Are 60-minute prolonged exposure sessions with 20-minute imaginal exposure to traumatic memories sufficient to successfully treat PTSD? A randomized noninferiority clinical trial.

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Are 60-Minute Prolonged Exposure Sessions With 20-Minute Imaginal Exposure to Traumatic Memories Sufficient to Successfully Treat PTSD? A Randomized Noninferiority Clinical Trial Nitsa Nacasch Tel-Aviv Brull Community Mental Health Center Jonathan D. Huppert The Hebrew University of Jerusalem Yi-Jen Su National Taiwan University Yogev Kivity The Hebrew University of Jerusalem Yula Dinshtein Tel-Aviv Brull Community Mental Health Center Rebecca Yeh Edna B. Foa University of Pennsylvania

The study aims to determine whether 60-minute sessions of prolonged exposure (PE) that include 20 minutes of imaginal exposure (IE) are noninferior to the standard We want to thank Professor Joseph Zohar for his contribution to the design and implementation of the study, to Dr. Miki Polliack, Yonina Zilbermintz, Rachel Gold, and Miri Shalit for their help in the implementation of the study and to the therapists for their rigorous implementation of the treatment procedures. Our thanks are extended to the research assistants at Chaim Sheba Medical Center, Dana Tzur and Dr. Lea Fostick, and to the research assistants for their day-to-day help in the study-related activities. Last but not least we want to express our gratitude to Josephine Curry, Joseph Carpenter, and Rebecca Yeh from the Department of Psychiatry at the University of Pennsylvania for their diligent work in preparing the manuscript for submission. Address correspondence to Edna B. Foa, Ph.D., Department of Psychiatry, University of Pennsylvania, 3535 Market Street, 6th Floor, Philadelphia, PA 19104; e-mail: [email protected]. 0005-7894/© 2014 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.

90-minute sessions that include 40 minutes of IE in treating posttraumatic stress disorder (PTSD) and to explore the relationship of treatment outcome to within- and betweensession habituation and change in negative cognitions. Thirty-nine adult veterans with chronic PTSD were randomly assigned to 90-minute (n = 19) or 60-minute (n = 20) sessions of PE. PTSD symptoms were assessed by an unaware independent evaluator before and after treatment and at 6-month follow-up. Self-reports of depression and negative cognitions were assessed before and after treatment. Participants in both conditions showed significant reductions in PTSD symptoms. Sixty-minute sessions were found to be noninferior to 90-minute sessions in reducing PTSD symptoms, as the upper bound of the 95% confidence interval for the difference between conditions in the PTSD Symptom Scale–Interview (posttreatment: 6.00; follow-up: 6.77) was below the predefined noninferiority margin (7.00). Participants receiving shorter sessions

Please cite this article as: Nitsa Nacasch, et al., Are 60-Minute Prolonged Exposure Sessions With 20-Minute Imaginal Exposure to Traumatic Memories Sufficient to Successfully Treat ..., Behavior Therapy (2015), http://dx.doi.org/10.1016/j.beth.2014.12.002

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showed less within- and between-session habituation than those receiving longer sessions, but no group differences in reductions in negative cognitions were found. The current findings indicate that the outcomes of 60-minute sessions of PE do not differ from those of 90-minute sessions. In addition, change in trauma-related cognitions and betweensession habituation are both potential mechanisms of PE.

Keywords: posttraumatic stress disorder; prolonged exposure; habituation; fear activation; emotional processing

PROLONGED EXPOSURE THERAPY (PE; Foa, Hembree, & Rothbaum, 2007), a specific exposure therapy program for posttraumatic stress disorder (PTSD), is a highly effective treatment for PTSD across a variety of traumas (Foa et al., 2005; Powers, Halpern, Ferenschak, Gillihan, & Foa, 2010). The PE program usually consists of 8 to 15 weekly or twice-weekly sessions, each lasting about 90 minutes, with 45 to 60 minutes of imaginal exposure. The three main components of PE are in vivo exposure, imaginal exposure, and processing of the imaginal exposure (McLean & Foa, 2011). The rationale of PE is based on emotional processing theory (EPT; Foa, Huppert, & Cahill, 2006; Foa & Kozak, 1986). Briefly, EPT proposes that PTSD reflects the presence of a pathological fear (emotional) structure in which normally safe stimuli representations are associated with the meaning of danger, and normal responses to trauma are associated with the meaning of selfincompetence. Thus, EPT posits that the erroneous cognitions that “the world is extremely dangerous” and “I am extremely weak and incompetent” mediate the development and maintenance of PTSD by promoting avoidance that prevents the individual from testing and disconfirming these cognitions. According to EPT, treatment that aims at ameliorating PTSD symptoms should correct these erroneous associations, either by introducing new information or strengthening nonpathological associations and memories (Foa et al., 2006, see also Brewin, 2006). The course by which these changes occur is called emotional processing. In PE, emotional processing is achieved through the use of in vivo exposure to avoided trauma-related situations and imaginal exposure to the traumatic event (revisiting of the traumatic memory in imagination and recounting it aloud) followed by postexposure processing, (i.e., discussion of the revisiting experience), which entails asking how their experience was while retelling the trauma, what they learned from the retelling or trauma, acknowledging the courage of the patient for having recounted the story, emphasizing to the patients that they did not fall apart from confronting the memory, and exploring how realistic

are their emotions such as guilt or shame in an indirect and empathic manner. Prior studies have demonstrated the efficacy of imaginal exposure alone (Bryant, Moulds, Guthrie, Dang, & Nixon, 2003; Tarrier et al., 1999) and in vivo exposure alone (Marks, Lovell, Noshirvani, Livanou, & Thrasher, 1998) in treating PTSD. Furthermore, one study (Bryant et al., 2008) that included in vivo and imaginal exposure but excluded processing after imaginal exposure showed inferior outcomes compared with studies that included both in vivo exposure and imaginal exposure followed by cognitive restructuring, suggesting the importance of conducting processing after imaginal exposure. EPT posits two mechanisms of PE: activation (emotional engagement) of the trauma memory through imaginal and in vivo exposure, and presentation of information during exposure that disconfirms the expected harm that leads to reductions in negative cognitions. In addition, EPT proposes three indicators of emotional processing: fear activation, within-session habituation (i.e., reduction in distress levels from the beginning to end of exposure to a feared memory or stimulus in a treatment session), and between-session habituation (i.e., reduction of peak distress levels across successive exposure sessions). These indicators, along with changes in negative cognitions, are hypothesized to be associated with successful outcome (cf. Zalta et al., 2013). Indeed, the rationale for extending imaginal exposure to 60 minutes was derived from the supposition that within-session habituation is associated with reduction in PTSD symptoms. However, although longer exposures have been shown to promote greater within-session habituation than shorter exposures (Chaplin & Levine, 1981; Rabavilas, Boulougouris, & Stefanis, 1976; van Minnen & Foa, 2006), between-session—but not within-session— habituation has been associated with treatment outcome (Jaycox, Foa, & Morral, 1998; van Minnen & Hagenaars, 2002). Moreover, in a nonrandomized study, van Minnen and Foa (2006) found that 60-minute imaginal exposures did not produce superior outcomes to 30-minute imaginal exposures despite greater within-session habituation in the longer exposures. Furthermore, although no differences were found in between-session habituation between the longer and shorter exposures, betweensession habituation was related to treatment outcome. This raises questions about the importance of within-session habituation as a reliable indicator of emotional processing proposed by EPT. In addition to their theoretical implications, van Minnen and Foa’s (2006) findings are of practical importance. At present, there has been widespread dissemination of PE from academic settings into


sixty vs. ninety minutes of prolonged exposure community practice (Foa et al., 2005; Karlin et al., 2010; McLean & Foa, 2011). One barrier for using PE in community clinics is the limitation often imposed on session length by reimbursement policies. Reducing the length of PE sessions from 90 minutes to the “standard” psychotherapy 60-minute sessions would eliminate this critical barrier. Indeed, the impetus to reduce the length of sessions in van Minnen and Foa’s study was the change in reimbursement regulations in the Netherlands. Moreover, the efficacy of PE in the treatment of individuals suffering from combat- and terror-related PTSD has been demonstrated in several recent studies (e.g., Nacasch et al., 2011; Schneier et al., 2012; Tuerk et al., 2011). The number of PTSD cases related to combat and terror is increasing due to the significant rise in worldwide combat and terror violence over the last decade. Shortened PE is of great value to address the urgent need for efficacious and time-limited treatment for this population. Despite the promising results of van Minnen and Foa (2006), their study contains a number of methodological limitations that prevent strong conclusions from their work. First, patients were not randomly assigned to the two conditions. Second, outcome variables were measured using self-report data. Third, the follow-up period was only 1 month, which is not long enough to assess whether participants in the 30-minute exposure condition would be more likely to relapse than those in the 60-minute exposure condition. Last, although the relationships of within- and betweensession habituation to outcome were examined in that study, a critical mechanism of PE, reduction in negative trauma-related cognitions, was not assessed. Thus, the effects of length of treatment on cognitions could not be examined. Given these limitations, the efficacy of shortened imaginal exposure still remains unestablished and, as the authors stated in their limitation, needs to be replicated using more rigorous methodology. The goals of the present study were to replicate the findings of van Minnen and Foa (2006) and to further examine the theoretical and practical implications of reducing the length of imaginal exposure in PE by comparing the efficacy of 90-minute PE sessions that included 40-minute imaginal exposures with 60-minute PE sessions that included 20-minute imaginal exposure in participants with chronic PTSD. To address the limitations of van Minnen and Foa’s study, in the present study (a) participants were randomly assigned to 90- or 60-minute PE sessions, (b) shorter length of imaginal exposure (i.e., 20 minutes) was adopted, (c) outcome was assessed by evaluators unaware of treatment condition, (d) follow-up assessment of PTSD symptom

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severity was extended to 6 months, and (e) a measure of trauma-related cognitions was included. The above design allowed us to examine the following hypotheses: (a) noninferiority: patients who received 60-minute sessions with 20-minute imaginal exposure would not have significantly less reduction in PTSD symptoms, depression, and trauma-related cognitions than patients who received 90-minute sessions with 40-minute imaginal exposure. Confirmation of noninferiority in this trial was established by showing that the difference in mean improvement of outcome measures is smaller than a prespecified noninferiority margin, as defined by the reliable change index developed by Jacobson and Truax (1991) and determined for PTSD studies by Devilly and Foa (2001); (b) habituation: patients receiving 40-minute imaginal exposure would exhibit greater within-session habituation than those receiving 20-minute imaginal exposure but would not differ in the degree of between-session habituation; (c) there would be a significant relationship of between-session habituation, but not within-session habituation, and reduction in PTSD symptom severity; and (d) there would be a significant relationship between change in trauma-related cognitions and change in PTSD symptoms in both conditions.

Method participants To be eligible for the study, patients had to meet a diagnosis of PTSD and to experience moderate to severe symptoms for at least 3 months (PTSD Symptoms Scale–Interview [PSS-I; Foa, Riggs, Dancu, & Rothbaum, 1993] score ≥ 20), comparable to previous randomized clinical trial (RCT) studies for standard PE (e.g., Foa, Dancu, et al., 1999; Foa et al., 2005). PTSD had to be at least as severe as other psychiatric diagnoses. If treated with medications, patients had to be on a stable regimen for at least 3 months prior to pretreatment evaluation and remain on that dosage throughout treatment. Adherence was monitored by the patient’s report to the psychiatrist. Exclusion criteria were current active substance dependence, current psychotic symptoms, bipolar disorder, or severe dissociative symptoms. Patients deemed at high risk for suicidal behavior (i.e., with intent or plan or both) were also excluded. Severe dissociative symptoms were determined at intake through administration of the Dissociative Experiences Scale (van IJzendoorn & Schuengel, 1996) and an unstructured clinical interview by the first author, a psychiatrist (e.g., a patient became agitated and stopped answering questions for a number of minutes, appearing to be dissociated, multiple times throughout the intake interview).


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Fifteen (75%) of the 60-minute group and 14 (74%) of the 90-minute group were on medications (predominantly selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs]) during the entire study. The first authors monitored the medication of all patients in the study. None of the patients changed their medication regimen during their participation in the study. Between March 2005 and March 2010, 84 veterans were referred to the PE clinic of the outpatient psychiatric trauma unit at Sheba Medical Center for participation in the current study. They were referred either by psychiatrists of the trauma unit or by therapists from other mental health clinics. After an initial screening assessment, eligible individuals completed all assessments described below. Of these individuals, 39 participated in the study. Nineteen of them were randomized to 90-minute PE sessions that

included 40-minute imaginal exposures, and 20 were randomized to 60-minute PE sessions that included 20-minute imaginal exposure (for details see the CONSORT Chart in Figure 1). A simple randomization procedure (computer-generated random numbers) was conducted prior to Session 3 by a senior psychiatrist with no clinical involvement in the study. Two patients dropped out of the study before randomization and one patient was withdrawn due to severe dissociation. One patient was withdrawn after randomization but before starting treatment because of severe, psychotic depression, and one dropped out during treatment; both were in the 90-minute condition. The latter patient was included in intention-to-treat (ITT) analyses. Table 1 presents the descriptive information of the study sample. Overall, the mean age of the participants was 36.87 years (SD = 13.40). Most participants were male (61.5%), single (46.2%;

FIGURE 1 Consolidated standards of reporting trials diagram of participant flow through the protocol. Note. PE = prolonged exposure; PTSD = posttraumatic distress disorder; IE = imaginal exposure.* Not in analyses. Please cite this article as: Nitsa Nacasch, et al., Are 60-Minute Prolonged Exposure Sessions With 20-Minute Imaginal Exposure to Traumatic Memories Sufficient to Successfully Treat ..., Behavior Therapy (2015), http://dx.doi.org/10.1016/j.beth.2014.12.002

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sixty vs. ninety minutes of prolonged exposure Table 1

Clinical Characteristics and Raw Scores of Symptoms and Trauma-Related Cognitions by Group Variable

60-min PE (n = 20)

Male Employed Marital status Single Married Divorced Index trauma type Single terror attack Combat Car accident Other Injury in trauma Comorbidity Major depressive disorder Anxiety disorder a

n

Age (years) Time since trauma (years) PSS-I Pre Post FU BDI Pre Post PTCI Pre Post

90-min PE (n = 19)

n

%

n

%

14 12

70.0 60.0

10 9

52.6 47.3

10 6 4

50.0 30.0 20.0

8 10 1

42.1 52.6 5.3

8 5 4 3 13

40.0 25.0 20.0 15.0 65.0

7 6 3 3 12

36.8 31.6 15.8 15.8 63.2

5 11

25.0 55.0

4 2

21.1 10.5

M

SD

n

M

SD

Cohen’s d

20 20

34.40 9.18

12.24 13.31

19 19

39.47 6.57

14.39 9.94

0.38 0.22

20 20 14

32.20 13.30 13.57

5.96 9.52 9.26

19 17 15

31.58 12.24 12.20

6.38 8.02 7.78

0.10 0.12 0.16

15 18

23.13 10.89

8.71 9.16

19 15

20.11 10.93

9.60 8.98

0.33 0.00

13 16

134.08 87.25

36.88 40.27

14 16

132.21 91.94

30.29 37.26

0.06 − 0.12

Note. PE = prolonged exposure; PSS-I = PTSD Symptoms–Interview version; Pre = pretreatment; Post = posttreatment; FU = follow-up; BDI = Beck Depressive Inventory; PTCI = Posttraumatic Cognitions Inventory. a Other than posttraumatic disorder.

41.0% married, 17.8% divorced), and employed (60.0%). The most prevalent index trauma (i.e., the traumatic event that participants endorsed as the most distressing and that was the focus of treatment) was terrorist attack (38.5%), followed by combat (28.2%), car accidents (17.9%), and sexual (childhood sexual abuse, rape) and nonsexual assault (15.4%). Psychiatric comorbidity was common, with 56.4% of the sample having at least one comorbid Axis I disorder. The most common comorbid conditions were current major depressive disorder (23.1%) and obsessive–compulsive disorder (23.1%). There were no significant differences between the two conditions in demographics, index trauma type, and clinical characteristics. However, participants in

the short-duration group (60-minute PE session) were more likely to have another comorbid anxiety disorder than those in the long-duration group: 90-minute PE session; 55.0% vs. 10.5%, χ 2 (1) = 4.50, p = .03. The study protocol was approved by the Sheba Medical Center Institutional Review Board.

design All eligible individuals were provided written informed consent after receiving a description of the study procedures. They were told that some participants will receive ten to fifteen 60-minute sessions with 20-minute imaginal exposure to their most upsetting traumatic memory and other participants will receive ten to fifteen 90-minute


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sessions with 40-minute imaginal exposure to their trauma memory. All participants first received two 90-minute sessions (for details, see below).

assessment Assessments of current PTSD symptoms were conducted by a master’s degree psychologist unaware of treatment assignment. Assessments were conducted before and after treatment. Outcome assessments included the interview of PTSD severity and selfreport measures described below. At 6-month follow-up, outcome via interview was assessed, but no self-report measures were administered. Psychologists who conducted assessments were uninvolved in treatment, and patients were asked not to disclose their treatment condition to the evaluators. Given that all patients received PE, discussion of the content of treatment would not make the evaluators aware of their treatment condition. measures Diagnostic Interview The Mini International Neuropsychiatric Interview 5.0 (MINI). The MINI (Sheehan et al., 1998) is a short, structured diagnostic interview that was used in the study to determine that the primary diagnosis was PTSD and to detect the presence of other Axis I disorders. The interview instrument is designed to cover 17 major Axis I disorders and has good correlation with the Structured Clinical Interview for the DSM-IV (First, Spitzer, Gibbon, & Williams, 1994). Primary Outcome Measure The Posttraumatic Symptom Scale-Interview (PSS-I). The PSS-I (Foa et al., 1993) is a semistructured interview that consists of 17 items corresponding to the DSM-IV PTSD symptoms. Items are rated on a scale of 0 (not at all) to 3 (five or more times a week/almost always) for combined frequency and severity in the past 2 weeks. Total scores range from 0 to 51 with higher scores indicating more severe PTSD symptoms; 10 to 15 is considered subclinical, 15 to 20 is mild to moderate, 21 to 25 is moderate, 26 to 30 is severe, and above 30 is very severe. Interrater reliability for PTSD diagnosis (r = .91) and overall severity (ICC = .97) have been shown to be excellent (for psychometric data see also Foa & Tolin, 2000; Powers, Gillihan, Rosenfield, Jerud, & Foa, 2012). Secondary Outcome Measures Beck Depression Inventory (BDI). The BDI (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961) is a 21-item self-report inventory designed to measure symptoms of depression, and addresses the intensity of cognitive, affective somatic and performancerelated symptoms with regard to depression. The

BDI is rated on a 4-point scale, with the total score ranging from 0 (no symptoms) to 63 (very severe); 14 to 19 is considered mild, 20 to 28 is moderate, and above 28 is considered severe. Internal consistency has been found to be high (α = 0.81–0.86; Beck, Steer, & Garbin, 1988). Scores on the BDI have been shown to correlate highly with clinician ratings of depression among female physical and sexual assault survivors (Foa et al., 1993). Posttraumatic Cognitions Inventory (PTCI). The PTCI (Foa, Ehlers, Clark, Tolin, & Orsillo, 1999) is a 36-item self-report inventory of trauma-related thoughts and beliefs that includes three subscales: negative cognitions about the self, negative cognitions about the world, and self-blame. Respondents rate the extent to which they agree or disagree with each statement on a scale of 1 (totally disagree) to 7 (totally agree). Total scores are calculated as the sum of all items, with higher scores indicating greater endorsement of negative cognitions. The total scale and self, world, and self-blame subscales have high internal consistency (.97, .97, .88, and .86, respectively) and good test–retest reliability (between .74 and .79 for 1 week in one sample, and between .80 and .85 for 3 weeks in a second sample; see also Zalta et al., 2013). The PTCI total score correlates strongly with measures of PTSD severity (.79) and depression (.75), and state- (.70) and trait anxiety (.75). Subjective Units of Distress (SUDs). The SUDs scale (Wolpe & Lazarus, 1966) is commonly used as a subjective verbal rating of discomfort. During the imaginal exposure, anxiety levels were monitored regularly using the SUDs on a 0–100 scale, with 0 indicating no feelings of discomfort at all and 100 the maximum level of discomfort. SUDs were obtained from the patients at the beginning of the imaginal exposure (SUDs start), every 5 minutes during the imaginal exposure, and at the end of the imaginal exposure (SUDs end).

therapists Therapy was delivered by eight therapists who were trained and supervised in PE. Therapists were two psychiatrists, two master’s degree psychologists, and four master’s degree social workers. Therapists participated in a 4-day workshop for PE conducted by the first and last authors and were supervised in a training case by an expert trainer who has taught PE and supervised PE cases for over 10 years (first author) prior to the start of the study. After the workshop, a supervision group was established. The group met once weekly throughout the study and supervision was conducted through viewing about 15% of all tapes to ensure adherence to the


sixty vs. ninety minutes of prolonged exposure treatment. Because all therapists conducted the same treatment (PE), had been using PE as their primary modality for treating PTSD for at least 5 years, and received weekly supervision conducted by an expert trainer, no formal adherence ratings were deemed necessary.

treatments PE was implemented according to the treatment manual (Foa et al., 2007). The same therapists delivered both types of treatment. Number of sessions of those who completed treatment ranged from 10 to 15. Treatment was determined to be complete when both the supervisor and therapist agreed that the patient’s self-reported symptoms of PTSD remained low and stable. This rationale was chosen on the basis of a prior finding that the majority of patients who did not reach at least 70% reduction in PTSD symptoms after Session 9 benefited from additional sessions (Foa et al., 2005). The overall mean number of sessions was 13.41 (SD = 2.39). The mean number of sessions for the short-duration group (M = 13.60, SD = 2.23) and long-duration group (M = 13.21, SD = 2.59) were similar, F(1, 37) = 0.25, p = .60. In practice, patients received either 10(24%), 12(8%), or 15(68%) sessions, and there was no difference between groups in the percentage who received 15 sessions, χ 2(1) = .21, p = .65. Prerandomization Phase: Sessions 1 and 2 This phase comprised two 90-minute sessions. Session 1 included presentation of treatment rationale, information gathering about trauma history, identification of the most disturbing trauma, and breathing retraining. Session 2 included education about trauma-related symptoms, rationale and construction of in vivo exposure hierarchy, and in vivo homework assignments. In vivo exposure involved confrontation of situations that were avoided either because they were trauma reminders or because they were similar to the traumatic event, and thus evoked fear that the traumatic event will occur again. Patients began to confront low-distresslevel situations and proceeded gradually to increasingly more distressing ones. Postrandomization Treatment Phase: Sessions 3–15 The treatment was identical in the two conditions with two differences: the short-duration group received 60-minute sessions with 20-minute imaginal exposure (in which they were asked to revisit the traumatic memory in their imagination and by recounting the story of the trauma aloud), whereas the long-duration group received 90-minute sessions with 40-minute imaginal exposure. All other aspects of the sessions were similar. Sessions 3–14 were

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conducted in a similar fashion: homework review, imaginal exposure for 20 or 40 minutes followed by a discussion of the imaginal exposure (processing), and assignment of in vivo exposure homework. Session 3 included rationale and initiation of imaginal exposure in which patients were asked to close their eyes and recount the traumatic memory aloud. The trauma narratives were audiotaped, and the patients were asked to listen to the tapes daily. During the first three imaginal exposures (Sessions 3– 5) patients were guided to repeatedly recount the traumatic memories from the beginning to the end within the allotted time (i.e., 20 or 40 minutes). In Sessions 6–14, patients were guided to repeatedly imagine and recount the most upsetting part of the trauma (i.e., “hot spots”) within the allotted time. The final session consisted of imaginal exposure to the entire trauma memory once, discussing the changes that occurred during treatment and the treatment component they found most helpful. Patients were asked to listen to a recording of the whole session (60 or 90 minutes) once per week and to listen to the imaginal exposure recordings (20 or 40 minutes) daily as homework. The treatment delivered in the trial followed the protocol used in previous RCTs for PE (e.g., Foa, Dancu, et al., 1999; Foa et al., 2005).

manipulation check One hundred and fifty-five sessions (36% of the total Sessions 3–15) were examined with regard to length of session and the length of the imaginal exposure in 21 randomly selected patients (11 in the long-duration group and 10 in the short-duration group). In the short-duration group, the mean length of sessions was 64 minutes and 43 seconds (SD = 4.70 minutes) and the mean length of imaginal exposure was 19 minutes and 27 seconds (SD = 1.64 minutes). In the long-duration group, the mean length of sessions was 87 minutes and 54 seconds (SD = 6.11 minutes) and the mean length of imaginal exposure was 38 minutes and 11 seconds (SD = 3.55 minutes). The mean length of sessions was significantly different between groups, F(1, 19) = 89.50, p b .001; the mean length of imaginal exposure was also significantly different between groups, F(1, 19) = 232.60, p b .01. statistical analyses For Hypothesis 1, our primary analysis, we used tests for noninferiority of the shorter-duration group relative to the longer-duration group (Blackwelder, 2004). This is done by examining whether the difference between the groups at posttreatment and at follow-up is smaller than a predetermined clinically reliable difference (i.e., the noninferiority


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margin [“delta”]). In contrast to traditional analyses, a significant effect in noninferiority tests suggests that outcome in the short-duration group is noninferior to the outcome of the long-duration group. We took two approaches to define delta. First, for each measure, the deltas were determined using the reliable change index developed by Jacobson and Truax (1991) and determined for PTSD studies by Devilly and Foa (2001). This index represents the difference between two assessments of a given scale, which is expected by chance, and is calculated using the data of the standard deviation of the scale and test–retest reliability. Using this formula and data from previous studies about our measures (Foa, Ehlers, et al., 1999; Oliver & Simmons, 1985; Powers et al., 2012), we determined that the reliable change would be 7 points for PSS-I, 4.5 points for BDI, and 22 points for PTCI. Our clinical experience suggests that these differences are also clinically significant. Second, to provide an “effect size” scale for assessing the size of the difference between the two groups, we calculated the Cohen’s d (Cohen, 1988) effect size between the two groups. While these “standardized effect sizes” have been criticized (Hoenig & Heisey, 2001; Lenth, 2001) as oversimplifying the process of sample size determination, they provide a useful scale for comparison of observed differences. For our purposes, we would regard effect sizes of less than d = 0.2 (i.e., less than a “small” effect) as supporting the hypothesis of noninferiority. We used a one-sided 95% confidence level and assumed a t distribution for analyses calculating the difference of the means of the two treatments and adding or subtracting the product of the pooled standard error by the critical t value needed for rejecting the null hypothesis. A priori power analyses for noninferiority studies (Julious, 2004) indicated that in order to achieve a power of .80, with a d value of 7 and a standard deviation of 8 on the PSS-I, a sample of 34 would be needed. 1 The data were also examined using multilevel linear models, which use all available responses for each subject, and so enable full ITT analyses (i.e., 60-minute PE: n = 20; 90-minute PE: n = 19). The models allowed an unstructured covariance matrix for the repeated measures within subjects, and treated visit as a categorical variable. Models were fitted for the PSS-I (using the pretreatment, posttreatment, and follow-up times) and for the BDI and PTCI (pre- and posttreatment only).

1 Note that the power analysis was calculated only for the main outcome measure, the PSS-I. The formula for power for effect sizes for noninferiority we used was n = f(α, β) × 2 × σ2/d2 and f(α, β) = [Φ−1(α) + Φ−1(β)]2.

To assess effect sizes of group differences, raw data were used to calculate standard Cohen’s d (Cohen, 1988) between groups using pooled variance. Model-based estimates of d were also calculated from estimates and standard errors in the mixedeffects repeated measures models. For Hypothesis 2, between-session and withinsession habituation were examined by recording subjective units of distress during imaginal exposures from each chart (cf. Jaycox et al., 1998; Kozak, Foa, & Steketee, 1988; van Minnen & Hagenaars, 2002). We used the first (Session 3) and last (the session before the final session) imaginal exposure sessions. Between-session habituation was calculated by subtracting the peak SUDs of the last session from the peak SUDs of Session 3 (cf. van Minnen & Foa, 2006). 2 In addition, for both of these imaginal exposure sessions, the degree of within-session habituation was computed by subtracting the end SUDs rating from the peak SUDs rating. For Hypothesis 3, change in PTSD symptoms and change in cognitions were calculated as residualized change scores from pre- to posttreatment in the PSS-I and PTCI, respectively, and Pearson correlation coefficients were used to measure within-person association between the two change scores.

Results noninferiority between shorter- and longer-duration groups See Table 1 for means, standard deviations, and effect sizes of the outcome measures. posttraumatic symptoms: pss-i For the PSS-I outcomes, tests of noninferiority suggested that the short-duration group was noninferior to the long-duration group with respect to the PSS-I score at posttreatment, t(35) = 2.10, p = .02, 95% CI of observed delta [− 3.88, 6.00], and at follow-up, t(27) = 1.85, p = .04, 95% CI [− 4.02, 6.77]; in each case, the upper endpoint of the confidence interval for the observed short minus long delta is less than our reliable change index, indicating noninferiority (see Figure 2). In addition, the observed effect sizes for differences between groups were d = 0.12 for the posttreatment point and d = 0.16 for follow-up, both in the “small effect” range of Cohen’s d scale. According to multilevel analyses on the PSS-I preto posttreatment, there was a main effect of time, F(1, 67.55) = 25.84, p b .001, suggesting a 2 When between-session habituation was defined as the change in peak SUDs from the third to fourth session, there was no significant difference between groups, t(27) = .52, p = .61, and correlations with outcomes were not significant, rs b .15, ps N .60.


sixty vs. ninety minutes of prolonged exposure

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group: t(37) = 10.88, p b .001; 19.78 unit decrease for longer-duration group: t(37) = 10.53, p b .001), with no significant change between posttreatment and follow-up for either group (p = 0.52 for shorterduration group, p = 0.80 for longer-duration group). Model-based versions of Cohen’s d (based on least squares means and standard errors) were 0.05, 0.08, and 0.17, for the pretreatment, posttreatment, and follow-up points, respectively. The differences for the posttreatment and follow-up points are similar to those found above by direct calculation, suggesting that missing data had little effect on the comparisons. As noted above, the effect sizes are all in the “small” range. In summary, results indicate that both groups had substantial reduction in PTSD symptoms, but that there were no apparent differences between groups at posttreatment or at follow-up.

depressive symptoms: bdi For the BDI, we found that tests of noninferiority approached significance when examining posttreatment outcomes, t(31) = 1.44, p = .08, 95% CI [− 5.43, 5.34], suggesting noninferiority. The observed Cohen’s d between groups was 0.00. Multilevel analysis of the BDI scores showed a main effect of time, F(1, 32.5) = 17.68, p b .01, and no significant Group × Time interaction effect, F(1, 32.4) = 1.99, p = .17. In summary, both groups demonstrated significant reduction in depression, with no apparent differences between groups.

FIGURE 2 Noninferiority margins and 95% confidence intervals (CI) for difference in outcomes between treatment conditions. Error bars indicate two-sided 95% CIs. The dashed lines at y = Δ indicate the minimum clinically reliable difference, or the noninferiority margin (Δ = 7 for PSS-I, Δ = 4.5 for BDI, Δ = 22 for PTCI). The vertical axis represents differences in PSS-I, BDI, and PTCI scores between conditions, with negative values indicating that 60-minute PE sessions resulted in greater improvement in outcome measures than 90-minute PE sessions. Note. PTSD = posttraumatic stress disorder; PSS-I = PTSD Symptoms–Interview version; BDI = Beck Depressive Inventory; PTCI = Posttraumatic Cognitions Inventory.

substantial decrease in PSS-I over time in both groups, but there was no Group × Time interaction, F(1, 68.22) = .12, p = .73, suggesting that there was not a significant differential change between the two groups. Results from post to follow-up did not show either a significant effect of time, F(1, 69.51) = 0.17, p = .68, or a Group × Time interaction effect, F(1, 68.97) = 0.17, p = .68. The acute time effect was due to significant decrease from pre- to posttreatment for each group (18.90 unit decrease for shorter-duration

change in cognitions: ptci Noninferiority tests suggested that the short-duration group was noninferior to the long-duration group with regard to PTSD-related negative cognitions level at posttreatment, t(30) = 2.17, p = .02, 95% CI [− 27.97, 18.59], Cohen d = − .12 (see Figure 2). Multilevel analysis showed no significant Group × Time interaction, F(1, 32) = .28, p = .60, a significant effect of time, F(1, 32) = 30.16, p b .0001, and no significant group effect F(1, 32) = 0.00, p = .95. Model-based Cohen’s d were .05 for pretreatment and –.06 for posttreatment. In summary, both groups demonstrated significant reductions in negative cognitions, with no apparent differences between groups. within- and between-session habituation Table 2 presents data on the within- and betweensession habituation (also see Figure 3). These data were collected from an outpatient clinic, so some cases did not include systematic collection of SUDs data as part of the clinical record and were therefore missing. As expected, patients in the long-duration group showed significantly more within-session


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Table 2

Within- and Between-Session Habituation Based on the SUDs Rating During First and Last Exposure Sessions Variable

60-min PE (n = 16)

Session 3 Peak SUDs End SUDs Within-session habituation Last session Peak SUDs End SUDs Within-session habituation Between-session habituation

90-min PE (n = 12)

t

p

Cohen’s d

M

SD

M

SD

78.63 71.44 7.19

20.07 20.46 6.32

84.58 58.33 26.25

11.96 16.83 20.68

0.91 1.81 3.09

.37 .08 .010

0.36 0.70 1.25

45.00 29.67 15.33 36.44

13.23 14.20 15.06 24.63

30.21 24.79 5.42 54.38

18.72 19.08 8.11 16.52

2.41 0.76 2.05 2.18

.02 .45 .05 .04

0.91 0.29 0.82 0.86

Note. PE = prolonged exposure; SUDs = subjective units of distress.

habituation in Session 3, t(27) = 3.50, p = .002, and a trend toward less within-session habituation in the last session, t(27) = 0.76, p = .05, than patients in the short-duration group. The long-duration group had significantly more between-session habituation than the short-duration group, t(27) = 2.18, p = .04.

correlations among process and outcome variables As expected, reduction in PSS-I symptoms was significantly correlated with reductions in negative cognitions as measured by the PTCI, r(25) = .41, p = .04. In addition, reduction in PSS-I was significantly related to greater between-session habituation, r(28) = − .40, p = .04, but not to greater early, r(28) = − .17, p = .39, or late, r(27) = .07, p = .72, within-session habituation. Reduction in PTCI was not correlated with either between-, r(18) = .01, p = .97, or early or later within-session habituation, r(18) = − .20, p = .44; r(17) = .12, p = .66, respectively. Furthermore, within- and between-session habituation were not

100.0 90.0 80.0 SUDs 70.0

60-min PE

60.0 50.0

90-min PE

40.0 30.0 20.0 10.0 0.0 peak first exposure

end first exposure

peak last exposure

end last exposure

Session

FIGURE 3 Subjective Units of Distress (SUDs) scale scores during first and last imaginal exposures for completers in 60- and 90-minute PE sessions. Note. PE = prolonged exposure.

correlated with each other, r(28) = .29, p = .13; r(27) = − .24, p = .22, respectively. When both between-session habituation and change in PTCI were simultaneously entered into a regression equation to predict reduction in PSS-I symptoms, the overall model approached significance, F(2, 15) = 2.59, p = .11, and there was no substantial change in the partial correlations. Both predictors approached significance (PTCI partial r = .28; between-session habituation partial r = − .45, p = .07), suggesting that cognitive change and betweensession habituation may be separate indicators of emotional processing in PE.

Discussion The hypothesis that 60-minute PE sessions with 20-minute imaginal exposures would yield noninferior outcomes to that of 90-minute sessions with 40-minute imaginal exposures was supported; no group differences were detected on PTSD symptoms, depression, and trauma-related cognitions, and noninferiority tests were either significant or close to significant. Our finding, using an RCT design, that both the long- and short-duration PE result in similar outcomes is consistent with van Minnen and Foa’s (2006) findings from a nonrandomized sample of 92 patients. Together, these two studies suggest that duration of the PE sessions and the imaginal exposure can be considerably shortened without sacrificing the benefit patients derive from treatment. In fact, in the present study the imaginal exposure was further shortened from van Minnen and Foa’s 30- to 20-minute imaginal exposure. By greatly reducing the duration of the imaginal exposure, we were able to address successfully the PE treatment components approximately within the 1-hour “standard” treatment session duration (after a thorough prerandomization 2- to 3-hour assessment, which was not included in time calculations of the treatment). This


sixty vs. ninety minutes of prolonged exposure adaptation renders the treatment less burdensome for both patients and therapists and more applicable to community clinical settings that are required to follow the standard session duration regulated by reimbursement policy. The current findings should be replicated in larger, more diverse populations to determine the generalizability of the results. Notably, one should not interpret the current findings to suggest that imaginal exposure shorter than 20 minutes will also yield a successful outcome. The efficacy of briefer exposure sessions (e.g., less than 20 minutes) is unknown until empirically studied. As hypothesized, 40-minute imaginal exposures resulted in greater within-session habituation than 20-minute exposures. In addition, consistent with van Minnen and Foa’s (2006) findings, we detected a significant relationship between PTSD symptom change and between-session habituation. Contrary to our hypothesis, however, 40-minute imaginal exposures resulted in greater between-session habituation than 20-minute exposures. This finding is somewhat different from that of van Minnen and Foa’s study, in which within-session but not betweensession habituation was greater in the 60-minute than in the 30-minute imaginal exposures. This inconsistency may be due to the differences in the duration of imaginal exposures in the two studies: 60 versus 40 minutes and 30 versus 20 minutes. In the present study the long-duration group showed substantial between-session habituation (M = 54.38 SUDs), which was significantly greater than that of the short-duration group (M = 36.44 SUDs). In contrast, in the van Minnen and Foa study, between-session habituation did not differ between the long- and short-duration groups (Ms = 20.2 and 21.1, respectively). This may suggest that a minimal amount of between-session habituation is required for symptom reduction, and that any gains beyond this minimum are only partially contributing to emotional processing and outcomes. In further support of this interpretation we found that while both the 20- and 40-minute imaginal exposure groups had maximum between-session habituation levels of over 80 SUDs, the 20-minute group included a significant proportion of patients (7/16) whose level of between-session habituation was lower than any of the patients in the 40-minute group. Despite this difference, the overall relationship of symptom reduction and betweensession habituation was similar in both groups. This further supports the suggestion that between-session habituation is related to outcome, but is not a very strong indicator (Foa et al., 2006). Notably, the variance in outcome accounted for by betweensession habituation and outcome was 16%, which allows for many other factors to contribute to symptom improvement.

11

The present study showed that PE resulted in a clinically significant reduction in explicit traumarelated negative cognitions that the world is extremely dangerous and that one is extremely incompetent, with similar reductions in both groups. We also found a significant correlation between change in negative cognitions and change in PTSD symptom severity. Our results are consistent with prior research and replicate Foa and Rauch’s (2004) study that found significant correlations between reduction in negative cognitions and reduction in PTSD symptoms. In a further study examining the role of cognitions in ameliorating PTSD via PE, McLean, Su, and Foa (2015) found that reduction in negative cognitions mediated symptom reduction in PE. Similarly, Zalta et al. (2013) found that reduction in trauma-related negative cognitions preceded reduction of PTSD symptom severity. Taken together, these findings, along with those of other studies, support EPT hypotheses that erroneous cognitions about the self and the world underlie PTSD and that modification of these cognitions is a potential mechanism of PE (Foa & Cahill, 2001). Future studies should consider use of measures of cognitions that are less biased by demand characteristics such as implicit measures or reaction time paradigms. It is important to note that 20 minutes of imaginal exposure was sufficient for most patients to recount the traumatic memory at least once, and that during the 40-minute imaginal exposure patients recounted their trauma two to three times. The findings that patients who recounted their traumatic memory for 20 minutes experience the same reduction in trauma-related negative cognitions as those who recounted it for 40 minutes suggest that recounting the traumatic memory once in each session (and then listening to the audiotapes of their recounting as homework) is sufficient for many patients to disconfirm their erroneous beliefs that engaging with the traumatic memory (rather than avoiding it) would result in them “falling apart” during such engagement. This experience allows the changing of patients’ negative cognitions about themselves. Interestingly, although the 90-minute PE group received twice as much imaginal exposure time compared with the 60-minute PE group, the number of sessions to reach criteria for treatment completion was the same in both conditions. This suggests that more imaginal exposure time does not expedite symptom reduction. Otherwise, participants in the 90-minute PE group would have completed treatment earlier than the 60-minute group. Future studies should examine this issue further by collecting a measure of session-by-session PTSD symptom severity.


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nacasch et al.

limitations Some caveats of our study should be recognized while interpreting the current findings. First, the sample size was small and the study should be replicated with a larger sample. Second, participants were randomized prior to Session 3 rather than before the beginning of treatment. Although the differences in duration of treatment sessions and imaginal exposures started after the randomization, the possible influence of the fact that the first two sessions were equivalent in both groups on the current findings remains unknown. It is possible that if therapists wish to remain within 60 minutes for the introductory sessions, it may require three, rather than two, sessions prior to starting imaginal exposures. Indeed, three introductory sessions were used in an uncontrolled study of PE in the Veterans Administration in the United States (Eftekhari et al., 2013). In general, therapists may have to be more efficient with time during 60-minute sessions than 90-minute sessions. Third, the psychometric properties of the study measures (e.g., interrater reliability and percentage agreement of the diagnosis) and therapist adherence to protocol were not evaluated in the current study. Fourth, homework compliance was not measured, and could have differed between groups. Fifth, the sample was relatively homogeneous in terms of gender, ethnicity, and traumas. Taken together with van Minnen and Foa (2006), however, these results may hold across populations and cultures, but more data should be collected on this. Sixth, no data on trauma severity was collected. Perhaps shorter sessions are insufficient to address the treatment needs of those exposed to more severe trauma events. However, the group did not differ in the number of participants who were injured during the trauma, a common indicator of trauma severity. In addition, data were not available to examine the session-by-session change in between- or within-session habituation and their relationships with symptom change, and the data on within- and between-session habituation were partial due to therapists not recording these data systematically. This left these analyses with moderate power (approximately .65, below the desired Cohen’s d of .80). The lack of systematic collection of SUDs could have made the data less reliable and influenced the results. Finally, it should be noted that in this study, as well as in previous studies, a selfreport inventory was used to measure negative cognitions.

Conclusions In sum, 20-minute imaginal exposure within 60-minute sessions yielded noninferior outcomes in PTSD symptoms and posttraumatic negative

cognitions at posttreatment and follow-up to the 40-minute imaginal exposures and 90-minute sessions. The current study also showed that longer imaginal exposures resulted in greater within- and between-session habituation than shorter exposures. However, because both conditions exhibited similar efficacy, it can be reasoned that maximal within- and between-session habituation may not be necessary conditions for successful PE, although some level of between-session habituation is related to outcomes (cf. Foa et al., 2006). In contrast, negative cognitions and PTSD symptom severity decreased similarly in the long- and short-treatment-duration groups and were correlated with reduction of PTSD symptoms severity. These findings support EPT’s supposition that withinand between-session habituation are indicators of emotional processing, whereas reduction of negative, erroneous cognitions is, as noted above, a potential mechanism underlying emotional processing and the resultant symptom reduction. Indeed, change in negative cognitions and between-session habituation—but not within-session habituation— was correlated with treatment outcome and none of the three were correlated with one another.

Disclosure Statement for Authors All authors report no financial relationships with commercial interests. Conflict of Interest Statement The authors declare that there are no conflicts of interest.

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