or ii) psychological intervention versus an alternative active psychological intervention. 3.3. Statistical analyses and quality of evidence We analysed continuous outcomes using mean difference (MD) when all trials had measured the outcome on the same scale. When some trials measured outcomes on different scales we used the standardised mean difference (SMD). SMD was based on the Hedges' g (Hedges, 1981) and calculated by: SMD ¼

Difference in mean outcome between groups : Standard deviation of outcome among participants

We used risk ratio (RR) as the main categorical outcome measure. We also examined heterogeneity between studies by observing the Q statistic (P b 0.10) and the I 2 statistic. We used a random-effects model to summarise results as we expected substantial heterogeneity amongst the studies (Higgins & Green, 2011). We specified that in cases where significant heterogeneity was found to be present we would attempt to explain the variation. Data were analysed in Review Manager 5.3 (Review Manager (RevMan) Version 5.3.5, 2011). All P values are 2-tailed. We evaluated the quality of the results obtained using the “Grades of Recommendation, Assessment, Development, and Evaluation” (GRADE) approach (Guyatt, Oxman, Schünemann, Tugwell, & Knottnerus, 2011; Guyatt et al., 2013; Langendam et al., 2013). GRADE is a widely supported framework for evaluating the quality of evidence of findings from systematic reviews (Higgins & Green, 2011). We assessed the quality of evidence using five factors: Limitations in study design and implementation of available studies,


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28 records identified through additional sources (Unique records)

907 records identified through CCDAN

897 records after duplicates removed

745 records excluded

142 full text article assessed for eligibility + 7 protocols for ongoing studies + 3 conference abstracts followed up to in attempt to locate associated publication

128 records excluded + 7 ongoing studies + 3 awaiting classification

14 studies included in qualitative synthesis

13 studies included in metaanalysis

Fig. 1. Flow chart for the selection of eligible studies.

indirectness of evidence, unexplained heterogeneity or inconsistency of results, imprecision of effect estimates, and potential publication bias. For each outcome that included pooled data we classified the quality of evidence for each outcome according to the following categories: • High quality: further research is very unlikely to change our confidence in the estimate of effect. • Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. • Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. • Very low quality: we are very uncertain about the estimate. We downgraded the evidence from ‘high quality’ by one level for serious (or by two for very serious) study limitations (risk of bias), indirectness of evidence, serious inconsistency, imprecision of effect estimates or potential publication bias.

4. Results Final searches were carried out on the 10th January 2014. We identified 897 unique citations. Fourteen studies with 1506 participants were included. Fig. 1 provides a flow chart of the selection process. Table 1 provides a summary of the characteristics of eligible trials. Twelve studies were published. One study was submitted for publication and one study was unpublished. The earliest study was published in 2004. Twelve studies were conducted in the USA and two in Australia. Most studies recruited from community outpatient substance abuse services. Included studies were mainly of veterans or survivors of significant abuse and interpersonal violence, and included studies of males only, females only, and both genders together. 1387 (92.1%) participants met full criteria for PTSD with the remainder described as having sub-threshold PTSD. All participants met criteria for a substance use disorder. Four studies with 267 participants were of individuals with alcohol dependence or alcohol use disorder (Coffey et al., 2006; Foa et al., 2013; Norman, unpublished; Sannibale et al., 2013). The other ten studies included individuals with substance abuse, typically poly-drug use along with alcohol use disorder.

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Table 1 Characteristics of eligible randomized trials. Source (country)

Participants and setting

SUD type

Mean age

Gender

Key outcomes assessed

Experimental intervention

Control intervention

No. of participants, Treatment/control

Boden et al. (2012) (US)

Military veterans recruited from a Veterans Affairs outpatient substance use disorder clinic Laboratory based — participants recruited from outpatient SUD treatment programs Participants recruited from residential SUD treatment facility Treatment seeking participants recruited by professional referral and advertisement Participants recruited from outpatient SUD clinics

Poly drug use

54.0 (9.6)

100% male

PTSD severity; Severity of drug use

Group-based Seeking Safety + TAU

Group-based TAU

54/55

Alcohol dependence

37.5 (8.0) 33.7 (10.3)

37.5 (8.4)

Poly drug use

36.2 (9.0)

100% female


Individual trauma-focused exposure therapy Individual trauma-focused exposure therapy + TAU Individual PE + supportive counsellinga Group-based coping skill focused therapy + trauma sensitive usual care Individual Seeking Safety + TAU

Imagery-based relaxation Healthy Life Style sessions + TAU Supportive counsellinga

Poly drug use

PTSD severity; Alcohol cravings PTSD severity; Severity of alcohol use PTSD severity; Severity of alcohol use Trauma related beliefs; Severity of drug use

16/15

Alcohol dependence and poly drug use Alcohol dependence

33% male; 67% female 53.3% male; 46.7% female 65.5% male; 34.5% female 39.0% male; 61% female

Poly drug use

39.2 (9.2)

100% female


Poly drug use

37.7 (10.7)

43.4% male; 56.6% female

Substance dependent poly drug users

33.7 (7.9)

Individuals with severe mental illness were recruited from community mental health centres Outpatient adolescents recruited and from local clinics, hospitals, schools, and clinicians and through posted fliers

Poly drug use. Participants met diagnosis for SUD but not substance dependence Poly drug use. Most participants met diagnosis for substance dependence

Participants were victims of interpersonal violence recruited through flyers in community agencies serving IPV victims and in primary care and psychiatry clinics Participants were recruited from a range of services and seen on an outpatient basis Treatment was conducted on the minimum security prison. Participants were recruited from a voluntary residential substance abuse treatment program

Coffey et al. (2006) (US) Coffey et al. (submitted for publication) (US) Foa et al. (2013) (US) Frisman et al. (2008) (US)

Hien et al. (2009) (US)

McGovern et al. (2011) (US)

Mills et al. (2012) (Australia)

Mueser et al. (2008) (US)

Najavits et al. (2006) (US)

Norman, unpublished (US)

Sannibale et al. (2013) (Australia) Zlotnick et al. (2009) (US)

Out-patients recruited through substance use treatment programs and advertisement. Outpatients recruited from community-based substance abuse treatment programs Participants recruited from community intensive outpatient or methadone maintenance programs Participants recruited from substance use treatment services, advertisement and practitioner referrals

80/85

Trauma sensitive usual care

141/72

Relapse prevention + TAU

41/34b

Group-based Seeking Safety + TAU

Group-based women's health education + TAU

176/177


Individual integrated CBT for PTSD & SUD + TAU

Individual addiction counselling + TAU

32/21


PTSD severity; Severity of substance dependence

TAU

55/48

44.2 (10.6)


PTSD severity

TAU

17/27c

16.1 (1.2)

100% female

TAU

18/15

Alcohol use disorder

42.8 (9.3)

100% female

A number of measures evaluation substance abuse, trauma and SUD related cognitions and general psychopathology PTSD severity; Severity of alcohol use

Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) + TAU Individual non-trauma-focused CBT for PTSD Individual Seeking Safety + TAU

Adapted group-based Seeking Safety + treatment as usual

12-Step supportive group

20/9

Alcohol use disorder

41.2 (11.9)

47% male; 53% female

PTSD severity; Severity of alcohol use

CBT for AUD + supportive counselling

33/29

Poly drug users. 88% met criteria for alcohol dependence prior to imprisonment

34.6 (7.4)

100% female


Individual integrated trauma-focused CBT for PTSD and AUD Group-based Seeking Safety + TAU

TAU

27/22

Abbreviations: TAU, treatment as usual; PE, Prolonged Exposure. a Study used a 2 × 2 design. Participants received experimental and control psychological interventions in combination with Naltrexone or a placebo. Data were combined for the psychological intervention arms. b We did not include data from a TAU arm, as participants in this group were non-randomized. c Data were obtained for a subset of participants from this study who met inclusion criteria for the review.


Hien et al. (2004) (US)

42.7 (9.7)

82/38


Most studies excluded acute psychosis, current suicidal/homicidal ideation, and significant cognitive impairment. Some studies excluded individuals with more severe substance use difficulties, recent self-harm, involvement in a current or recent abusive relationship, advanced stage medical diseases, involvement in ongoing legal disputes, court mandated treatment, homelessness or learning disability. 4.1. Interventions All of the experimental interventions included were based on some form of CBT. 4.1.1. Individual trauma-focused approaches Five studies tested individual trauma-focused intervention, either combined with coping skills focused intervention for SUD or delivered alongside treatment as usual for SUD (Coffey et al., 2006; Coffey, Schumacher, & Nosen, submitted for publication; Foa et al., 2013; Mills et al., 2012; Sannibale et al., 2013). Coffey et al. (2006) tested an exposure-based intervention that has been established for the treatment of PTSD (Foa & Rothbaum, 1998) in participants recruited from within alcohol abuse services. They compared six sessions of imaginal exposure with six sessions of imagery-based relaxation training, with the primary aim of evaluating effects on alcohol related craving. Coffey et al. (submitted for publication) compared 9–12 sessions of imaginal and in-vivo exposure plus treatment as usual against an equivalent health related psycho-education intervention. Foa et al. (2013) tested 18 sessions of prolonged exposure plus supportive counselling against supportive counselling alone. Supportive counselling combined medication management with compliance enhancement techniques based on motivational interviewing; we took the view that this could be considered as being equivalent to a treatment as usual intervention. This was a 2 × 2 study, which also evaluated Naltrexone against a placebo. There were equal numbers of participants from the two psychological intervention groups in the two medication groups. Mills et al. (2012) compared Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) against treatment as usual. COPE includes motivational enhancement and CBT for substance use, psychoeducation relating to both disorders and their interaction, in vivo exposure, imaginal exposure, and cognitive therapy for PTSD. Finally, Sannibale et al. (2013) evaluated Integrated CBT for PTSD and AUD against CBT for AUD and supportive counselling. The experimental condition in this trial included cognitive behavioural exposure-based intervention for PTSD, based on a prolonged exposure model with cognitive restructuring, in addition to cognitive intervention for problem drinking. The control intervention had no PTSD components in it. 4.1.2. Individual non-trauma-focused approaches for PTSD and SUD Three studies evaluated individual non-trauma-focused interventions (Hien, Cohen, Miele, Litt, & Capstick, 2004; McGovern, Lambert-Harris, Alterman, Xie, & Meier, 2011; Najavits, Gallop, & Weiss, 2006). Najavits et al. (2006) compared Seeking Safety plus treatment as usual against treatment as usual. The other two studies made comparisons against alternative psychological interventions based on CBT for SUD alone. Hien et al. (2004) compared Seeking Safety plus treatment as usual to a relapse prevention comparison condition and a nonrandomised treatment as usual arm. We have not included data from this non-randomised arm in this review. McGovern et al. (2011) compared Individual CBT plus treatment as usual (ICBT) with individual addiction counselling plus treatment as usual (IAC), as the control condition. There was no PTSD component to the IAC, which at 10–12 sessions was shorter than the 12–14

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session ICBT intervention, which included psycho-education, cognitive restructuring and generalisation training in relation to PTSD and SUD. 4.1.3. Group-based non-trauma-focused approaches for PTSD and SUD Five studies evaluated group-based non-trauma-focused interventions versus treatment as usual, or treatment as usual plus a placebo experimental condition (Boden et al., 2012; Frisman, Ford, Lin, Mallon, & Chang, 2008; Hien et al., 2009; Norman, unpublished; Zlotnick, Johnson, & Najavits, 2009). Seeking Safety plus treatment as usual was the experimental intervention in four of these studies (Boden et al., 2012; Hien et al., 2004; Hien et al., 2009; Norman, unpublished). In two of these trials (Boden et al., 2012; Zlotnick et al., 2009) treatment as usual was the control condition. The intervention in Hien et al. (2009) provided a partial dose of Seeking Safety with 12 sessions, to cover the core components of the model. This study used a female health psycho-education (Women's Health Education) comparison condition, which was delivered over the same number of sessions with the same level of attention given to participants. Norman (unpublished) included some components from Cognitive Trauma Therapy for Battered Women with PTSD (CTTBW) (Kubany et al., 2004). The control condition in this study was a minimal intervention therapist led supportive 12-step group. The fifth study to evaluate a group-based integrated program was Frisman et al. (2008). This study compared TARGET, an 8–9 week intervention, which aimed to improve adaptive coping skills, with treatment as usual. 4.1.4. Individual non-trauma-focused approaches for PTSD only One further study evaluated an individual non-trauma-focused CBT based intervention for PTSD only in individuals with comorbid severe mental illness (Mueser et al., 2008). A subset of participants met diagnosis for SUD. Comparison was against treatment as usual. 4.1.5. Quality of methodology Most studies were of good methodological quality (see Appendix B), although methods used to ensure adequate allocation concealment were not always clearly described and blinding of assessors was either unclear or not undertaken in several studies. Eleven studies used an intention-to-treat analysis, although in three trials only individuals who had received at least one treatment session were included. It was unclear whether participants were aware of their allocation in two of these studies (Fergusson, Aaron, Guyatt, & Hébert, 2002). The level of drop-out was high across all studies. This was despite often modest thresholds for defining a treatment completer, only one study (Sannibale et al., 2013) reported retention of over 70%. Most studies had a completion rate of 50–70%, with one large study reporting a completion rate of only 28% for the intervention group (Frisman et al., 2008). 4.2. Assessed outcomes and evidence synthesis Outcomes were grouped and synthesised according to the intervention characteristics identified above which were decided a priori. Groupings followed guidelines of the Cochrane Collaboration (Borenstein et al., 2009; Higgins & Green, 2011). The results of meta-analyses for the main outcomes are shown in Tables 2 and 3. 4.2.1. Individual trauma-focused intervention Four studies evaluated individual trauma focused-intervention plus SUD intervention vs treatment as usual/minimal intervention (Coffey et al., 2006; Coffey et al., submitted for publication; Foa et al., 2013; Mills et al., 2012). A small effect in favour of individual trauma-focused-intervention was found for PTSD severity

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Table 2 Efficacy and tolerability of individual agents versus placebo with GRADE judgments of evidence quality. Active intervention

Individual trauma-focused CBT alongside SUD intervention

Individual non-trauma-focused intervention Individual non-trauma-focused intervention for PTSD only

Group-based non-trauma-focused intervention

PTSD severity

Drug/alcohol use

Treatment completion

Post-treatment

5–7 months post-treatment

Post-treatment


4 studies, n = 405 SMD = −0.41 (95% CI −0.72 to −0.10)a P = 0.009; I2 = 49% ⊕⊝⊝⊝ very lowb,c No data available

3 studies, n = 388 SMD = −0.33 (95% CI −0.58 to −0.10)a P = 0.006; I2 = 26% ⊕ ⊕ ⊝⊝ lowb,d No data available

3 studies, n = 388 SMD = −0.13 (95% CI −0.41 to 0.15) P = 0.35; I2 = 45% ⊕⊝⊝⊝ very lowb–d No data available

3 studies, n = 388 SMD = −0.28 (95% CI −0.48 to −0.07)a P = 0.008; I2 = 0% ⊕ ⊕ ⊝⊝ lowb,d No data available

3 studies, n = 316 RR = 0.78 (95% CI 0.64 to 0.96)a P = 0.02; I2 = 41% ⊕ ⊕ ⊝⊝ lowb,d No data available

1 study, n = 44 MD = −4.35 (95% CI −16.08 to 7.38) P = 0.47 ⊕ ⊕ ⊝⊝ lowe,f 4 studies, n = 513 SMD = −0.02 (95% CI −0.19 to 0.16) P = 0.85; I2 = 0% ⊕ ⊕ ⊝⊝ lowb,d

1 study, n = 44 MD = −4.49 (95% CI −17.78 to 8.80) P = 0.51 ⊕ ⊕ ⊝⊝ lowe,f 4 studies, n = 566 SMD = −0.14 (95% CI −0.31 to 0.03) P = 0.10; I2 = 0% ⊕⊝⊝⊝ very lowb,d,g

No data available

No data available

Data only available for the active intervention arm: 70.6% completed

3 studies, n = 464 SMD = −0.41 (95% CI −0.97 to 0.14) P = 0.15; I2 = 79% ⊕⊝⊝⊝ very lowb–d

4 studies, n = 572 SMD = −0.06 (95% CI −0.23 to 0.11) P = 0.48; I2 = 0 ⊕⊝⊝⊝ very lowb,d

2 studies, n = 381 RR = 1.13 (95% CI 0.88 to 1.45) P = 0.36; I2 = 10% ⊕ ⊕ ⊝⊝ lowb,d

GRADE Working Group grades of evidence: High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. a Statistically significant P b 0.05. b Risk of bias unclear or high in several domains. c Unexplained statistical heterogeneity. d Significant clinical heterogeneity. e Findings based on outcomes from one study with a small sample size. f Sample were individuals with severe mental illness and excluded individuals identified as having substance dependence. Therefore this cohort may not be very representative of this population. g Use of a proxy measure for PTSD in one study.

Table 3 Efficacy and tolerability of individual agents versus other active psychological intervention with GRADE judgments of evidence quality. Active intervention

Individual trauma-focused CBT alongside SUD intervention

Individual non-trauma-focused intervention

Individual non-trauma-focused intervention for PTSD only Group-based non-trauma-focused intervention

PTSD severity

Drug/alcohol use

Treatment completion

Post-treatment


Post-treatment


1 study, n = 46 MD = −3.91 (95% CI −19.16 to 11.34) P = 0.62 ⊕ ⊕ ⊝⊝ lowa 2 studies, n = 128 SMD = −0.26 (95% CI −1.29 to 0.77) P = 0.62; I2 = 87% ⊕⊝⊝⊝ very low b–d No data available

1 study, n = 45 MD = −9.32 (95% CI −22.89 to 4.25) P = 0.18 ⊕ ⊕ ⊝⊝ lowa 1 study, n = 75 MD = 7.52 (95% CI −3.78 to 18.82) P = 0.19 ⊕⊝⊝⊝ very lowb,d No data available

1 study, n = 46 MD = −1.27 (95% CI −5.76 to 3.22) P = 0.58 ⊕ ⊕ ⊝⊝ lowa 2 studies, n = 128 SMD = 0.22 (95% CI −0.13 to 0.57) P = 0.22; I2 = 0% ⊕⊝⊝⊝ very lowb,d No data available

1 study, n = 45 MD = 1.90 (95% CI −1.65 to 5.45) P = 0.29 ⊕ ⊕ ⊝⊝ lowa 1 study, n = 75 MD = 0.10 (95% CI −0.20 to 0.40) P = 0.52 ⊕⊝⊝⊝ very lowb,d No data available

1 study, n = 46 RR =1.00 (95% CI 0.74 to 1.36) P = 0.98 ⊕ ⊕ ⊝⊝ lowa 2 studies, n = 128 RR = 0.92 (95% CI 0.69 to 1.23) P = 0.58; I2 = 0% ⊕⊝⊝⊝ very lowb,d No data available

No data available

No data available

No data available

No data available

No data available

GRADE Working Group grades of evidence: High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. a Findings based on outcomes from one study with a small sample size. b Risk of bias unclear or high in several domains. c Unexplained statistical heterogeneity. d Findings based on outcomes from two studies with small sample sizes.


(SMD − 0.41; 95% CI − 0.72 to − 0.10). Effects were maintained at 3–4 months and 5–7 months of follow-up. A sensitivity analysis excluding a study that only included retained participants did not alter the finding (SMD − 0.33; 95% CI − 0.56 to − 0.10). There were no similar benefits in relation to drug/alcohol use posttreatment (SMD − 0.13; 95% CI − 0.41 to 0.15) or at 3–4 months of follow-up. However, a small effect in favour of the intervention group was identified at 5–7 months of follow-up. A significant difference in the number of treatment completers was found, in favour of retention in the control condition (RR 0.78; 95% CI 0.64 to 0.96). Using the GRADE approach the quality of evidence of these findings was graded as low to very low (see Table 2). For secondary outcomes, only Coffey et al. (submitted for publication) reported outcomes for PTSD diagnosis. There was a small treatment effect (RR 0.71; 95% CI 0.51 to 1.00) in favour of the intervention condition. Two studies (Foa et al., 2013; Mills et al., 2012) provided data on adverse events. A total of 20 events were reported in these two studies, none of which were attributed to treatment interventions provided in the studies. No significant differences in adverse event frequency were found between the two groups (RR 0.81; 95% CI 0.34 to 1.90). Data were available on the mean number of treatment sessions attended by participants in the experimental group from three studies with participants attending a mean of 6.89 (SD = 4.63) sessions. The proportions of available sessions attended per study varied from 35.2% to 68.0%. No data on diagnostic status for SUD, general functioning or use of health related resources were reported in any of these five studies. One small study (Sannibale et al., 2013) compared an individual trauma-focused intervention against another active psychological intervention in the form of CBT for SUD. There was no evidence of an effect at any time point for PTSD severity or drug/alcohol use. No data were available in this study for PTSD diagnostic status, SUD diagnostic status, adverse events, compliance, general functioning or use of health related resources. 4.2.2. Individual non-trauma-focused intervention Two studies (Hien et al., 2004; Najavits et al., 2006) evaluated Seeking Safety and the third (McGovern et al., 2011) evaluated Integrated Cognitive Behavioural Therapy (ICBT). We were unable to extract useable data from Najavits et al. (2006), which made comparison against treatment as usual for SUD. Comparisons in the other two studies were made against other active psychological interventions for SUD only. These were relapse prevention for Hien et al. (2004) and a similar individual addiction counselling approach for McGovern et al. (2011). In comparing individual non-traumafocused intervention with other active psychological interventions we found no benefit for PTSD severity or drug/alcohol use posttreatment (SMD − 0.26; 95% CI − 1.29 to 0.77 and SMD 0.13; 95% CI − 0.22 to 0.49 respectively) or at 3–4 or 5–7 months of followup and no difference on rate of treatment completion. Using the GRADE approach the quality of evidence of these findings was graded as very low (see Table 3). For secondary outcomes, data on PTSD diagnosis were available from one study post-treatment. No difference was found between the two groups (n = 75; RR 0.94; 95% CI 0.68 to 1.30). Data from this study were also available for treatment compliance. There were no differences between the two groups for treatment attendance (n = 75; MD − 0.10; 95% CI − 3.75 to 3.55); with attendance of 48.0% at the experimental group sessions and 48.4% at the control group sessions. No data were available for SUD diagnostic status, adverse events, general functioning or use of health related resources. We note that there are differences between the interventions provided in Seeking Safety and ICBT. In particular, cognitive restructuring is a significant component of ICBT. We

33

also note that McGovern et al. (2011) reported significant improvements in PTSD re-experiencing (but not overall PTSD severity) and PTSD diagnosis for ICBT over individual addiction counselling. 4.2.3. Group-based non-trauma-focused intervention Four studies (Boden et al., 2012; Hien et al., 2009; Norman, unpublished; Zlotnick et al., 2009) evaluated Seeking Safety with a fifth study (Frisman et al., 2008) also evaluating a program based on a CBT approach to developing adaptive coping skills. Hien et al., (2009) delivered a partial dose of 12 key sessions of Seeking Safety, instead of the standard 25 sessions. All comparisons were against treatment as usual/minimal intervention. For PTSD severity and drug/alcohol use there was no evidence of an effect post-treatment (SMD − 0.02; 95% CI − 0.19 to 0.16 and SMD − 0.41; 95% CI − 0.97 to 0.14 respectively), at 3–4 months of follow-up, 5–7 months of follow-up or 12 months of follow-up. Post hoc analyses including only data from the full dose Seeking Safety studies showed no effect on PTSD symptoms. There was an effect on drug/alcohol post-treatment (k = 2; n = 111; SMD − 0.67; 95% CI − 1.14 to − 0.19) but not at later follow-up. Data were available on the number of treatment completers for Hien et al. (2009) and Norman (unpublished). There was no evidence of any significant difference in drop-out rate between the two conditions (RR 1.13; 95% CI 0.88 to 1.45). Using the GRADE approach the quality of evidence of these findings was graded as low to very low (see Table 2). For secondary outcomes, Norman (unpublished) and Zlotnick et al. (2009) provided data on PTSD diagnostic status post treatment. There was no evidence of an effect (n = 77; RR 1.01; 95% CI 0.66 to 1.54). Boden et al. (2012), Hien et al. (2009) and Norman (unpublished) reported on adverse events. No adverse events were reported in Boden et al. (2012) and Norman (unpublished). Hien et al. (2009) reported 83 study related adverse events from 353 participants (reported in Killeen et al., 2008). No differences were found in the number of events experienced between the two conditions (RR 1.13; 95% CI 0.88 to 1.45). Data were available on the mean number of treatment sessions attended by participants in the experimental group from all five studies with participants attending a mean of 6.31 (SD = 5.71) sessions. The proportion of available sessions attended for the experimental group per study varied from 37.9% to 62.4%. No data were available for other secondary outcomes. It is relevant to note that participant attendance for Hien et al. (2009) has been subject to further secondary analysis (Hien et al., 2012). This analysis identified three patterns of attendance: “completers” attending 80% or more of sessions, “droppers” attending 41% or less of sessions), and “titrators” with 50% to 80% attendance. Hien et al. (2012) presented data that suggested significant improvements for substance abuse outcomes for “titrators” who attended Seeking Safety over the control condition. 4.2.4. Individual non-trauma-focused intervention for PTSD only Data were available from one study (Mueser et al., 2008) that evaluated an intervention for PTSD only, against treatment as usual in patients with serious mental illness. We found no evidence of effect post-treatment, at 3–4 months or at 5–7 months for a sub-group who also met diagnosis for SUD. Data on treatment adherence were available only for participants receiving the experimental intervention: 70.6% of participants attended a minimum of 6 of the 16 available treatment sessions and were considered as treatment completers; 52.9% attended 12 or more sessions. 5. Conclusion We included 14 RCTs with 1506 participants in this review. These studies evaluated several broad types of intervention. We

34


found evidence to suggest that psychological intervention that includes a trauma-focused component alongside intervention for SUD can help reduce PTSD symptom severity for individuals with PTSD and co-morbid SUD. These results need to be interpreted with caution. Treatment effects were small and mostly for PTSD. The finding that participants allocated to receive trauma-focused intervention were less likely to complete treatment suggests possible tolerability issues. Participants in the studies included in this review are likely to have received a range of other stabilizing interventions alongside traumafocused treatment and we found no evidence to support the delivery of trauma-focused interventions alone. We found little evidence to support the use of non-trauma-focused group-based interventions. Individual non-trauma-focused interventions have not been widely evaluated. We found no strong evidence for such interventions, although some positive indications were reported for integrated cognitive behavioural therapy (McGovern et al., 2011). Treatment drop-out was high across all studies, regardless of intervention type and this is clearly a major challenge in trying to help individuals with PTSD and co-morbid SUD (Foa & Williams, 2010; Schäfer & Najavits, 2007). Clinicians will want to exercise caution in deciding whether to provide interventions identified in this review (Cloitre et al., 2011; Najavits & Hien, 2013). Individuals with more severe and complex presentations (such as those with other serious mental illness, individuals with cognitive impairment and individuals who are suicidal) were excluded from most studies and it would be inappropriate to generalise our findings to such individuals. The quality of evidence described in this review was assessed as being of low to very low quality and findings may be liable to change as further evidence is accumulated. The findings may, therefore, be best regarded as preliminary. This is the first systematic review of psychological interventions for PTSD and SUD that we are aware of to be based only on RCTs. Other systematic reviews have based their conclusions on findings from both controlled and non-controlled studies (Torchalla et al., 2012; van Dam et al., 2012). This review substantially builds on the previous reviews, for example by including 8 (133%) more RCTs than were included by van Dam et al. (2012), and will allow clinical decisions to be informed by a more robust evidence base. In common with van Dam et al. (2012), we found that the most promising outcome data, albeit with small treatment effects, are for psychosocial interventions that incorporate trauma-focused intervention alongside intervention for SUD. This finding of a small effect is consistent with the findings from a recent meta-analysis (Gerger et al., 2014). This meta-analysis also found that the benefits of specific traumafocused interventions were small in studies with participants with more complex clinical problems. Our findings that fewer individuals assigned to trauma-focused intervention than control condition completed treatment is consistent with findings from the recent Cochrane Review of psychological interventions for chronic PTSD (Bisson et al., 2013; Lewis, Roberts, Andrew, Cooper, & Bisson, submitted for publication), suggesting that such interventions may not always be well tolerated. Despite data on medium to long-term follow-up from some studies, follow-up rates were low and true follow-up effects relied heavily on estimation through ITT; this may have resulted in the outcomes reported being too conservative or too optimistic of true effects. Several studies only reported data for participants who were available to follow-up (Coffey et al., 2006; McGovern et al., 2011; Zlotnick et al., 2009), and in some analyses this data was used in conjunction with ITT data from other studies. Sensitivity analyses excluding these studies made no difference to our findings.

On first sight, our findings in favour of trauma-focused intervention might appear to be at odds with the findings of two of the studies included in this comparison (Foa et al., 2013; Mills et al., 2012). Foa et al. (2013) found no improvement in PTSD symptoms for trauma-focused CBT over the control condition and Mills et al. (2012) only found benefits for trauma-focused CBT at their final follow-up. Positive findings for trauma-focused CBT were identified because meta-analysis increases statistical power which makes it easier to detect “nonzero” effects (Cohn & Becker, 2003). As previously noted these effects were small. In addition to estimating a common effect, another goal of meta-analysis is to assess dispersion (Borenstein et al., 2009). There were too few studies in the traumafocused intervention comparison to undertake sensitivity analysis. We note, however, that for the outcome of PTSD severity, participants in Coffey et al. (submitted for publication) showed the greatest improvement compared to the control condition of all studies included in this review. This study used an adapted form of traumafocused CBT with shorter exposure sessions. As further evidence accumulates, researchers will be able to investigate these differences further. There was a high level of clinical heterogeneity in the included studies. Clinical populations were diverse in terms of type of trauma exposure, nature of and severity of substance abuse and dependence. Meta-analysis only rarely involves synthesis of data from identical studies (Borenstein et al., 2009). We attempted to group studies together in a way that was logical and clinically meaningful based on criteria that we identified a priori. However, interventions differed in terms of session content, number of sessions, session length, and the nature of additional substance use intervention. The substance use intervention was integral to the active intervention in some studies, but from a separate source in other studies. Treatment as usual also varied across studies, and often contained some form of psychological intervention. There was notable statistical heterogeneity in some analyses but we were only able to undertake limited investigation of factors potentially contributing to this, due to the limited number of studies included. The majority of the studies that we identified compared an active psychological intervention against treatment as usual, or minimal intervention conditions. The studies comparing active psychological intervention against other psychological intervention tended to be small; this may mean that we were unable to identify effects that would be more apparent in studies that are better powered. Our review employed stringent methodology, and addressed many of the issues raised by van Dam et al. (2012), but has some limitations. We undertook a robust search strategy, identified a number of unpublished studies from conference abstracts, and made efforts to contact study authors where possible. We were able to include data from one unpublished study (Norman, unpublished), but it is possible that there are other unpublished studies that we have missed. We mainly contacted research groups in English speaking countries and elsewhere in Europe, and a significant number of authors did not respond. We did not identify any relevant research groups outside of these areas of the world. We included data from one study that did not specifically provide interventions to treat PTSD/SUD co-morbidity but included a significant minority of individuals who met diagnosis (Mueser et al., 2008). We included this study on the basis that it met our a priori specified inclusion criteria and may provide evidence about how individuals with PTSD/SUD co-morbidity respond to such non-specific intervention. This study only included individuals with severe mental illness. It would, therefore, be inappropriate to generalise these findings beyond a severely mentally ill population. We also approached authors of several other studies where a minority of participants may have met our criteria but we were not able to obtain subset data from these studies. We


reported some significant findings for treatment completion/dropout. These findings were based on study definitions of what constituted a treatment completer. These definitions varied greatly across studies. It was not possible to compile data around more unified definitions but it is possible that this effect would not have been apparent, or have been more pronounced, if the studies included were more consistent about their definitions of treatment completers. Despite advances in the evidence base, further well-designed trials are clearly required (van Dam et al., 2012). There is a need to replicate findings in support of trauma-focused intervention and to identify optimal modes of intervention delivery and factors influencing treatment retention (Ouimette & Brownl, 2003; Pinto, Campbell, Hien, & Yu, 2011). We have identified high treatment drop-out as an area of concern across treatment approaches. However, as Hien et al. (2012) note, the relationship between treatment attendance and outcome is not necessarily a linear one and self-directed treatment titration may be beneficial for those with comorbidity. This should be investigated further. Non-trauma-focused interventions for individuals have not been widely studied and should be evaluated further. Most of the studies in this review recruited participants from substance misuse services and/or provided supplementary SUD related interventions, which were equivalent across treatment arms. There is little evidence about treatment effects when SUD related intervention is minimal. Future studies should examine whether this is an essential component of treatment. There is some evidence to suggest that outcomes may be improved when psychological intervention is delivered in combination with pharmacological intervention for this patient group; this also warrants further investigation (Foa et al., 2013). Finally, individuals with PTSD and co-morbid SUD often require interventions from different services and there is a need to evaluate optimal treatment pathways. Role of funding sources This study was not directly funded but was undertaken whilst Dr N. Roberts was in receipt of a National Institute of Social Care and Health Research — Academic Health Science Committee (NISCHR AHSC) Clinical Research Fellowship and was supported by the Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine and Cardiff & Vale University Health Board. These organizations had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication.

Author contributions Drs N. Roberts, P. Roberts and Bisson designed the study and wrote the protocol. Drs N. Roberts, P. Roberts and Jones conducted literature searches and acquisition of data. Drs N. Roberts and Bisson conducted the statistical analysis. Dr N. Roberts wrote the first draft of the manuscript and all authors contributed to and have approved the final manuscript. Conflict of interest None of the authors have any conflicts of interest to disclose.

Acknowledgements With thanks to the editorial team of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDAN). Thanks also to Dr Kim Mueser, Dr Scott Coffey, Dr Katherine Mills, Dr Denise Hien and Dr Sonya Norman for additional data. We would like to thank Dr Lisa Najavits for feedback on an earlier draft of the review.

Appendix A Predefined search strategy Electronic searches We conducted a search for Condition (PTSD) and Population (patients with comorbid substance abuse). 1. CCDANCTR-Studies Register

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We searched the studies register using the following terms: Condition = ("post-traumatic stress disorders") AND Comorbidity = ("alcohol dependence" or "substance related disorders" or "substance abuse") 2. CCDANCTR-References Register We searched the references register using a more sensitive set of freetext terms: [Condition] 1. (PTSD or post-trauma* or "post trauma*" or posttrauma* or "stress disorder*" or "combat disorder*" or "war neuros*") 2. (trauma* and (psycho* or stress*)) 3. (stress* and (extreme or disorder*)) 4. DESNOS 5. (1 or 2 or 3 or 4) [Population: comorbid substance abuse] 6. ("substance use disorder*" or SUD) 7. "drug abuse" 8. (abuser* or abusing or addict* or depend* or habit* or misuse or user*) 9. (abuse and not (child* or sex*)) [Common drugs of abuse] 10. (adinazolam or aerosol* or alcohol* or alprazolam or amphetamin* or anthramycin or anxiolytic* or ativan or barbituat* or bentazepam or benzodiazepin* or bromazepan or brotizolam or buprenorphin* or camazepam or cannabi* or chlordiazepoxid* or cinolazepam or clobazam or clonazepam or clorazepam or clotiazepam or cloxazolam or cocaine* or codeine or crack or crystal or cyprazepam or depressant* or diacetylmorphin* or diazepam* or doxefazepam or ecstasy or estazolam or etizolam or fentanyl or flunitrazepam or flurazepam or flutazoram or flutoprazepam or fosazepam or gases or GHB or girisopam or halazepam or hallucinogen* or haloxazepam or heroin* or hydromorphone or hydroquinone or hypnotic* or inhalant* or ketamin* or ketazolam or librium or loflazepate or loprazolam or lorazepam or lormetazepam or LSD or marihuana* or marijuana* or MDMA or meclonazepam or medazepam or meperidine or mephedrone or mescalin* or metaclazepam or methadone or methamphetamin* or methaqualone or mexazolam or midazepam or midazolam or morphine* or narcotic* or nerisopam or nimetazepam or nitrazepam or nitrites or "nitrous oxide" or "n-methyl-3,4-methylenedioxyamphetamine" or nordazepam or opiate* or opiod* or opium or oxazepam or oxazolam or oxazypam or oxycodone or oxzepam or painkiller* or "pain killer*" or PCP or pethidin* or phencyclidin* or pinasepam or prazepam or propazepam or propoxyphene or psilocybin or psychedelic* or psychoactive* or psychostimulant* or quinazolinone or ripazepam or ritalin or sedative* or serazepin* or solvent* or steroid* or stimulant* or substance* or temazepam or tetrazepam or tofisopam or tramadol or triazolam or triflubazam or valium or vicodin) 11. (drug* and (recreational or street)) 12. (6 or 7 or 8 or 9 or 10 or 11) [Condition + Population] 13. (5 and 12) 3. CENTRAL We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) 4. International Trial Registries We searched the World Health Organization's Trials portal (ICTRP) and ClinicalTrials.gov to identify additional unpublished or ongoing studies.

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Appendix B. Study characteristics related to the risk of bias


References Back, S. E., Dansky, B. S., Carroll, K. M., Foa, E. B., & Brady, K. T. (2001). Exposure therapy in the treatment of PTSD among cocaine-dependent individuals: Description of procedures. Journal of Substance Abuse Treatment, 21, 35–45. http://dx.doi.org/10.1016/ S0740-5472(01)00181-7. Berenz, E. C., & Coffey, S. F. (2012). Treatment of co-occurring posttraumatic stress disorder and substance use disorders. Current Psychiatry Reports, 14(5), 469–477. http:// dx.doi.org/10.1007/s11920-012-0300-0. Bisson, J. I., Roberts, N. P., Andrew, M., Cooper, R., & Lewis, C. (2013). Psychological therapies for chronic post-traumatic stress disorder (PTSD) in adults. Cochrane Database of Systematic Reviews(Issue 12). http://dx.doi.org/10.1002/14651858.CD003388. pub4 (Art. No.: CD003388). Boden, M. T., Kimerling, R., Jacobs-Lentz, J., Bowman, D., Weaver, C., Carney, D., et al. (2012). Seeking Safety treatment for male veterans with a substance use disorder and post-traumatic stress disorder symptomatology. Addiction, 107(3), 578–586. http://dx.doi.org/10.1111/j.1360-0443.2011.03658.x. Boden, M. T., Kimerling, R., Kulkarni, M., Bonn-Miller, M. O., Weaver, C., & Trafton, J. (2014). Coping among military veterans with PTSD in substance use disorder treatment. Journal of Substance Abuse Treatment, 47, 160–167. http://dx.doi.org/10.1016/ j.jsat.2014.03.006. Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2009). Introduction to Meta-Analysis. New York: John Wiley & Sons. Bradley, R., Greene, J., Russ, E., Dutra, L., & Westen, D. (2005). A multidimensional metaanalysis of psychotherapy for PTSD. American Journal of Psychiatry, 162, 214–227. http://dx.doi.org/10.1176/appi.ajp.162.2.214. Breslau, N., & Davis, G. C. (1992). Posttraumatic stress disorder in an urban population of young adults: Risk factors for chronicity. American Journal of Psychiatry, 149, 671–675. http://dx.doi.org/10.1176/ajp.149.5.671. Brown, P. J., Read, J. P., & Kahler, C. W. (2003). Comorbid posttraumatic stress disorder and substance use disorders: Treatment outcomes and the role of coping. In P. Ouimette, & P. J. Brown (Eds.), Trauma and substance abuse: Causes, consequences and treatment of comorbid disorders (pp. 171–188). Washington DC: American Psychological Association. Busuttil, W. (2009). Complex PTSD: A useful diagnostic frame work? Psychiatry, 8(8), 310–314. http://dx.doi.org/10.1016/j.mppsy.2009.04.014. Cloitre, M., Courtois, C. A., Charuvastra, A., Carapezza, R., Stolbach, B. C., & Green, B. L. (2011). Treatment of complex PTSD: Results of the ISTSS expert clinician survey on best practices. Journal of Traumatic Stress, 24(6), 615–627. http://dx.doi.org/10. 1002/jts.20697. Cloitre, M., Miranda, R., StovalI-McCIough, C., & Han, H. (2005). Beyond PTSD: Emotion regulation and interpersonal problems predictors of functional impairment in survivors of childhood abuse. Behavior Therapy, 36, 119–124. http://dx.doi.org/10.1016/ S0005-7894(05)80060-7. Coffey, S. F., Schumacher, J. A., & Nosen, E. (2015n). Trauma-focused exposure therapy for chronic posttraumatic stress disorder in alcohol and drug dependent patients: A randomized clinical trial. (submitted for publication). Coffey, S. F., Stasiewicz, P. R., Hughes, P. M., & Brimo, M. L. (2006). Trauma-focused imaginal exposure for individuals with comorbid posttraumatic stress disorder and alcohol dependence: Revealing mechanisms of alcohol craving in a cue reactivity paradigm. Psychology of Addictive Behaviors, 20(4), 425–435. http://dx.doi.org/10. 1037/0893-164X.20.4.425. Cohn, L. D., & Becker, B. J. (2003). How meta-analysis increases statistical power. Psychological Methods, 8(3), 243–253. http://dx.doi.org/10.1037/1082-989X.8.3.243. Dragan, M., & Lis-Turlejska, M. (2007). Prevalence of posttraumatic stress disorder in alcohol dependent patients in Poland. Addictive Behaviors, 32, 902–911. http://dx. doi.org/10.1016/j.addbeh.2006.06.025. Driessen, M., Schulte, S., Luedecke, C., Schaefer, I., Sutmann, F., & Ohlmeier, M. (2008). Trauma and PTSD in patients with alcohol, drug, or dual dependence: A multi-center study. Alcoholism: Clinical and Experimental Research, 32(3), 481–488. http://dx.doi.org/10. 1111/j.1530-0277.2007.00591.x. Ehlers, A., & Clark, D. M. (2000). A cognitive model of posttraumatic stress disorder. Behaviour Research and Therapy, 38(4), 319–345. http://dx.doi.org/10.1016/S00057967(99)00123-0. Ehring, T., & Quack, D. (2010). Emotion regulation difficulties in trauma survivors: The role of trauma type and PTSD symptom severity. Behavior Therapy, 41, 587–598. http://dx.doi.org/10.1016/j.beth.2010.04.004. Ehring, T., Welboren, R., Morina, N., Wicherts, J. M., Freitag, J., & Emmelkamp, P. M. (2014). Meta-analysis of psychological treatments for posttraumatic stress disorder in adult survivors of childhood abuse. Clinical Psychology Review, 34(8), 645–657. http://dx. doi.org/10.1016/j.cpr.2014.10.004. Fergusson, D., Aaron, S. D., Guyatt, G., & Hébert, P. (2002). Post randomisation exclusions: The intention to treat principle and excluding patients from analysis. British Medical Journal, 325, 652–654. http://dx.doi.org/10.1136/bmj.325.7365.0/f. Foa, E. B., & Rothbaum, B. O. (1998). Treating the trauma of rape: Cognitive behavioral therapy for PTSD. New York: Guilford Press. Foa, E. B., & Williams, M. T. (2010). Methodology of a randomized double-blind clinical trial for comorbid posttraumatic stress disorder and alcohol dependence. Mental Health and Substance Use, 3(2), 131–147. http://dx.doi.org/10.1080/17523281003738661. Foa, E. B., Yusko, D. A., McLean, C. P., Suvak, M. K., Bux, D. A., Oslin, D., et al. (2013). Concurrent Naltrexone and prolonged exposure therapy for patients with comorbid alcohol dependence and PTSD: A randomized clinical trial. Journal of the American Medical Association, 310(5), 488–495. http://dx.doi.org/10.1001/jama.2013.8268. Ford, J. D., Hawke, J., Alessi, S., Ledgerwood, D., & Petry, N. (2007). Psychological trauma and PTSD symptoms as predictors of substance dependence treatment outcomes. Behaviour Research and Therapy, 45(10), 2417–2431. http://dx.doi.org/10.1016/j. brat.2007.04.001.

37

Frisman, L., Ford, J., Lin, H. -J., Mallon, S., & Chang, R. (2008). Outcomes of trauma treatment using the TARGET model. Journal of Groups in Addiction & Recovery, 3(3–4), 285–303. http://dx.doi.org/10.1080/15560350802424910. Gerger, H., Munder, T., & Barth, J. (2014). Specific and nonspecific psychological interventions for PTSD symptoms: A meta-analysis with problem complexity as a moderator. Journal of Clinical Psychology, 70(7), 601–615. http://dx.doi.org/10.1002/jclp.22059. Guyatt, G. H., Oxman, A. D., Schünemann, H. J., Tugwell, P., & Knottnerus, A. (2011). GRADE guidelines: A series of new articles in the Journal of Clinical Epidemiology. Journal of Clinical Epidemiology, 64(4), 380–382. http://dx.doi.org/10.1016/j.jclinepi.2010.09.011. Guyatt, G. H., Oxman, A. D., Sultan, S., Brozek, J., Glasziou, P., et al. (2013). GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. Journal of Clinical Epidemiology, 66, 151–157. http://dx. doi.org/10.1016/j.jclinepi.2012.01.006. Hedges, L. V. (1981). Distribution theory for Glass's estimator of effect size and related estimators. Journal of Educational and Behavioral Statistics, 6, 107–128. http://dx.doi.org/ 10.3102/10769986006002107. Hien, D. A., Cohen, L. R., Miele, G. M., Litt, L. C., & Capstick, C. (2004). Promising treatments for women with comorbid PTSD and substance use disorders. American Journal of Psychiatry, 161(8), 1426–1432. http://dx.doi.org/10.1176/appi.ajp.161.8.1426. Hien, D. A., Morgan-Lopez, A. A., Campbell, A. N., Saavedra, L. M., Wu, E., Cohen, L., et al. (2012). Attendance and substance use outcomes for the Seeking Safety program: Sometimes less is more. Journal of Consulting and Clinical Psychology, 80(1), 29–42. http://dx.doi.org/10.1037/a0026361. Hien, D. A., Wells, E. A., Jiang, H., Suarez-Morales, L., Campbell, A. N. C., Cohen, L. R., et al. (2009). Multisite randomized trial of behavioral interventions for women with cooccurring PTSD and substance use disorders. Journal of Consulting and Clinical Psychology, 77(4), 607–619. http://dx.doi.org/10.1037/a0016227. Higgins, J. P. T., & Green, S. (Eds.). (2011). Cochrane handbook for systematic reviews of interventions: Version 5.3.5. The Cochrane Collaboration (available from www. cochrane-handbook.org). Hruska, B., Fallon, W., Spoonster, E., Sledjeski, E. M., & Delahanty, D. L. (2011). Alcohol use disorder history moderates the relationship between avoidance coping and posttraumatic stress symptoms. Psychology of Addictive Behaviors, 25(3), 405–414. http://dx. doi.org/10.1037/a0022439. Jacobsen, L. K., Southwick, S. M., & Kosten, T. R. (2001). Substance use disorders in patients with posttraumatic stress disorder: A review of the literature. American Journal of Psychiatry, 158(8), 1184–1190. http://dx.doi.org/10.1176/appi.ajp.158.8.1184. Keane, T. M., & Wolfe, J. (1990). Comorbidity in post-traumatic stress disorder: An analysis of community and clinical studies. Journal of Applied Social Psychology, 20, 1776–1788. http://dx.doi.org/10.1111/j.1559-1816.1990.tb01511.x. Kessler, R. C., Sonnega, A., Bromet, E., Hughes, M., & Nelson, C. B. (1995). Posttraumatic stress disorder in the National Comorbidity Survey. Archives of General Psychiatry, 52(12), 1048–1060. http://dx.doi.org/10.1001/archpsyc.1995.03950240066012. Khantzian, E. J. (1985). The self-medication hypothesis of addictive disorders: Focus on heroin and cocaine dependence. The American Journal of Psychiatry, 142(11), 1259–1264. http://dx.doi.org/10.1176/ajp.142.11.1259. Killeen, T., Hien, D., Campbell, A., Brown, C., Hansen, C., Jiang, H., et al. (2008). Adverse events in an integrated trauma-focused intervention for women in community substance abuse treatment. Journal of Substance Abuse Treatment, 35(3), 304–311. http://dx.doi.org/10.1016/j.jsat.2007.12.001. Kline, A., Weiner, M. D., Ciccone, D. S., Interian, A., St Hill, L., & Losonczy, M. (2014). Increased risk of alcohol dependency in a cohort of National Guard troops with PTSD: A longitudinal study. Journal of Psychiatric Research, 50, 18–25. http://dx.doi.org/10. 1016/j.jpsychires.2013.11.007. Knapp, W. P., Soares, B., Farrell, M., & Silva de Lima, M. (2007). Psychosocial interventions for cocaine and psychostimulant amphetamines related disorders. Cochrane Database of Systematic Reviews(Issue 3). http://dx.doi.org/10.1002/14651858.CD003023.pub2 (Art. No.: CD003023). Kober, H. (2014). Emotion regulation in substance use disorders. In J. Gross (Ed.), Handbook of emotion regulation (2nd Edition ). Guilford: New York, NY. Krueger, R. F., & Markon, K. E. (2006). Reinterpreting comorbidity: A model-based approach to understanding and classifying psychopathology. Annual Review of Clinical Psychology, 2, 111–133. http://dx.doi.org/10.1111/j.0963-7214.2006.00418.x. Kubany, E. S., Hill, E. E., Owens, J. A., Iannce-Spencer, C., McCaig, M. A., Tremayne, K. J., et al. (2004). Cognitive trauma therapy for battered women with PTSD (CTT-BW). Kulka, R. A., Schlenger, W. E., Fairbank, J. A., Hough, R. L., Jordan, B. K., Marmar, C. R., et al. (1990). Trauma and the Vietnam war generation: Report of findings from the National Vietnam Veterans Readjustment Study. New York: Bruner/Mazel. Langendam, M. W., Akl, E. A., Dahm, P., Glasziou, P., Guyatt, G., & Schünemann, H. J. (2013). Assessing and presenting summaries of evidence in Cochrane Reviews. Systematic Reviews, 23(2), 81. http://dx.doi.org/10.1186/2046-4053-2-81. Lewis, C., Roberts, N. P., Andrew, M., Cooper, R., & Bisson, J. I. (2015n). Drop-out from psychological therapy for post-traumatic stress disorder: A systematic review and metaanalysis. (submitted for publication). Mayet, S., Farrell, M., Ferri, M., Amato, L., & Davoli, M. (2004). Psychosocial treatment for opiate abuse and dependence. Cochrane Database of Systematic Reviews(Issue 4). http://dx.doi.org/10.1002/14651858.CD004330.pub2 (Art. No.: CD004330). McDermott, M. J., Tull, M. T., Gratz, K. L., Daughters, S. B., & Lejuez, C. W. (2009). The role of anxiety sensitivity and difficulties in emotion regulation in posttraumatic stress disorder among crack/cocaine dependent patients in residential substance abuse treatment. Journal of Anxiety Disorders, 23, 591–599. http://dx.doi.org/10.1016/j. janxdis.2009.01.006. McDevitt-Murphy, M. E., Williams, J. L., Bracken, K. L., Fields, J. A., Monahan, C. J., & Murphy, J. G. (2010). PTSD symptoms, hazardous drinking, and health functioning among U.S. OEF and OIF veterans presenting to primary care. Journal of Traumatic Stress, 23(1), 108–111. http://dx.doi.org/10.1002/jts.20482.

38


McGovern, M. P., Lambert-Harris, C., Alterman, A. I., Xie, H., & Meier, A. (2011). A randomized controlled trial comparing integrated cognitive behavioral therapy versus individual addiction counseling for co-occurring substance use and posttraumatic stress disorders. Journal of Dual Diagnosis, 7(4), 207–227. http://dx.doi.org/10.1080/ 15504263.2011.620425. Meyer, R. E. (1986). How to understand the relationship between psychopathology and addictive disorders: Another example of the chicken and the egg. In R. E. Meyer (Ed.), Psychopathology and Addictive Disorders. New York: Guilford Press. Mills, K. L., Teeson, M., Back, S. E., Brady, K. T., Baker, A. L., Hopwood, S., et al. (2012). Integrated exposure based therapy for co-occurring posttraumatic stress disorder and substance dependence. Journal of the American Medical Association, 308(7), 690–699. http://dx.doi.org/10.1001/jama.2012.9071. Mills, K. L., Teeson, M., Ross, J., & Peters, L. (2006). Trauma, PTSD, and substance use disorders: Findings from the Australian National Survey of Mental Health and WellBeing. American Journal of Psychiatry, 163(4), 651–658. http://dx.doi.org/10.1176/ appi.ajp.163.4.652. Moos, R. H. (2007). Theory-based active ingredients of effective treatments for substance use disorders. Drug and Alcohol Dependence, 88, 109–121. http://dx.doi.org/10.1016/j. drugalcdep.2006.10.010. Mueser, K. T., Rosenburg, S. D., Xie, H., Jankowski, M. K., Bolton, E. E., Lu, W., et al. (2008). A randomized controlled trial of cognitive–behavioral treatment for posttraumatic stress disorder in severe mental illness. Journal of Consulting and Clinical Psychology, 76(2), 259–271. http://dx.doi.org/10.1037/0022-006X.76.2.259. Najavits, L. M. (2002). Seeking Safety. A treatment manual for PTSD and substance abuse. New York: Guilford Press. Najavits, L. M. (2006). Seeking Safety. In V. Follette, & J. L. Ruzek (Eds.), Cognitive–behavioral therapies for trauma (pp. 228–257) (2nd Ed.). New York: Guilford Press. Najavits, L. M., Gallop, R. J., & Weiss, R. D. (2006). Seeking Safety therapy for adolescent girls with PTSD and substance use disorder: A randomized controlled trial. Journal of Behavioral Health Services and Research, 33(4), 453–463. http://dx.doi.org/10. 1007/s11414-006-9034-2. Najavits, L. M., & Hien, D. (2013). Helping vulnerable populations: A comprehensive review of the treatment outcome literature on substance use disorder and PTSD. Journal of Clinical Psychology, 69(5), 433–479. http://dx.doi.org/10.1002/jclp.21980. Norman S. (unpublished). Alcohol Use Disorders (AUDs) and Post-traumatic Stress Disorder (PTSD) Treatment for Victims of Partner Violence. Clinical Trials Unpublished. http://clinicaltrials.gov/ct2/show/NCT00607412 2007 Ouimette, P., & Brown, P. J. (2003). Epiolgue: Future Directions. In P. Ouimette, & P. J. Brown (Eds.), Trauma and substance abuse: Causes, consequences, and treatment of comorbid disorders (pp. 243–245). Washington DC: American Psychological Association. Ouimette, P., Moos, R. H., & Brown, P. J. (2003). Substance use disorder-posttraumatic stress disorder comorbidity: A survey of treatments and proposed practice guidelines. In P. Ouimette, & P. J. Brown (Eds.), Trauma and substance abuse: Causes, consequences, and treatment of comorbid disorders (pp. 91–110). Washington DC: American Psychological Association. Ouimette, P., Moos, R. H., & Finney, J. W. (2003). PTSD treatment and 5-year remission among patients with substance use and posttraumatic stress disorders. Journal of Consulting and Clinical Psychology, 71(2), 410–414. http://dx.doi.org/10.1037/0022006X.71.2.410. Pietrzak, R. H., Goldstein, R. B., Southwick, S. M., & Grant, B. F. (2011). Prevalence and axis I comorbidity of full and partial posttraumatic stress disorder in the United States: Results from wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Journal of Anxiety Disorders, 25(3), 456–465. http://dx.doi.org/10.1016/j. janxdis.2010.11.010. Pineles, S. L., Mostoufi, S. M., Ready, C. B., Street, A. E., Griffin, M. G., & Resick, P. A. (2011). Trauma reactivity, avoidant coping, and PTSD Symptoms: A moderating relationship? Journal of Abnormal Psychology, 120(1), 240–246. http://dx.doi.org/10.1037/a0022123. Pinto, R. M., Campbell, A. N. C., Hien, D. A., & Yu, G. (2011). Retention in the National Institute on Drug Abuse Clinical Trials. American Journal of Orthopsychiatry, 81(2), 211–217. http://dx.doi.org/10.1111/j.1939-0025.2011.01090.x. Powers, M. B., Vedel, E., & Emmelkamp, P. M. G. (2008). Behavioral couples therapy (BCT) for alcohol and drug use disorders: A meta-analysis. Clinical Psychology Review, 28, 952–962. http://dx.doi.org/10.1016/j.cpr.2008.02.002.

Resick, P. A., & Schnicke, M. K. (1993). Cognitive processing therapy for rape victims: A treatment manual. Newbury Park, CA: Sage. Review Manager (RevMan) Version 5.3.5 (2011). [Computer program]. Copenhagen: The Nordic Cochrane Centre. The Cochrane Collaboration (http://tech.cochrane.org/ revman/download). Reynolds, M., Hinchliffe, K., Asamoah, V., & Kouimtsidis, C. (2011). Trauma and posttraumatic stress disorder in a drug treatment community service. Psychiatric Bulletin, 35, 256–260. http://dx.doi.org/10.1192/pb.bp.110.030379. Reynolds, M., Mezey, G., Chapman, M., Wheeler, M., Drummond, C., & Baldacchino, A. (2005). Co-morbid post-traumatic stress disorder in a substance misusing clinical population. Drug and Alcohol Dependence, 77(3), 251–258. http://dx.doi.org/10. 1016/j.drugalcdep.2004.08.017. Sannibale, C., Teesson, M., Creamer, M., Sitharthan, T., Bryant, R. A., Sutherland, K., et al. (2013). Randomized controlled trial of cognitive behaviour therapy for comorbid post-traumatic stress disorder and alcohol use disorders. Addiction, 108(8), 1397–1410. http://dx.doi.org/10.1111/add.12167. Schäfer, I., Langeland, W., Hissbach, J., Luedecke, C., Ohlmeier, M. D., Chodzinski, C., et al. (2010). Childhood trauma and dissociation in patients with alcohol dependence, drug dependence, or both — a multi-center study. Drug and Alcohol Dependence, 109, 84–89. http://dx.doi.org/10.1016/j.drugalcdep.2009.12.012. Schäfer, I., & Najavits, L. M. (2007). Clinical challenges in the treatment of patients with posttraumatic stress disorder and substance abuse. Current Opinion in Psychiatry, 20, 614–618. http://dx.doi.org/10.1097/YCO.0b013e3282f0ffd9. Schaumberg, K., Vinci, C., Raiker, J. S., Mota, N., Jackson, M., Whalen, D., et al. (2015). PTSDrelated alcohol expectancies and impulsivity interact to predict alcohol use severity in a substance dependent sample with PTSD41. (pp. 41–45), 41–45. http://dx.doi.org/10. 1016/j.addbeh.2014.09.022. Torchalla, I., Nosen, L., Rostam, H., & Allen, P. (2012). Integrated treatment programs for individuals with concurrent substance use disorders and trauma experiences: A systematic review and meta-analysis. Journal of Substance Abuse Treatment, 42(1), 65–77. http://dx.doi.org/10.1016/j.jsat.2011.09.001. Triffleman, E. (2000). Gender differences in a controlled pilot study of psychosocial treatments in substance dependent patients with post-traumatic stress disorder: Design considerations and outcomes. Alcoholism Treatment Quarterly, 18(3), 113–126. http://dx.doi.org/10.1300/J020v18n03_10. van Dam, D., Vedel, E., Ehring, T., & Emmelkamp, P. M. G. (2012). Psychological treatments for concurrent posttraumatic stress disorder and substance use disorder: A systematic review. Clinical Psychology Review, 32, 202–214. http://dx.doi.org/10.1016/j.cpr. 2012.01.004. Watkins, K. E., Hunter, S. B., Burnam, M. A., Pincus, H. A., & Nicholson, G. (2005). Review of treatment recommendations for persons with a co-occurring affective or anxiety and substance use disorder. Psychiatric Services, 56(8), 913–926. http://dx.doi.org/10. 1176/appi.ps.56.8.913. Weiss, N. H., Tull, M. T., Anestis, M. D., & Gratz, K. L. (2013). The relative and unique contributions of emotion dysregulation and impulsivity to posttraumatic stress disorder among substance dependent inpatients. Drug and Alcohol Dependence, 128, 45–51. http://dx.doi.org/10.1016/j.drugalcdep.2012.07.017. Weiss, N. H., Tull, M. T., Viana, A. G., Anestis, M. D., & Gratz, K. L. (2012). Impulsive behaviors as an emotion regulation strategy: Examining associations between PTSD, emotion dysregulation, and impulsive behaviors among substance dependent inpatients. Journal of Anxiety Disorders, 26, 453–458. http://dx.doi.org/10.1016/j. janxdis.2012.01.007. Wolf, E. J., Miller, M. W., Krueger, R. F., Lyons, M. J., Tsuang, M. T., & Koenen, K. C. (2010). Posttraumatic stress disorder and the genetic structure of comorbidity. Journal of Abnormal Psychology, 119, 320–330. http://dx.doi.org/10.1037/a0019035. Zayfert, C., & Becker, C. B. (2007). Cognitive-behavioral therapy for PTSD: A case formulation approach. New York: Guilford Press. Zlotnick, C., Johnson, J., & Najavits, L. M. (2009). Randomized controlled pilot study of cognitive-behavioral therapy in a sample of incarcerated women with substance use disorder and PTSD. Behavior Therapy, 40(4), 325–336. http://dx.doi.org/10. 1016/j.beth.2008.09.004.

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Ketamine for posttraumatic stress disorder.

Treatment of comorbid bipolar disorder and obsessive-compulsive disorder: a systematic review.

Posttraumatic Stress Disorder, Health Problems, and Depression Among African American Women in Residential Substance Use Treatment.

Psychometric Properties of the Modified Posttraumatic Stress Disorder Symptom Scale among Women with Posttraumatic Stress Disorder and Substance Use Disorders Receiving Outpatient Group Treatments.

Posttraumatic stress disorder.

Psychopharmacological treatment for military posttraumatic stress disorder: an integrative review.

A review of gambling disorder and substance use disorders.

Comorbid post-traumatic stress disorder in alcohol use disorder: relationships to demography, drinking and neuroimmune profile.

Towards a unitary perspective between post-traumatic stress disorder and substance use disorder. Heroin use disorder as case study.

Posttraumatic Stress Disorder: The Misappropriation of Military Suicide Causation and Medication Treatment of Posttraumatic Stress Disorder.

Multimodal approach to identifying malingered posttraumatic stress disorder: a review.

Psychological interventions for obsessive-compulsive personality disorder.