Exposure-based Therapy Research Articles

Effects of a cognitive-behavioral exposure-based body image therapy for overweight females with binge eating disorder: a pilot study

BackgroundAlthough not part of the diagnostic criteria of the DSM-5, body image disturbance seems to be a relevant feature of Binge Eating Disorder (BED) as well as of other eating disorders such as Anorexia Nervosa (AN) or Bulimia Nervosa (BN). Hence, the aim of the present pilot study was to assess the changeability of body image disturbance in a sample of overweight females with BED by a cognitive-behavioral treatment, directly addressing body image disturbance.MethodOverweight females (N = 34) with BED were randomized to a manualized body image therapy or a waiting-list control group. The final sample consisted of n = 15 participants in the intervention group and n = 19 in the control group due to two drop-outs in the control condition. Before and after the intervention or the waiting period, respectively, participants filled out a questionnaire battery assessing several body image and eating disorder related features. To quantify the perceptual component of body image disturbance, a digital photo distortion technique based on a picture of each participant taken in a standardized suit was applied.ResultsIn a two-way ANOVA, significant Time × Group interactions were found for eating and shape concerns, drive for thinness, body dissatisfaction, depressiveness and low self-esteem. Follow-up t-tests indicated a significant symptom reduction of a generally high magnitude in the intervention group. No significant changes concerning body checking and the estimations of one’s own “real”, “felt” and “ideal” body dimensions were found.ConclusionThe strong symptom reduction in the cognitive-affective component of body image disturbance indicates that an exposure-based cognitive-behavioral body image intervention is a promising treatment module for overweight females with BED, but future research with a larger sample size is needed to quantify possible changes in all components of body image.

Efficacy of group psychotherapy for posttraumatic stress disorder: Systematic review and meta-analysis of randomized controlled trials

Objective: The present meta-analysis evaluates the efficacy of group psychotherapy for post-traumatic stress disorder (PTSD) in adults directly compared to no treatment or active treatments examined in randomized controlled trials (RCTs). Method: Electronic databases were searched for eligible studies. Effects on PTSD symptoms, depression, and anxiety were extracted. Between- and within-group effect sizes (Hedges’ g) were calculated using a random-effects model. Data were adjusted to account for dependencies among observations in groups. Results: Twenty RCTs were included comprising 2244 individuals. Results showed significant effects of group psychotherapy in reducing symptoms of PTSD compared to no-treatment control groups (k = 13; g = 0.70; 95% CI: 0.41; 0.99). No significant differences in efficacy were found between group psychotherapy and other active treatments (k = 8; g = 0.13; 95% CI: −0.16; 0.42). Moderator analyses confirmed gender and trauma type as important moderators of within-treatment effects for PTSD. Conclusions: Group treatments are associated with improvements in symptoms of PTSD. Particularly, the efficacy of exposure-based cognitive-behavioral group therapy (group CBT) is empirically well demonstrated. Still little is known about the effects of group treatment approaches other than CBT and the comparative efficacy to alternative treatments such as individual therapy or pharmacotherapy.Clinical or Methodological Significance of this Article: This review provides an empirical base for group therapy as a viable treatment alternative for future PTSD practice guidelines. Although less is known about its comparative efficacy to alternative PTSD treatments such as individual therapy or pharmacotherapy, sufficient evidence exists to recommend group therapy (particularly exposure-based group CBT) for those who might not be able to access alternative treatments. Trauma type and gender proved to be important moderators of group treatment outcome. The results further indicate that the evidence base of recommendations for group therapy in current international treatment guidelines needs to be updated.

New pharmacological strategies for augmenting extinction learning in anxiety disorders

Abstract Despite advances in the treatment of fear-, anxiety- and trauma-related disorders, a considerable proportion of patients shows only partial long-term therapeutic benefit with existing treatments. A promising option in improving therapy is speeding up and boosting the effect of exposure-based therapy (EBT) by pharmacological interventions. Here, we will discuss select examples of novel concepts in augmenting fear extinction, the central mechanisms of EBT. Based on accumulating knowledge from animal and human studies concerning the neurocircuitries and neurobiological mechanisms underlying successful fear extinction, diverse potential pharmacological targets have been identified to optimize the efficacy of fear extinction. We focus here on selected examples of these targets and present translational evidence for strengthening fear inhibitory learning by using L-DOPA and D-cycloserine. Furthermore, the potential of HDAC inhibitors and microRNAs (e. g. miR-144) as epigenetic targets, as well as neuropeptide S as a model substance with combined acute anxiolytic and extinction-facilitating properties are discussed. The presented mechanisms represent promising novel strategies that may be useful in the future for augmenting the efficacy and improving the acceptance of EBT in the treatment of anxiety disorders, although further work remains to be done in characterising the underlying modes of action and safety aspects.

A randomized-controlled trial of cognitive–behavioral therapy for depression with integrated techniques from emotion-focused and exposure therapies

ABSTRACTBackground: Emotional processing (EP) is hypothesized to be a key mechanism of change in psychotherapy that may enhance its long-term efficacy. To study the effects of fostering EP in psychotherapy for depression, this randomized-controlled clinical trial compares the efficacy and pattern of change of a cognitive–behavioral therapy that integrates emotion-focused techniques within an exposure framework (Exposure-Based Cognitive Therapy for depression; EBCT-R) to a standard cognitive–behavioral therapy (CBT). Methods: One hundred and forty-nine depressed outpatients were randomized to a maximum of 22 sessions of manualized EBCT-R (N = 77) or CBT (N = 72). Primary outcomes were self-reported and clinician-rated depressive symptoms at posttreatment and 12-month follow-up. Secondary outcomes were self-esteem, interpersonal problems, and avoidance thoughts and behaviors. Results: Depressive symptoms improved significantly over therapy in both treatments, with large within-group effect sizes for CBT (d = −1.95) and EBCT-R (d = −1.77). The pattern of depression change during treatment did not differ between treatments. Symptom relief lasted over 12 months and did not differ between EBCT-R and CBT. Conclusions: Results suggest that both treatments produced significant short- and long-term improvement in depression symptoms, but the integration of emotion-focused techniques within an exposure framework did not have added benefit.Trial registration: ClinicalTrials.gov Identifier: NCT01012856Clinical or methodological significance of this article: This trial compares cognitive–behavioral therapy (CBT) with a similarly structured CBT that was designed to foster emotional processing by integrating emotion-focused techniques within an exposure framework. Results indicate that this form of assimilative integration did not improve outcomes at 12-month follow-up.

Practitioner Review: Definition, recognition, and treatment challenges of irritability in young people.

Irritability is one of the most common reasons for referral to child and adolescent mental health services and is the main characteristic of the new diagnosis of disruptive mood dysregulation disorder (DMDD). However, the recognition and management of irritability presents a major challenge in clinical practice and may be partly responsible for the dramatic increase in antipsychotic prescribing in recent years. In this review, we provide up-to-date information on the definition and mechanisms underlying irritability, and its assessment in clinical practice. We aim to discuss the latest research on DMDD, and the presence of severe irritability in the context of other disorders, as well as to recommend a treatment algorithm. Severe irritability is associated with aberrant reward processing and bias toward threatening stimuli. Several measures are available to easily assess irritability. The recent diagnosis of DMDD captures children whose main problem is severe irritability and differ from those with bipolar disorder in longitudinal outcomes, family history, and behavioral and neural correlates. Treatment of irritability might depend on the context it appears. Indirect evidence suggests that parent management training (PMT) and cognitive behavioral therapy (CBT) are the most supported psychological treatments for irritability. Irritability, recognized as a mood problem rather than a purely behavioral manifestation, is a common condition for young people. Practitioners should not ignore irritability as it is associated with substantial morbidity and impairment. Although there are no trials with irritability as main outcome, clinicians can apply several existing pharmacological and psychological interventions for its treatment. Also, new promising approaches relying on pathophysiological findings, such as exposure-based cognitive behavioral therapy techniques and interpretation bias training (IBT), are being currently investigated.

The impact of exposure-based cognitive behavior therapy for severe health anxiety on self-rated health: Results from a randomized trial

ObjectiveSelf-rated health (SRH) has been shown to be a stable predictor of illness and mortality. Improvement in SRH, even in the absence of change in objective health, predicts better health and reduced mortality. Severe health anxiety (SHA) is characterized by fear of illness and distorted health perception. The objective of the present study was to investigate if exposure-based cognitive behavior therapy (CBT) for SHA can lead to improvement in SRH and whether this improvement is mediated by reduced health anxiety. MethodsData were collected from a randomized controlled trial where participants with SHA were allocated to 12weeks of exposure-based CBT (n=99) for SHA or to a no treatment control condition (n=33). The mediation analysis was based on SRH- and health anxiety data collected weekly during the treatment phase. ResultsLinear mixed effects models analysis showed a significant interaction effect of group and time indicating superior improvements in SRH in exposure-based CBT compared to the control condition (Z=2.69, p=0.007). The controlled effect size was moderately large (d=0.64) and improvements were stable at 1-year follow-up. Reduced health anxiety was a significant mediator of improvement in SRH. Conclusions12weeks of exposure-based CBT for SHA can lead to significant improvements in SRH. Considering the previously established importance of SRH as a predictor for disease and mortality, exposure-based CBT for severe health anxiety may lead to improvements on several important health parameters, possibly even increasing the likelihood of longevity.

Increasing Availability of Exposure Therapy Through Intensive Group Treatment for Childhood Anxiety and OCD.

Archival data were used to examine the feasibility of a 5-day, clinic-based, intensive exposure-based cognitive-behavioral group therapy for childhood anxiety disorders (CADs) and obsessive-compulsive disorder (OCD). Participants were 143 children (82 girls) aged 6 to 19 years ( M = 13.93 years, SD = 2.9 years) with CADs or OCD (or both) in 28 consecutive groups. Repeated-measures ANOVA in the subsample ( n = 57) with complete treatment data indicated positive change on all variables from pretreatment to posttreatment with few differences between CADs and OCD patients. Effect sizes were moderate to large for anxiety symptoms (parent reported = 0.74, child reported = 0.65) and impairment (parent reported = 1.02, child reported = 0.69). The intensive group protocol required fewer sessions and 36% fewer therapist-hours per patient than the individually administered protocol. The program increased treatment availability for families from diverse geographic areas ( M distance traveled to clinic = 407 miles, SD = 786.4 miles). These findings support further, well-controlled examination of the 5-day intensive group treatment protocol's efficacy and potential to increase availability of evidence-based exposure therapy.

Safety Behavior After Extinction Triggers a Return of Threat Expectancy

Safety behavior is involved in the maintenance of anxiety disorders, presumably because it prevents the violation of negative expectancies. Recent research showed that safety behavior is resistant to fear extinction. This fear conditioning study investigated whether safety behavior after fear extinction triggers a return of fear in healthy participants. Participants learned that two stimuli (A and C) were followed by an aversive loud noise (“threat”), and one stimulus (B) was not. Participants then learned to use safety behavior that prevented the loud noise. Next, A and C were no longer followed by the loud noise, which typically led to extinction of threat expectancy. Safety behavior then became available again for C, but not for A and B. All participants used safety behavior on these C trials. In a final test phase, A, B, and C were presented once without the availability to use safety behavior. At each stimulus presentation, participants rated threat expectancy by indicating to what extent they expected that the loud noise would follow. Compared with the last extinction trial, threat expectancy increased for C in the test phase, whereas it did not increase for A and B. Hence, safety behavior after the extinction of classically conditioned fear caused a partial return of fear. The findings suggest that safety behavior may be involved in relapse after exposure-based therapy for anxiety disorders.

Genome-wide expression and response to exposure-based psychological therapy for anxiety disorders

Exposure-based psychological treatments for anxiety have high efficacy. However, a substantial proportion of patients do not respond to therapy. Research examining the potential biological underpinnings of therapy response is still in its infancy, and most studies have focussed on candidate genes. To our knowledge, this study represents the first investigation of genome-wide expression profiles with respect to treatment outcome. Participants (n=102) with panic disorder or specific phobia received exposure-based cognitive behavioural therapy. Treatment outcome was defined as percentage reduction from baseline in clinician-rated severity of their primary anxiety diagnosis at post treatment and 6 month follow-up. Gene expression was determined from whole blood samples at three time points using the Illumina HT-12v4 BeadChip microarray. Linear regression models tested the association between treatment outcome and changes in gene expression from pre-treatment to post treatment, and pre-treatment to follow-up. Network analysis was conducted using weighted gene co-expression network analysis, and change in the detected modules from pre-treatment to post treatment and follow-up was tested for association with treatment outcome. No changes in gene expression were significantly associated with treatment outcomes when correcting for multiple testing (q<0.05), although a small number of genes showed a suggestive association with treatment outcome (q<0.5, n=20). Network analysis showed no association between treatment outcome and change in gene expression for any module. We report suggestive evidence for the role of a small number of genes in treatment outcome. Although preliminary, these findings contribute to a growing body of research suggesting that response to psychological therapies may be associated with changes at a biological level.

Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA).

3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA's effect on extinction. We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

Exposure-Based Therapy for Symptom Preoccupation in Atrial Fibrillation: An Uncontrolled Pilot Study

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Patients often experience a range of symptoms resulting in a markedly reduced quality of life, and commonly show symptom preoccupation in terms of avoidance and control behaviors. Cognitive behavior therapy (CBT) has been shown to improve symptom burden and quality of life in other somatic disorders, but has never been evaluated in patients with AF. The purpose of this study was to evaluate the potential efficacy and feasibility of an AF-specific CBT protocol in an uncontrolled pilot study. The study included 19 patients with symptomatic paroxysmal (intermittent) atrial fibrillation who were assessed pre- and posttreatment and at 6-month follow-up. The CBT lasted 10 weeks and included exposure to physical sensations similar to AF symptoms, exposure to avoided situations or activities, and behavioral activation. We observed large within-group improvements on the primary outcome AF-specific quality of life measurement AFEQT posttreatment (Cohen’s d = 1.54; p < . 001) and at 6-month follow-up (d = 1.15; p < . 001). We also observed improvements in self-reported frequency and severity of AF symptoms. All participants completed the treatment and treatment satisfaction was high. This study demonstrates the potential efficacy and feasibility of a novel CBT approach to reduce symptoms and increase quality of life in AF patients.

Sudden gains in exposure-focused cognitive-behavioral group therapy for panic disorder.

Sudden gains are common in panic disorder patients undergoing exposure-based cognitive-behavioral group therapy. Sudden gains during exposure-focused therapy are linked to greater improvement in panic disorder severity and functional impairment. The positive impact of sudden gains on panic disorder severity and functional impairment is maintained in the long term.

The mediating effect of mindful non-reactivity in exposure-based cognitive behavior therapy for severe health anxiety

Exposure-based cognitive behavior therapy (CBT) has been shown to be effective in the treatment of severe health anxiety, but little is known about mediators of treatment effect. The aim of the present study was to investigate mindful non-reactivity as a putative mediator of health anxiety outcome using data from a large scale randomized controlled trial. We assessed mindful non-reactivity using the Five Facets Mindfulness Questionnaire-Non-Reactivity scale (FFMQ-NR) and health anxiety with the Short Health Anxiety Inventory (SHAI). Participants with severe health anxiety (N=158) were randomized to internet-delivered exposure-based CBT or behavioral stress management (BSM) and throughout the treatment, both the mediator and outcome were measured weekly. As previously reported, exposure-based CBT was more effective than BSM in reducing health anxiety. In the present study, latent process growth modeling showed that treatment condition had a significant effect on the FFMQ-NR growth trajectory (α-path), estimate=0.18, 95% CI [0.04, 0.32], p=.015, indicating a larger increase in mindful non-reactivity among participants receiving exposure-based CBT compared to the BSM group. The FFMQ-NR growth trajectory was significantly correlated with the SHAI trajectory (β-path estimate=−1.82, 95% CI [−2.15, −1.48], p<.001. Test of the indirect effect, i.e. the estimated mediation effect (αβ) revealed a significant cross product of −0.32, which was statistically significant different from zero based on the asymmetric confidence interval method, 95% CI [−0.59, −0.06]. We conclude that increasing mindful non-reactivity may be of importance for achieving successful treatment outcomes in exposure-based CBT for severe health anxiety.

Journal Digest

Journal Digest

Pharmacological modulation of metabotropic glutamate receptor subtype 5 and 7 impairs extinction of social fear in a time-point-dependent manner

Pharmacological modulation of metabotropic glutamate receptor subtype 5 (mGluR5) and 7 (mGluR7) was shown to attenuate the acquisition and to facilitate the extinction of cued and contextual, non-social, fear. Using the allosteric mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and the allosteric mGluR7 agonist N,N’-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), we aimed to study how pharmacological blockade of mGluR5 and activation of mGluR7 influence acquisition and extinction of social fear in mice. We could show that when administered before social fear conditioning, neither MPEP nor AMN082 affected acquisition and extinction of social fear, suggesting that mGluR5 inactivation and mGluR7 activation do not alter social fear. However, when administered before social fear extinction, both MPEP and AMN082 impaired social fear extinction and extinction recall. These findings suggest that mGluR5 inactivation and mGluR7 activation are unlikely to prevent the formation of traumatic social memories. Furthermore, medication strategies aimed at augmenting exposure-based therapies for psychiatric disorders associated with social deficits via modulation of mGluR5 and mGluR7 must be pursued cautiously because of their potential to delay social fear extinction processes.

Assessment and Treatment of Anxiety Among Children and Adolescents.

Among children and adolescents, anxiety disorders are common psychiatric disorders that confer risk of comorbid psychiatric disorders and social and academic impairment. This review focuses on the assessment and treatment of anxiety disorders among children and adolescents, with attention to separation anxiety disorder, social phobia disorder (social anxiety disorder), panic disorder, and generalized anxiety disorder. Comprehensive assessment of child and adolescent anxiety disorders benefits from a multimethod approach to evaluation and diagnosis, including semistructured interviews; child and informant questionnaires; collateral information from parents, teachers, pediatricians, and school psychologists; and behavioral observations. Because anxiety symptoms can include avoidance behaviors, somatic complaints, social difficulties, and sleep disturbances, consideration of a differential diagnosis is important. Among the available psychosocial interventions, cognitive-behavioral therapy (CBT) and exposure-based therapies have emerged as the most well-established treatment approaches for addressing anxiety disorders among children and adolescents. Pharmacologically, selective serotonin reuptake inhibitors (SSRIs) have been established to be safe and efficacious for the treatment of pediatric anxiety and are considered the medications of choice for this population. Research indicates that CBT plus SSRI medication is the most effective treatment of anxiety for youths ages seven to 17, compared with either CBT or medication alone. Medication monotherapy and CBT monotherapy have also been demonstrated to be effective treatments.

Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

The ability to assign safety to stimuli in the environment is integral to everyday functioning. A key brain region for this evaluation is the ventromedial prefrontal cortex (vmPFC). To investigate the importance of vmPFC safety signaling, we used neuroimaging of Pavlovian fear reversal, a paradigm that involves flexible updating when the contingencies for a threatening (CS+) and safe (CS-) stimulus reverse, in a prototypical disorder of inflexible behavior influenced by anxiety, Obsessive Compulsive Disorder (OCD). Skin conductance responses in OCD patients (n = 43) failed to differentiate during reversal compared with healthy controls (n = 35), although significant differentiation did occur during early conditioning and amygdala BOLD signaling was unaffected in these patients. Increased vmPFC activation (for CS+ > CS-) during early conditioning predicted the degree of generalization in OCD patients during reversal, whereas vmPFC safety signals were absent throughout learning in these patients. Regions of the salience network (dorsal anterior cingulate, insula, and thalamus) showed early learning task-related hyperconnectivity with the vmPFC in OCD, consistent with biased processing of the CS+. Our findings reveal an absence of vmPFC safety signaling in OCD, undermining flexible threat updating and explicit contingency knowledge. Although differential threat learning can occur to some extent in the absence of vmPFC safety signals, effective CS- signaling becomes crucial during conflicting threat and safety cues. These results promote further investigation of vmPFC safety signaling in other anxiety disorders, with potential implications for the development of exposure-based therapies, in which safety signaling is likely to play a key role.

D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders

Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.

Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE): A Pilot Study in Alcohol-dependent Women.

Posttraumatic stress disorder (PTSD) and substance use disorders are highly comorbid. Effective treatments are largely lacking. This pilot study evaluated the safety and feasibility of a novel intervention, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), in preparation for a randomized controlled trial. Twenty-two treatment-seeking women with current DSM-IV-TR PTSD and alcohol dependence (AD) were recruited. Participants received COPE. Safety and feasibility were evaluated, as were efficacy-related outcomes: PTSD and depression symptom severity, alcohol use, craving, and dependence severity. No adverse events occurred. COPE was implemented in routine clinical practice. Among the assessed women, 95.8% were eligible to participate. Treatment attendance and completion were higher than in previous studies. Post treatment, all efficacy-related outcomes, including PTSD and depression symptom severity, alcohol use, craving, and dependence severity, were significantly reduced. COPE was safe and feasible to use. Concerns that trauma-focused, exposure-based therapy might promote relapse in this population appear unwarranted. Our findings provide initial evidence suggestive of COPE efficacy for comorbid PTSD and AD in women. These results provide a strong rationale for investigating the efficacy of COPE for comorbid PTSD and AD in women in a randomized controlled trial.