Integrated exposure-based therapy for co-occurring posttraumatic stress disorder and substance dependence: A randomized controlled trial. JAMA, the Journal of the American Medical Association, 308(7), 690-699

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia 2052.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 08/2012; 308(7):690-9. DOI: 10.1001/jama.2012.9071
Source: PubMed


There is concern that exposure therapy, an evidence-based cognitive-behavioral treatment for posttraumatic stress disorder (PTSD), may be inappropriate because of risk of relapse for patients with co-occurring substance dependence.
To determine whether an integrated treatment for PTSD and substance dependence, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), can achieve greater reductions in PTSD and substance dependence symptom severity compared with usual treatment for substance dependence.
Randomized controlled trial enrolling 103 participants who met DSM-IV-TR criteria for both PTSD and substance dependence. Participants were recruited from 2007-2009 in Sydney, Australia; outcomes were assessed at 9 months postbaseline, with interim measures collected at 6 weeks and 3 months postbaseline.
Participants were randomized to receive COPE plus usual treatment (n = 55) or usual treatment alone (control) (n = 48). COPE consists of 13 individual 90-minute sessions (ie, 19.5 hours) with a clinical psychologist.
Change in PTSD symptom severity as measured by the Clinician-Administered PTSD Scale (CAPS; scale range, 0-240) and change in severity of substance dependence as measured by the number of dependence criteria met according to the Composite International Diagnostic Interview version 3.0 (CIDI; range, 0-7), from baseline to 9-month follow-up. A change of 15 points on the CAPS scale and 1 dependence criterion on the CIDI were considered clinically significant.
From baseline to 9-month follow-up, significant reductions in PTSD symptom severity were found for both the treatment group (mean difference, -38.24 [95% CI, -47.93 to -28.54]) and the control group (mean difference, -22.14 [95% CI, -30.33 to -13.95]); however, the treatment group demonstrated a significantly greater reduction in PTSD symptom severity (mean difference, -16.09 [95% CI, -29.00 to -3.19]). No significant between-group difference was found in relation to improvement in severity of substance dependence (0.43 vs 0.52; incidence rate ratio, 0.85 [95% CI, 0.60 to 1.21), nor were there any significant between-group differences in relation to changes in substance use, depression, or anxiety.
Among patients with PTSD and substance dependence, the combined use of COPE plus usual treatment, compared with usual treatment alone, resulted in improvement in PTSD symptom severity without an increase in severity of substance dependence. Identifier: ISRCTN12908171.


Available from: Sudie E Back, May 27, 2014
    • "Screening for each of these problems concurrently in medical and primary care settings is essential to identify and address treatment needs. Research from substance use disorder literature clearly indicates that when PTSD symptoms remain untreated, effective intervention for either problem remains elusive (Back et al., 2006a, 2006b, 2014; Mills et al., 2012). Medical settings already screening for smoking behaviours may also include trauma exposure and alcohol use screenings to more effectively target referrals for patients. "
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    ABSTRACT: Background: Posttraumatic stress disorder (PTSD) and alcohol use disorders (AUDs) often co-occur with smoking and tobacco use disorders. Each of these disorders is known to have negative health consequences and impairment independently, but little is known about the impact of their co-occurrence. The aim of the present study is to examine the prevalence, correlates, order of onset, and impact of co-occurring daily smoking, PTSD, and AUDs. Method: The 2007 Australian National Survey of Mental Health and Wellbeing (2007 NSMHWB) was a nationally representative survey of 8841 Australians. The survey assessed for 12-month DSM-IV mental disorders; the age respondents first started smoking daily, experienced a traumatic event, or developed problems with alcohol; and self-reported mental and physical health and impairment. Results: There were systematic patterns of co-occurrence between daily smoking, PTSD, and AUDs. Daily smoking and problems with alcohol use tended to develop after first trauma exposure, which is broadly consistent with the self-medication hypothesis. Daily smoking, PTSD, and AUDs were also associated with additive negative effects on mental and physical health and functioning, after controlling for demographics. Conclusions: Smoking, PTSD, and AUDs commonly co-occur in this nationally representative sample of Australian men and women, and this comorbidity was associated with greater severity of mental and physical health problems and impairment in several areas of functioning. This study highlights the importance of identifying and eliminating these patterns of co-occurrence, potentially through integrated interventions.
    Drug and alcohol dependence 09/2015; 156. DOI:10.1016/j.drugalcdep.2015.09.007 · 3.42 Impact Factor
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    • "The significant reductions of PTSD symptom severity and drinking experienced across both treatment conditions at end-of-treatment and sustained over 6-and 12-month follow-up provide further support to extant research on the benefit of SS (see, e.g., van Dam et al. for a review of this literature) in amelioration of SUD outcomes. Since PTSD improvements have been shown to lead to later substance use improvements (Hien et al., 2010; Mills et al., 2012; Morgan-Lopez et al., 2014 "
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    ABSTRACT: Objective: The current study marks the first randomized controlled trial to test the benefit of combining Seeking Safety (SS), a present-focused cognitive-behavioral therapy for co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), with sertraline, a front-line medication for PTSD shown to also impact drinking outcomes. Method: Sixty-nine participants (81% female; 59% African American) with primarily childhood sexual (46%) and physical (39%) trauma exposure, and drug dependence in addition to AUD were randomized to receive a partial-dose (12 sessions) of SS with either sertraline (n = 32; M = 7 sessions) or placebo (n = 37; M = 6 sessions). Assessments conducted at baseline, end-of-treatment, 6- and 12-months posttreatment measured PTSD and AUD symptom severity. Results: Both groups demonstrated significant improvement in PTSD symptoms. The SS plus sertraline group exhibited a significantly greater reduction in PTSD symptoms than the SS plus placebo group at end-of-treatment (M difference = -16.15, p = .04, d = 0.83), which was sustained at 6- and 12-month follow-up (M difference = -13.81, p = .04, d = 0.71, and M difference = -12.72, p = .05, d = 0.65, respectively). Both SS groups improved significantly on AUD severity at all posttreatment time points with no significant differences between SS plus sertraline and SS plus placebo. Conclusion: Results support the combining of a cognitive-behavioral therapy and sertraline for PTSD/AUD. Clinically significant reductions in both PTSD and AUD severity were achieved and sustained through 12-months follow-up, Moreover, greater mean improvement in PTSD symptoms was observed across all follow-up assessments in the SS plus sertraline group. (PsycINFO Database Record
    Journal of Consulting and Clinical Psychology 04/2015; 83(2):359-369. DOI:10.1037/a0038719 · 4.85 Impact Factor
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    • "The mechanisms underlying this comorbidity remain unclear, but both conditions are associated with high levels of stress reactivity. Recently, a behavioral intervention has demonstrated efficacy in reduction of PTSD symptoms in this population (Mills et al. 2012), without similar improvement substance dependence Laura E. Kwako and David T. George contributed equally to this work. "
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    ABSTRACT: Rationale Posttraumatic stress disorder (PTSD) and alcoholism are frequently comorbid, suggesting the possibility of overlapping neural substrates. The neurokinin 1 (NK1) receptor for substance P (SP) has been implicated in both stress- and alcohol-related behaviors. The NK1 antagonist aprepitant, clinically available as a treatment for chemotherapy-induced nausea, offers a tool to probe a potential role of the SP/NK1 system in comorbid PTSD and alcoholism. Objectives The aim of this study is to evaluate the efficacy of aprepitant for treatment of comorbid PTSD and alcoholism. Methods Fifty-three patients with PTSD and alcoholism were admitted for 4 weeks to an inpatient unit at the NIH Clinical Center and randomized to double-blind aprepitant (125 mg/day; based on PET studies reporting >90 % central receptor occupancy at this dose) or placebo. After reaching steady state, subjects were assessed for PTSD symptom severity, behavioral and neuroendocrine responses to stress and alcohol cues, and functional magnetic resonance imaging (fMRI) responses to stimuli with positive or negative emotional valence. Results Aprepitant treatment had no effect on PTSD symptoms or subjective or physiological responses to stress or alcohol cues. However, aprepitant robustly potentiated ventromedial prefrontal cortex (mPFC) fMRI responses to aversive visual stimuli. Conclusions Despite the lack of effect on PTSD symptoms and responses to stress/alcohol cues, NK1 antagonism activated the ventral mPFC, an area considered hypoactive in PTSD, during exposure to aversive stimuli. Because this brain area is critically important for extinction of fear memories and in alcohol craving and relapse, our finding suggests that NK1 antagonism might be a useful pharmacological treatment to enhance extinction-based cue-exposure therapies.
    Psychopharmacology 07/2014; 232(1). DOI:10.1007/s00213-014-3665-4 · 3.88 Impact Factor
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