Inclusion and exclusion criteria in randomized controlled trials of psychotherapy for PTSD.

Inclusion and Exclusion Criteria in Randomized Controlled Trials of Psychotherapy for PTSD Objective. Posttraumatic stress disorder (PTSD) is a prevalent and often disabling condition. Fortunately, effective psychological treatments for PTSD are available. However, research indicates that these treatments may be underutilized in clinical practice. One reason for this underutilization may be clinicians’ unwarranted exclusion of patients from these treatments based on their understanding of exclusion criteria used in clinical trials of psychological treatments for PTSD. There is no comprehensive and up-to-date review of inclusion and exclusion criteria used in randomized clinical trials (RCTs) of psychological treatments for PTSD. Therefore, our objective was to better understand how patients were excluded from such RCTs in order to provide guidance to clinicians regarding clinical populations likely to benefit from these treatments. Methods. We conducted a comprehensive literature review of RCTs of psychological treatments for PTSD from January 1, 1980 through April 1, 2012. We categorized these clinical trials according to the types of psychotherapy discussed in the major guidelines for treatment of PTSD and reviewed all treatments that were studied in at least two RCTs (N = 64 published studies with 75 intervention arms since some studies compared two or more interventions). We abstracted and tabulated information concerning exclusion criteria for each type of psychotherapy for PTSD. Results. We identified multiple RCTs of cognitive behavioral therapy (n = 56), eye movement desensitization and reprocessing (n = 11), and group psychotherapy (n = 8) for PTSD. The most common exclusions were psychosis, substance abuse and dependence, bipolar disorder, and suicidal ideation. Clinical trials varied in how stringently these criteria were applied. It is important to note that no exclusion criterion was used in all studies and there was at least one study of each type of therapy that included patients from each of the commonly excluded groups. A paucity of evidence exists concerning the treatment of patients with PTSD and four comorbidities: alcohol and substance abuse or dependence

Journal of Psychiatric Practice Vol. 20, No. 1

JULIA M. RONCONI, MS, APRN BRIAN SHINER, MD, MPH BRADLEY V. WATTS, MD, MPH

with current use, current psychosis, current mania, and suicidal ideation with current intent. Conclusions. Psychological treatments for PTSD have been studied in broad and representative clinical populations. It appears that more liberal use of these treatments regardless of comorbidities is warranted. (Journal of Psychiatric Practice 2014;20:25–37) KEY WORDS: posttraumatic stress disorder (PTSD), psychological treatments, randomized clinical trials, exclusion criteria

Posttraumatic stress disorder (PTSD) is a debilitating condition that follows exposure to a traumatic event. Patients with PTSD experience three categories of symptoms: re-experiencing, avoidance and numbing, and hyperarousal. Patients make great efforts to avoid reminders of their trauma but are often thwarted by intrusive recollections of the event; such avoidance and re-experiencing significantly interfere with daily functioning. PTSD has an estimated lifetime prevalence of 7.8% in the United States.1 Evidence-based treatments for PTSD have been developed and include both pharmacotherapy and psychotherapy.2,3 Treatment guidelines and expert recommendations differ slightly in their recommendations for pharmacotherapy.4,5 However, all guidelines RONCONI: White River Junction Veterans Affairs Medical Center, White River Junction, VT; SHINER: White River Junction Veterans Affairs Medical Center and Geisel School of Medicine at Dartmouth, Hanover, NH; WATTS: Geisel School of Medicine at Dartmouth and VA National Center for Patient Safety, White River Junction, VT. Copyright ©2014 Lippincott Williams & Wilkins Inc. Please send correspondence to: Brian Shiner, MD, MPH, VA Medical Center, 215 North Main Street (11Q), White River Junction VT 05009. [email protected] Support: Dr. Shiner’s time was supported by the VA New England Early Career Development Award Program (V1CDA2010-03). Disclosure: None Disclaimer: This is the work of the authors and does not necessarily represent the position of the Department of Veterans Affairs. DOI: 10.1097/01.pra.0000442936.23457.5b

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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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PATIENT SELECTION IN RANDOMIZED CONTROLLED TRIALS OF PSYCHOTHERAPY FOR PTSD

strongly support the use of specific evidence-based psychological treatments for adults with PTSD.6 Despite the endorsement of evidence-based psychotherapies (EBT) for the treatment of PTSD, they have been shown to be underutilized in clinical practice.7,8 Four studies examined the use of psychotherapy for PTSD within the U.S. Department of Veterans Affairs (VA) and found that few patients attend a sufficient number of sessions to receive EBTs for PTSD.9–12 In addition, few VA psychotherapists appear to be choosing EBTs as an initial approach in treating PTSD.13 Reasons for the underutilization of EBTs for PTSD are unclear. Some authors have examined patient preferences for treatment as a barrier to the delivery of EBT for PTSD.14 Others have attributed underutilization to lack of clinician training in EBTs.15 However, neither of these factors has been validated in the literature. Recent evidence suggests that many patients prefer psychotherapy to pharmacotherapy.16–18 In addition, even with adequate training, clinicians tend not to choose EBT for their patients,15 suggesting that other factors are also barriers to the dissemination of EBT for PTSD. Clinician factors in the selection of PTSD treatment are an understudied area. Surveys have found that clinicians often employ exclusion criteria when selecting treatment for PTSD in routine practice, particularly when patients present with comorbid psychiatric disorders and complicating life circumstances.19 Although there is little consensus among clinicians regarding exclusion criteria for EBTs in their practices, many clinicians have endorsed comorbid psychosis, suicidality, substance abuse and dependence, unresolved life crises, poor physical health, personality disorders, dissociation, comorbid anxiety disorders, and neuropsychological difficulties as contraindications to EBTs for PTSD.15,20 Furthermore, many clinicians believe that study populations in randomized control trials (RCTs) do not represent clinical populations. Some authors have hypothesized that, by employing informal exclusion criteria, clinicians believe they are mimicking the inclusion and exclusion criteria used in psychotherapy RCTs.19,21 However, it also appears that clinician beliefs about exclusions are not consistent with the research evidence.15,19,21 These exclusions may severely limit patient access to treatment. For example, when clinician beliefs about contraindications from the survey by Litz et al.20 were theoret-

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ically applied to an outpatient population of Veterans, only 27% of the patients would have been eligible for exposure therapy.22 To better inform clinical decision-making, we sought to review the RCTs for PTSD psychotherapies and examine their exclusion criteria. Three earlier studies have conducted similar reviews of such RCTs, but they were not ideal for this application. Stirman et al. examined RTCs for 10 mental health disorders, including 4 RCTs of psychotherapy for PTSD with study dates ranging from 1989–1991.23 The authors concluded that PTSD studies most often excluded patients for insufficient PTSD severity or for demographic criteria such as Veteran status. However, due to the small number of studies reviewed and the lack of inclusion of recent RCTs, the study does not provide adequate guidance for clinicians in current practice. Stirman later examined the applicability of evidence from PTSD RCTs to a Veteran population in a more comprehensive and updated review.24 She found that most Veterans would have been eligible for multiple studies and identified psychosis, substance use disorders, and bipolar disorder as the exclusion criteria most likely to restrict veterans from inclusion in PTSD RCTs. However, the study did not consider RTCs in nonVeteran study populations. Spinazzola et al. examined inclusion and exclusion criteria in the International Society for Traumatic Stress Studies (ISTSS) Gold Standard Efficacy Studies.25 They found that comorbid psychosis, substance use disorders, severe psychopathology, and organic mental illness were most often listed as exclusion criteria in studies cited in the gold standard guidelines. However, the studies examined were published before 2000. No recent comprehensive review of patient selection in RCTs for PTSD psychotherapy that includes all potential demographic populations and RCTs exists. During the years since the last review, more emphasis has been placed on studies that broaden inclusion criteria.19 The purpose of our study was to review all available RCTs for PTSD psychotherapies published between 1980 and March 2012 in order to compile data on exclusion criteria. We hypothesized that no patient characteristic has been completely excluded from all RCTs and that RCTs in general are inclusive of clinical populations. We also hypothesized that practicing clinicians employ stricter exclusion criteria than were utilized in RCTs of PTSD




psychotherapies. Our goal is to better inform practicing clinicians about the known data on patient selection for psychotherapeutic treatment of PTSD and to highlight areas needing additional study. Our hope is that this information will help clinicians more confidently offer needed EBTs to patients with PTSD. Methods We searched PubMed, Medline, the Published International Literature on Traumatic Stress (PILOTS) database, PsycINFO, and the Cochrane databases for articles published between January 1, 1980 and April 1, 2012. For PubMed and Medline, we used the search terms post-traumatic stress disorders, posttraumatic stress disorder, PTSD, combat disorders, and stress disorders, post-traumatic. We limited the results to articles indexed by a thesaurus term as a “clinical trial” or those that included the terms treatment trial, randomized, or controlled trial in their title or abstract. For PILOTS, a database focused exclusively on traumatic stress, we used the thesaurus terms “clinical trial” and “adults” and limited our search to English language publications since 1980. We searched PsychINFO by cross referencing the terms post traumatic stress disorder (PTSD) and clinical trial and treatment. We searched the entire Cochrane database by hand. We also systematically reviewed references of all included studies as well as previous review articles and meta-analyses in order to locate additional references. Studies that were included in our review had to 1) be a clinical trial in which participants were randomly assigned to one or more active treatments and to a control group; 2) involve only adult participants (age 18 years and older), all of whom met PTSD diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders III, III-revised, or IV (DSM-III, DSM-III-R, DSM-IV, DSM-IV-TR); and 3) test the use of a psychotherapy. We reviewed each included study and abstracted exclusion and inclusion criteria. When the exclusion criteria were vague, we scored the study as using the most restrictive criteria. For example, for one study that identified “depression” as an exclusion criterion, we coded it as excluding both current depression and history of depression. We aggregated similar exclusion criteria. For example, data on bipolar disorder and mania were combined. Complicating life circumstance was combined with presence of abusive rela-


tionships and grief. After we had reviewed all of the identified studies, we categorized the data by type of psychotherapy and tallied the number and percent of studies that used a given criterion. Our groupings of types of psychotherapy were based on those used in recent practice guidelines for the treatment of PTSD.2,4,26 We excluded singleton studies—those studies that were the only RCT examining a given type of psychotherapy for PTSD. We then tallied the most frequently used inclusion and exclusion criteria for each type of psychotherapy. Results We found 63 published articles describing clinical trials of psychotherapy that met the eligibility criteria for our study.27–89 These studies included 75 intervention arms (11 studies34,38,44,48,50,62,66,75,77,79,88 compared two or more different types of interventions). Types of psychotherapy represented in more than one study included cognitive-behavioral therapies (primarily cognitive, primarily exposure, and mixed cognitive/exposure subtypes), eye movement desensitization and reprocessing (EMDR), and group therapy. Types of psychotherapy represented in excluded singleton studies included psychodynamic therapy, hypnotherapy, biofeedback, and self-help. Exclusion criteria used in more than 20% of studies included depression, psychosis, substance abuse, substance dependence, bipolar disorder, suicidal ideation, and recent changes to psychotropic medications (Table 1). The full list of studies and commonly used exclusion criteria is provided in Appendix 1. No exclusion criterion was used in all studies and there was at least one study of each type of therapy that included patients from each of the commonly excluded groups. The most commonly utilized exclusion criteria were psychosis, substance dependence, bipolar disorder, and suicidal ideation. However, application of specific exclusion criteria varied. Some studies excluded patients with histories of a particular criterion while others excluded only current conditions. Therefore we also examined the stringency of individual exclusion criteria (Table 2). Most of the RCTs did not exclude patients with histories of substance dependence, bipolar disorder, and suicidal ideation; almost half did not exclude patients with a history of psychosis. Instead, the studies commonly excluded only patients with current symptoms of these conditions. In the case of depression and suici-

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58.7% (44)

58.7% (44)

41.3% (31)

dal ideation, current severity was an important factor; studies generally only excluded patients with depression if their symptoms were severe and patients with suicidal ideation only if they reported intent. In the case of substance abuse and dependence, most studies allowed patients with 3–6 months of abstinence to participate and many studies had no exclusions. With regard to less frequently used exclusion criteria, other anxiety disorders (4.0%), personality disorders (13.3%), and complicating life circumstance (12.0%) were seldom identified as exclusion criteria. Neurologic impairment was listed as a study exclusion criterion in inconsistent ways. For example severe brain lesions requiring treatment,72 organic mental disorders,51,63 organic brain disease,66 organic mental illness,48 current organic mental dysfunction/history of epilepsy,38 organic psychiatric disorders,67 and organic brain syndrome34 were identified but lacked clear descriptions. These studies likely excluded patients with advanced dementia but, without clarity regarding their classification, we were unable to provide an accurate assessment of their exclusion in clinical trials. We also attempted to identify the number of patients enrolled in RCTs for PTSD with each comorbid condition. However, only 5 of the RTCs provided diagnostic information about their study populations, although most of them included age, gender, work history, socioeconomic information, and type of trauma as demographic statistics. Discussion EMDR: eye movement desensitization and processing

44.0% (33) 28.0% (21) All studies (n = 75)

90.7% (68)

72.0% (54)

12.5% (1) 50.0% (4) 50.0% (4) 62.5% (5) 87.5% (7) 25.0% (2) Group (n = 8)

36.4% (4) 36.4% (4)

exposure (n = 13)

Mixed cognitive and

EMDR (n = 11)

90.9% (10)

75.0% (6)

27.3% (3) 63.6% (7) 54.5% (6)

61.5% (8) 53.8% (7) 84.6% (11) 53.8% (7)

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30.8% (4)

100.0% (13)

63.6% (7)

38.5% (5)

46.7% (14)

61.5% (8) 61.5% (8)

56.7% (17) 63.3% (19)

61.5% (8) 69.2% (9)

70.0% (21)

53.8% (7)

33.3% (10)

76.9% (10)

Primarily exposure (n = 30)

93.3% (28)

30.7% (4)

23.3% (7)

Primarily cognitive (n = 13)

Cognitive-behavioral

Therapy

Percentage of studies excluding patients with the following conditions (n) Substance Substance Bipolar Suicidal Depression Psychosis abuse dependence disorder ideation

Table 1. Patients excluded in PTSD psychotherapy randomized controlled trials by covariate

Recent psychotropic changes


We surveyed RCTs that evaluated psychotherapies for PTSD with regard to their inclusion and exclusion criteria and found only 7 exclusion criteria that were used in more than 20% of the clinical trials. None of these 7 exclusion criteria was included in all of the studies; in other words, some research has been done in patients with PTSD that included all of the factors and comorbid diagnoses described in the 7 most common exclusion criteria. In addition, some studies specifically addressed patient populations that have commonly been excluded from RCTs of psychotherapy for PTSD, such as individuals with psychotic disorders.70 Thus, RCTs evaluating psychotherapies for PTSD are more inclusive than clinicians appear to believe. One potential limitation in our findings is that lack of exclusion from a study is not synonymous




Table 2. Stringency of exclusion criteria (N = 75) Percentage of studies utilizing each degree of exclusion (n) Most restrictive Least restrictive

Criteria Depression Psychosis

History 0% (0)

Current 1.3% (1)

History 50.7% (38)

Current severe 26.7% (20)

No exclusions 72.0% (54)

Current 40.0% (30)


History 2.7%(2)

3–6 months abstinence 9.3% (7)

< 1 month abstinence 6.7% (5)

Current use 25.3% (19)


Substance dependence

History 16.0% (12)

3–6 months abstinence 16.0% (12)

< 1 month abstinence 6.7% (5)

Current use 33.3% (25)


Bipolar disorder

History 26.7% (20)

Suicidal ideation

History 1.3% (1)

Substance abuse

Recent psychotropic ehanges

Any use 2.7% (2)

Current mania 32.0% (24) Current 13.3% (10) 3–6 months stable 14.7% (11)

with inclusion in a study. That certain comorbidities and factors were not systematically excluded from study populations does not necessarily guarantee that they were included in the study populations. While no study exclusion criterion was included in all the identified RCTs, we were unable to determine the frequency with which inclusive studies enrolled patients with particular comorbid conditions. With this limitation in mind, our study suggests that psychotherapy for PTSD has likely been studied in a broad and representative group of patients, so that current evidence regarding psychotherapy for PTSD would appear to be applicable to clinical populations. Patients with the most common PTSD comorbidities1 have been eligible for many RCTs of psychotherapy for PTSD (Table 3). Inclusiveness is even greater when the strictness of each exclusion criterion is considered. For example, while many RTCs excluded patients with severe depression (26.7%), they did not exclude patients with less severe depression. Most depressed patients (73%) present with mild or moderate depression,90 suggesting that only a small percentage of patients have been excluded from RCTs for PTSD based on depression. Only 3 of the studies we identified excluded patients with other anxiety disorders, suggesting a wide body of evidence



Current with intent 44.0% (33) 2 months stable 17.3% (13)


Current instability 6.7% (5)


for the efficacy of psychotherapy for PTSD in clinical populations with multiple anxiety disorders. Substance abuse and dependence are highly prevalent among patients with PTSD. Fortunately, patients with these conditions have frequently been permitted to participate in RCTs of psychotherapy for PTSD; 56.0% of RCTs placed no exclusions on substance abuse while 28.0% placed no exclusions on substance dependence. When surveyed about treating comorbid substance use disorders with psychotherapy, clinicians expressed uncertainty regarding the length of abstinence needed before trauma work can begin, whether or not trauma work should be discontinued in the presence of relapse, and whether or not patients with significantly decreased substance use can receive trauma therapy.91 Published studies did not systematically exclude patients who abused or were dependent upon substances. Based on these data, clinicians have a strong evidence base for delivery of EBTs for PTSD in patients with dual diagnoses. Two studies have assessed clinicians’ beliefs about contraindications to EBT for PTSD.15,20 Among the types of psychotherapies we reviewed, practice guidelines give their highest level of recommendation to the cognitive-behavioral therapies and EMDR for the

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Table 3. Comparison of PTSD comorbidities and RCT inclusion criteria

PTSD comorbidity

% of RCTs Incidence* permitting Men Women condition

Depression

47.9%

48.5%

76.0%

Mania

11.7%

5.7%

40.0%

Anxiety disorders Generalized anxiety disorder Simple phobia Social phobia Alcohol abuse and dependence Alcohol abuse Alcohol dependence Drug abuse and dependence Drug abuse Drug dependence

97.4% 16.8% 31.4% 27.6%

15.0% 29.0% 28.4%

51.9%

27.9% 60.1% 34.6%

34.5%

26.9% 58.7% 30.7%

*Kessler et al. 19951 RCT: randomized controlled trial

treatment of PTSD.2,4,26 Therefore, we will consider these EBTs for the purposes of this discussion. Becker et al.15 found that clinicians often viewed comorbid psychotic disorders, severe suicidality, homicidality, dissociation, and comorbid anxiety disorders as contraindications to exposure based therapies. In another survey, clinicians identified comorbid psychotic disorders, history of suicidality, substance abuse and dependence, unresolved life crises, poor physical health, and personality disorders as reasons to exclude patients from exposure therapies.20 Table 4 compares clinicians’ beliefs as assessed by these studies to our findings on the exclusion criteria used in RCTs of EBTs for PTSD. Notably, clinicians tend to be more conservative in their administration of EBTs for PTSD than RCTs were in studying the therapies, especially in the areas of suicidality, unresolved life crises, personality disorders, dissociation, homicidality, and comorbid anxiety disorders. Clinicians appear to be misinformed about the evidence base and thus are at risk of not providing EBTs for some patients with PTSD for whom evidence indicates that such treatments can be efficacious.

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A few criteria warrant more discussion. The most commonly excluded comorbid conditions in RCTs were psychosis, suicidal ideation, bipolar disorder, and substance use or dependence. In the case of psychosis and bipolar disorder, clinicians are uncertain how they should practice when these comorbid conditions are present and worry that trauma-focused therapies may exacerbate illness in seriously mentally ill populations.92 Mueser et al. compared cognitivebehavioral therapy for PTSD with treatment as usual in 108 clients who had PTSD and either major mood disorder or schizophrenia or schizoaffective disorder; this is the only RCT to date that has directly studied this population.70 They showed that clients with severe mental illness and PTSD can benefit from cognitive-behavioral therapy, despite severe symptoms, suicidal thinking, psychosis, and vulnerability to hospitalizations. Others researchers have studied psychotherapies for PTSD in populations with severe mental illness utilizing less stringent study designs that did not meet our inclusion criteria,93–95 and all reported favorable outcomes. Grubaugh et al. extensively reviewed the literature on PTSD and severe mental illness, highlighting the high incidence of PTSD among persons with severe mental illness.96 RCTs often excluded patients with suicidal ideation with intent, but were much less likely to exclude patients with suicidal ideation without suicidal intent or with histories of suicidal ideation (Table 2). Our review indicates that clinicians can offer EBTs for PTSD to patients with severe mental illness and suicidal ideation in most instances, with evidence supporting benefit to this patient population. Although RCTs for PTSD psychotherapies do not frequently list complicating life circumstance as exclusion criteria, a significant percentage of clinicians believe that patients undergoing life stress should wait before receiving EBT for PTSD.20,97 However, our review does not lend empirical support for this practice, since life circumstances are seldom listed as exclusion criteria in RCTs for PTSD. The most common use of complicating life circumstances was in study populations in which PTSD psychotherapies were being used with sexual assault victims.50,61,67,77 In these studies, patients in current abusive relationships were excluded. However, study populations often included participants in chaotic life circumstances. For example, Bichescu et al.32 and Neuner et al.72,74 used PTSD psychotherapies in the treatment of refugees. In the case of Neuner’s studies,




the work was conducted in refugee Table 4. Comparison of clinician-identified contraindications camps where the participants had to PTSD psychotherapies and exclusion criteria used recently been exposed to complex trauin randomized controlled trials ma and were in an unstable and uncerClinician-identified RCTs utilizing tain living environment. Even in these contraindications to Litz Becker exclusion conditions, the authors measured benePTSD psychotherapies et al.20 et al.15* criterion fit from their treatments. The evidence suggests both that patients can benefit Comorbid psychotic disorder 91% 80.5% 90.7% from EBTs for PTSD regardless of their History of suicidality 58% 1.3% current life circumstance and that cliniSevere suicidality 82% 44.0% cians can comfortably offer the treatments given evidence of their efficacy. Substance dependence 27% 72.0% A final area of discussion is medical Unresolved life crisis 18% 12.0% comorbidity. Medical comorbidity is Poor physical health 18% 14.6% most often discussed in the context of exposure therapies and cardiac comorPersonality disorder 33% 13.3% bidity. The concern for the clinician is Dissociation 51% 13.3% that increased sympathetic activation elicited by the recall of traumatic memHomicidality 71.5% 6.6% ories could destabilize a compromised Comorbid anxiety disorder 32% 4.0% cardiovascular system. Our review *Average of study groups reported found a small percentage of studies Litz et al.20 and Becker et al.15 were studies that assessed clinicians’ beliefs (14.6%) that excluded patients based about contraindications to evidence-based psychotherapies for PTSD. upon medical comorbidities. Recently, Shemesh et al.98 specifically studied tional Society for Traumatic Stress Studies, second edithe safety of exposure therapy in patients with cartion. New York: Guilford Press; 2008. diovascular illness and found no inherent health3. Institute of Medicine (Berg AO, Breslau N, Goodman SN, et al. Committee on Treatment for Posttraumatic Stress related risks. Medical comorbidity is another area in Disorder). Treatment of posttraumatic stress disorder: An which clinicians are supported by evidence when assessment of the evidence. Washington, DC: The National administering EBTs for PTSD. 4.

Conclusion Our study suggests that RTCs for PTSD psychotherapies demonstrate a broad evidence base for most clinical populations and that clinicians could be much more liberal in their use of EBTs. There are a few areas in which further study is needed—delivery of EBTs to patients with current substance abuse and dependence, current psychosis, current mania, and suicidal ideation with intent. In other common circumstances, however, clinicians have an evidence base for the use of EBTs in the clinical setting.

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EMDR

Primarily exposure

Primarily exposure

Primarily cognitive

Group

Mixed cognitive and exposure

Devilly38

Difede39

Difede40

Duffy41

Dunn42

Echeburua43

Primarily exposure

EMDR

Devilly38

Foa48

Primarily cognitive

Chard37


EMDR

Carlson36

Foa48

Primarily exposure

Bryant35

Primarily exposure

Primarily exposure

Bryant34

Feske47


Bryant34

Primarily exposure

Group

Brom33

Fecteau46

Primarily exposure

Bichescu32

Primarily cognitive

Primarily exposure

Beidel31

Group

Group

Beck30

Ehlers45

Primarily exposure

Basoglu29

Primarily cognitive

Primarily exposure

Basoglu28

Ehlers44

Primarily exposure

Asukai27

Ehlers44

Treatment group

Study (first author)

January 2014

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. None

None

Severe

Severe

Severe

Severe

Severe

None

None

None

None

None

Severe

Severe

None

None

None

None

None

None

None

Severe

None

Severe

Severe

Severe

Depression

Current

Current

History

Current

History

History

History

Current

History

None

History

Current

Current

Current

None

History

History

History

History

None

None

Current

Current

History

History

Current

Psychosis

None

None

None

Current

Current

Current

Current

Current

None

None

None

None

None

None

None

< 1 month abstinence

None

None

None

None

None


< 6 months abstinence

None

None

Current

Substance abuse

History

History

Current

Current

Current

Current

Current

Current

None

None


None

None

None



History

History

History

None

None



None

History

Current


Appendix 1: Patients excluded in each PTSD randomized controlled trial by covariate

Current

Current

None

Current

None

None

None

Current

History

None

History

Current

Current

Current

None

None

None

History

History

None

None

Current

Current

None

None

None

Bipolar disorder

With intent

With intent

Current

None

Severe

Severe

Severe

None

Current

None

With intent

None

With intent

With intent

None

None

Current

With intent

With intent

None

None

None

With intent

With intent

Current

With intent

Suicidal ideation

Stable < 3 months

Stable < 3 months

Current instability

None

None

None

None

None

None

None

None

Stable < 2 months

None

None

Stable < 3 months

None

None

None

None

None

None

None

None

Stable < 2 months

Stable < 2 months

None



35

36

January 2014


EMDR

Lee62

McDonagh67

Primarily cognitive

Kubany61

Primarily exposure

Group

Krupnick60

Primarily cognitive

Primarily cognitive

Kent59

Marks66

Primarily exposure

Keane58

Marks66

Primarily cognitive

Johnson57


EMDR

Jensen56

Marks66

Group

Hollifield55

EMDR


Hinton54

Marcus65


Hinton53


Primarily exposure

Hensel-Dittman52

Litz64


Gersons51


Primarily exposure

Foa50

Lindauer63


Foa50


Primarily exposure

Foa49

Lee62

Treatment group


Appendix 1: continued

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Severe

None

None

None

None

None

Current

None

None

None

None

None

None

None

Severe

None

None

None

None

Severe

None

None

Severe

Depression

Current

History

History

History

History

History

History

History

History

History

History

Current

None

Current

Current

Current

History

History

History

History

Current

Current

History

Psychosis


Current

Current

Current


None

History

None

None

Current


Current

None

None

None


Current

None

None

History

None

None

Current

Substance abuse


None

None

None


Current

History

History

History

Current


Current

None

None

None


Current

None

History

History

Current

Current

Current


Current

History

History

History

None

None

None

None

None

History

History

Current

None

Current

Current

None

None

None

None

None

Current

Current

History

Bipolar disorder

History

With intent

With intent

With intent

Current

Current

None

None

None

None

None

With intent

None

With intent

With intent

With intent

None

None

With intent

With intent

With intent

With intent

None

Suicidal ideation

None

Stable < 3 months

Stable < 3 months

Stable < 3 months

Current instability

None

Any use

None

None

Current instability

None

None

None

Stable < 1 month

None

None

None

None

None

Stable < 1 month

None

None

None





EMDR

Primarily exposure

Primarily exposure

Primarily exposure

Group

Primarily exposure

Rothbaum79

Rothbaum79

Rothbaum80

Schneier81

Schnurr82

Schnurr83

Group

EMDR

Rothbaum78

Zlotnick89

Primarily exposure

Resick77

Primarily exposure

Primarily cognitive

Resick77

EMDR

Primarily exposure

Ready76

Vaughan88


Power75

Vaughan88

EMDR

Power75

EMDR

Primarily exposure

Neuner74

van der Kolk87

Primarily exposure

Neuner73

Primarily exposure

Primarily exposure

Neuner72

Primarily cognitive

Primarily exposure

Nacasch71

Tarrier86

Primarily cognitive

Mueser70

Spence85

Primarily cognitive

Monson69

Primarily cognitive

Primarily exposure

McLay68

Schnyder84

Treatment group


Appendix 1: continued

January 2014

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. None

None

None

None

None

Severe

Severe

None

Severe

None

None

None

None

None

None

None

None

Severe

Severe

None

None

None

None

None

None

None

Depression

History

History

History

History

Current

Current

History

Current

History

Current

History

History

History

None

Current

Current

History

History

History

Current

History

Current

Current

None

Current

Current

Psychosis

Current

None

None

Current

Current

None


None

None


None

None

None

None

Current

Current

Inclusion and Exclusion Criteria in the Diagnosis of Femoroacetabular Impingement.

Should criteria for inclusion in cancer clinical trials be expanded?

exclusion criteria for total disc replacement.

Problems in the Descriptions of the Psychiatric Inclusion and Exclusion Criteria in Publications of Antidepressant Efficacy Trials: A Qualitative Review and Recommendations for Improved Clarity.

Process Interventions for Vaccine Injections: Systematic Review of Randomized Controlled Trials and Quasi-Randomized Controlled Trials.

Psychotherapy for PTSD: neuroimaging of recovery processes.

Selection of patients for randomized controlled trials: implications of wide or narrow eligibility criteria.

A systematic appraisal of allegiance effect in randomized controlled trials of psychotherapy.

Treatment of severe hospital-acquired and ventilator-associated pneumonia: a systematic review of inclusion and judgment criteria used in randomized controlled trials.

Randomized controlled trials.

Expectations of Social Inclusion and Exclusion.

Procedural and Physical Interventions for Vaccine Injections: Systematic Review of Randomized Controlled Trials and Quasi-Randomized Controlled Trials.

Interventions for Individuals With High Levels of Needle Fear: Systematic Review of Randomized Controlled Trials and Quasi-Randomized Controlled Trials.

Unusual exclusion criteria.

Justification of exclusion criteria was underreported in a review of cardiovascular trials.

Evaluation criteria and psychotherapy research.

Augmentation of Evidence-Based Psychotherapy for PTSD With Cognitive Enhancers.

Outcome criteria in psychotherapy research.

IDENTIFICATION OF QUESTIONABLE EXCLUSION CRITERIA IN MENTAL DISORDER CLINICAL TRIALS USING A MEDICAL ENCYCLOPEDIA.

Inclusion criteria for acute uncomplicated cystitis.

Choosing inclusion criteria that minimize the time and cost of clinical trials.

Randomized controlled clinical trials and meta-analyses.

What proportion of chronic obstructive pulmonary disease outpatients is eligible for inclusion in randomized clinical trials?

Randomized controlled trials: who fails run-in?