Treatment of Posttraumatic Stress Disorder: An Assessment of the Evidence (2008)

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2 Methods T his chapter describes the methods the committee used to search and organize the literature, assess the quality of studies, and reach conclusions about the strength of the evidence regarding efficacy of various treatment modalities for posttraumatic stress disorder (PTSD). THE LITERATURE SEARCH An extensive search of the published scientific literature of PTSD treatment was conducted and over 2,000 potentially relevant references were retrieved. The following categories were of primary interest to the committee: 1. Meta-analyses and reviews of effectiveness of drug therapies and psychotherapies in all populations with PTSD 2. Clinical trials and epidemiological studies of drug therapies and psychotherapies for veterans with PTSD and/or anxiety disorders 3. Studies other than meta-analyses, reviews, clinical trials, or epide- miological studies that discuss drug therapies and psychotherapies for veterans with PTSD 4. Studies of treatment outcomes, progression, prognosis, or recovery for veterans with PTSD National Academies committees are required to make publicly available all material ­reviewed in the course of their deliberation and used in preparing reports and making recom­mendations. For this reason, the committee did not use any unpublished material in its review. 39 

40 TREATMENT OF POSTTRAUMATIC STRESS DISORDER The committee’s database searches used the National Library of Medicine’s Medical Subject Headings (MeSH) keyword nomenclature developed for MEDLINE. Searches included terms for drug interventions, psycho­therapy interventions, and study design, and were limited to ­studies published in English, after 1980, and conducted in adult populations (≥18 years old). The committee also reviewed selected reference lists of relevant review articles, meta-analyses, and books. The committee did not undertake a systematic search for unpublished data. A more detailed explana­tion of this search can be found in Appendix B. Databases con- sulted include: • MEDLINE, • EMBASE (Excerpta Medica), • PsycINFO, • Cochrane Database of Systematic Reviews, • Cochrane Controlled Trials Register, • National Technical Information Service (NTIS), • Social service abstracts, and • Database of Abstracts of Reviews of Effectiveness (DARE). The searches identified a total of 2,771 sources. All citations were imported into an electronic database (EndNote). Table 2-1 outlines the sources of the citations. The committee developed criteria for inclusion and exclusion based on the patient populations and outcome measures (see Box 2-1 for specific cri- teria). Once the nonrelevant studies were eliminated—including those that were not on treatment (many were on assessment and diagnosis of PTSD, biologic markers for PTSD, or were not in a PTSD population)—each abstract was reviewed for relevance, and the full text was retrieved for all potentially relevant abstracts for further review, with the guidance of all committee members. Decisions to include and exclude studies were made by the committee. This review focused on adult patients (ages 18 years and older) with PTSD diagnosed by the study investigators according to Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. That is why the committee’s search included only studies published beginning in 1980, when the first DSM definition was published. Studies with patients of mixed diagnoses (e.g., some with diagnosed PTSD, others subsyndromal) only were included if results were reported separately for the relevant ­subgroups. In1980 the Diagnostic and Statistical Manual of Mental Disorders (DSM) first recognized PTSD as a disorder and provided a definition and symptoms list. 

METHODS 41 TABLE 2-1  Number of Citations, by Source Source Number of Citations MEDLINE 1554 EMBASE 578 PsycINFO 334 Cochrane Database of Systematic Reviews 11 Cochrane Controlled Trials Register 28 NTIS 151 Social service abstracts 97 DARE 18 Total 2771 BOX 2-1 Inclusion Criteria for Review • Randomized controlled trial (RCT; randomized comparative trials were only used if RCTs for a given modality demonstrated efficacy ) • PTSD diagnosis based on DSM criteria • Published between 1980 and June 2007 • Adults ages 18 and older • PTSD outcome measure included (primary or secondary measure) • English language This review also included only primary research and no reanalyses of prior research. The committee was charged to “report on the highest levels of evidence available.” Although the number of studies for some treatment modalities was small, in most cases randomized controlled trials were available for review. (For clarity, it should be noted that in the psychotherapy studies, the control was not placebo, but wait list, usual care, or a type of active control.) Therefore, per part II.B of the Statement of Task, only level-I stud- ies (RCTs) were included in the committee’s review. The committee recog- nizes that study designs other than RCTs can be informative for questions of effective­ness and other outcomes, but did not believe that non-RCTs would inform the core question of treatment efficacy. The committee judged When there was more than one primary study based on the same data, the study with the most complete data set was used. 

42 TREATMENT OF POSTTRAUMATIC STRESS DISORDER that, in general, questions of treatment efficacy are best addressed in high q ­ uality RCTs because the variability of treatments, outcome measures, course of the disorder, and patient and provider preferences make studies of other designs unreliable in making causal inferences. The committee fur- ther reasoned that the specific characteristics of PTSD (multiple symptom clusters, occurring in various combinations in patients), its measurement (multiple outcome measures, some with several scales), and its treatment (a wide range of pharmacotherapy and psychotherapy options) were of such heterogeneity and fragmentation that observational studies were unlikely to provide sufficiently valid and reproducible evidence to be considered in addition to the RCTs. Data Abstraction The committee developed an evidence table template and database for abstracting data from the included studies. Once the evidence table data were abstracted by staff, committee members worked in pairs to check the tables for completeness and to assess the quality of the study as well as its contribution to the evidence regarding efficacy of the treatment. The following information was extracted from all included studies if avail- able: geographical location; setting; study design; interventions (including dose, duration, dose protocol, concurrent interventions, and clinician); population characteristics (including age, sex, race/ethnicity, education, trauma type and duration, concurrent medications, psychotherapies, and co­morbidities); study inclusion and exclusion criteria; number screened, number enrolled, and completion rates; funding source; and results for PTSD outcomes as well as outcomes on depression, anxiety, and quality-of- life measures. Additionally, information was abstracted on whether or not adverse events were reported, if meeting diagnostic criteria after treatment was reported, and if the study included veterans. REACHING CONCLUSIONS REGARDING THE EFFICACY OF TREATMENT MODALITIES The committee was charged with making conclusions about the strength of the available evidence for treatment modalities according to the following framework: 1. Evidence is sufficient to conclude the efficacy of X in the treatment of PTSD. 2. Evidence is suggestive but not sufficient to conclude the efficacy of X in the treatment of PTSD. 

METHODS 43 3. Evidence is inadequate to determine the efficacy of X in the treat- ment of PTSD. 4. Evidence is suggestive that X treatment is ineffective in treating PTSD. 5. Evidence is suggestive that X treatment is harmful in the treatment of PTSD. Conclusions 4 and 5 (suggesting and concluding ineffectiveness/harm) are mirror images of conclusions 2 and 1 (suggesting and concluding ef- ficacy). The data extraction and review processes addressed the question of whether there was a body of evidence regarding the effect of a treat- ment modality in either direction—efficacy or inefficacy. Thus the five conclusions above collapsed into making only three conclusions regarding a treatment modality: evidence sufficient to conclude its effect (positive or negative); evidence suggestive but not sufficient to conclude its effect (posi- tive or negative); and evidence inadequate to conclude its effect (positive or negative). The committee viewed the conclusion of inadequate evidence as a neutral position with respect to efficacy—neither concluding that the modality was effective or ineffective. Assessing the Literature to Reach Conclusions The committee made an assessment of both the strength of the indi- vidual studies comprising the body of evidence, and the overall sufficiency of that body of evidence for judging treatment efficacy. The assessment of strength of individual studies was based on the degree to which the studies adhered to current scientific standards in design and analysis (see Criteria to Assess a Study’s Quality in Box 2-2) as well as the estimated magnitude of effect and precision of that estimate. In making its conclusions regarding efficacy, the committee found most informative those studies that failed the fewest criteria and that did not have major limitations. The committee further assessed the overall body of evidence for each treatment modality with attention to the volume of studies meeting quality criteria, the consistency of the direction of the effect among studies (e.g., positive, negative, or mixed), the size of the studies (small: <30 participants per treatment condition; moderate: 30–99 per arm; large: >99 per arm), the statistical significance of the findings, the magnitude of the e ­ ffect (including its clinical significance), and the length of follow-up. A high-quality study that was small might produce weak evidence b ­ ecause the small size leads to an uncertain estimate of effect, whereas a low-quality large study might also produce weak evidence because the low ­ quality leads to biased estimates of effect. The assessment of overall s ­ ufficiency of evidence for judging treatment efficacy depended on the 

44 TREATMENT OF POSTTRAUMATIC STRESS DISORDER BOX 2-2 Criteria to Assess a Study’s Quality • Assembly of comparable groups (randomized,** similar distributions of known confounders). • Maintenance of comparable groups (i.e., minimal attrition, crossovers, or con- tamination, good adherence). Use of intention to treat (ITT) analysis. • Measurements equal, valid, and reliable (validated PTSD outcome measure, double masking in pharmacotherapy studies** and assessor blinding or at least assessor independence** in psychotherapy studies). • Loss to follow-up causing missing outcome data: — Differential loss to follow-up no greater than 15% absolute difference be- tween groups.** — If approximately equal loss to follow-up in each arm, study quality is af- fected by the analytic methods used to handle missing data: o Up to 10% missing outcome data acceptable without formal missing data methods employed (i.e., may use completer analysis or last ob- servation carried forward [LOCF]). o Between 10% and 40% missing outcome data acceptable depending on validity of missing data analytic method employed (e.g., for lower proportions, single imputation, for higher proportions, likelihood-based methods, multiple imputation, sensitivity analysis). o Use of LOCF decreases study quality as the percentage dropout in- creases, severely if dropout exceeds 30%. Completer analysis is not acceptable.** o No more than 40% loss to follow-up in any arm.** **Indicates a criterion that if absent (or if the authors do not disclose) is a major limitation that limited the study’s usefulness to the committee in reaching its conclusion regarding efficacy.  strength of the individual studies, the consistency of the effects among stud- ies, and the degree to which the interventions, populations, and outcome measures used in those studies were deemed comparable. This overall suf- ficiency of the evidence for judging treatment efficacy was classified into the three categories (reflecting, as described above, the collapsed five conclu- sions listed in the committee’s charge): Sufficient to conclude the presence of a treatment effect, Suggestive but not sufficient, and Inadequate (see Box 2-3). 

METHODS 45 BOX 2-3 Assessments Leading to Conclusions of Efficacy “Evidence is sufficient . . .” • High quality of the body of evidence (i.e., more than one study) indicating a clinically meaningful treatment effect • High confidence in both the presence and magnitude of an effect • Future research is unlikely to change confidence in the estimate of effect “Evidence is suggestive but not sufficient . . .” • Moderate quality of the body of evidence, with the best studies all pointing in the same clinical direction • Moderate confidence in the presence of an effect, but not confident in the magnitude of the effect • Further research is likely to have an important impact on confidence in the estimate of the effect and may change the estimate • Moderate confidence that the effect will hold up in future studies of high quality “Evidence is inadequate . . .” • Low quality of the body of evidence (i.e., evidence comes from seriously flawed studies) • Not confident in the presence of an effect. Any estimate of effect is uncertain • Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate • Uncertainty whether future high-quality studies will show an effect Committee members found certain heuristics useful in thinking about the meaning of those categories (Box 2-3). One approach was to distin- guish between the confidence in the presence of a treatment effect and the magnitude of that effect. A body of evidence that produced high confidence in both the presence and size of the effect would be “sufficient”; moderate confidence in the presence of an effect but substantial uncertainty about the size of the effect (e.g., whether it was clinically meaningful) would be “suggestive”; and uncertainty about both the effect and its size would be “inadequate.” Another heuristic was to assess the robustness of the current evidence by imagining the impact of a high-quality moderate-size future study: if it were unlikely to impact conclusions about the presence or size of an effect, current evidence would be deemed “sufficient”; if it could meaningfully shift the strength of evidence, the current evidence pointing to an effect would be “suggestive”; and if it would effectively 

46 TREATMENT OF POSTTRAUMATIC STRESS DISORDER s ­ ubstitute for the current evidence, then the current evidence would be judged “inadequate.” Although all of these determinations were based on recognized prin- ciples and guidelines for evaluating evidence, there is no established algo- rithmic approach to these classifications and the committee did not use one. Instead, it attempted to be as transparent as possible in describing the foundations of its judgments, and these are reflected both in the evidence tables and in the “Synthesis” paragraphs immediately preceding statement of the conclusion for each treatment modality presented in Chapters 3 and 4. The evidence tables include population descriptors, sample size by arm and total, handling of missing data and dropout rates, information about blinding, PTSD outcome measure change data, loss of PTSD diagnosis data, and finally, a listing of a study’s principal limitations. SUMMARY OF THE LITERATURE REVIEWED IN MAKING CONCLUSIONS The final set of studies reviewed by the committee consisted of 89 total, with 37 studies of pharmacotherapies and 52 studies of psychotherapies. All studies were randomized controlled trials. Studies ranged in sample size from fewer than 20 to more than 500 and were conducted with a variety of patient populations: male, female, and mixed populations; various traumas (combat- and noncombat-related); more recent onset of the disorder and chronic PTSD; and so on. Studies reviewed also employed a range of PTSD outcome measures, from frequently used, validated measures such as the Clinician Assessment PTSD Scale (CAPS) and the Impact of Events Scale (IES), to more idiosyncratic measures sometimes developed for a specific study. The studies reviewed by the committee included a large number of outcome measures; a summary table of the measures most often encoun- tered in the literature is provided in Appendix C. SUMMARY OF EXISTING SYSTEMATIC REVIEWS AND META-ANALYSES In addition to its review of individual research studies, the commit- tee examined a number of systematic and qualitative reviews and meta- a ­ nalyses. Some reviewed both psychotherapies and pharmacotherapies, PTSD outcome measure change data were obtained either directly from the study, when provided, or by subtracting data reported at treatment completion (not follow-up data) from baseline data (before treatment began). Average baseline score when reported or when base- line scores for all arms are nearly the same; otherwise, baseline scores listed individually in order of arm. 

METHODS 47 others focused on a category or class of treatment (e.g., selective serotonin reuptake inhibitors [SSRIs]) and yet others on a specific treatment modality (e.g., sertraline). None of the reviews exactly coincided with the committee’s charge or purpose, and none of the reviews used the same inclusion and e ­ xclusion criteria, criteria to assess quality, and methods to reach conclu- sions as did the committee. Many of the reviews did not publish exactly how the literature was identified, assessed, and summarized. Thus the com- mittee found it interesting to see how others have conceptualized the field and conducted reviews, and used the reviews to make sure that the com- mittee’s literature search was exhaustive and comprehensive. However, the committee could not use the existing systematic reviews and meta-analyses to directly inform its assessments of the efficacy of specific interventions. The summaries below are presented as general background. The descriptive reviews included Foa and Meadows (1997), Hembree and Foa (2003), and others. The meta-analyses included two issued by the Cochrane Collaboration (Bisson and Andrew, 2006; Stein et al., 2006). Brief summaries are provided below. Hembree and Foa conducted a qualitative review of pharmaco­therapies and psychotherapies used with crime victims (Hembree and Foa, 2003). They considered a variety of designs, including open-label studies. Findings included significant reduction in symptoms with SSRI treatment, ­monoamine oxidase inhibitors (MAOIs) were found moderately effective, and tricyclic antidepressants (TCAs) were mildly effective for patients with chronic PTSD. The authors also found equivalent outcomes among exposure; cogni- tive therapy, stress inoculation training (SIT), and a combination of the two; and eye movement desensitization and reprocessing (EMDR), though they noted that dismantling studies suggest eye movements are not integral. The SSRI studies showed them to be the first-line medication because of their relative safety profile and their efficacy in improving comorbid conditions (depression, panic, obsessive-compulsive disorder). Van Etten and Taylor (1998) reviewed both pharmacotherapy and psychotherapy for PTSD. Inclusion criteria were patients diagnosed based on DSM criteria, studies where N≥5, and outcome measures were reliable and valid (including nonrandomized, uncontrolled) (van Etten and Taylor, 1998). The authors included 38 studies and 1,029 completers. Psycho- therapy studies had lower dropout rates than pharmacotherapy studies (14 percent versus 32 percent), and psychotherapies were more effective in reducing symptoms. Both pharmacotherapy and psychotherapy were more effective versus controls. The greatest effect size in pharmacotherapy studies The committee considered including effect size or weighted means differential data for each meta-analysis summarized, but it concluded that relaying such results alone in the absence of other data is not particularly useful for the interested reader. 

48 TREATMENT OF POSTTRAUMATIC STRESS DISORDER was found in SSRI studies and the one carbamazepine study. The greatest effect size in psychotherapy studies was in behavior therapy and EMDR, but EMDR used significantly fewer sessions and took less time. Foa and Meadows (1997) reviewed psychotherapy studies. They found the evidence for efficacy of exposure and SIT most robust, the evidence on cognitive processing therapy promising, and the evidence on EMDR mixed and “inundated with methodological flaws.” Their assessment of studies of hypnotherapy and psychodynamic was that the research in this area lacked rigor (studies were mostly case reports) or had methodological prob- lems. Furthermore, they found that combined therapies, such as SIT with prolonged exposure, did not appear to be superior to their components, and without studies dismantling them it was not possible to discern which components were most active. The committee reviewed the Cochrane systematic review of psycho- therapies (Bisson and Andrew, 2006) that examined 26 RCTs of interven- tions they divided into four categories: trauma-focused cognitive-behavioral therapy (CBT), stress management (or nontrauma-focused CBT, roughly equivalent to the committee’s category of coping skills training therapies), other therapies (supportive therapy, nondirective counseling, psycho­dynamic therapy, and hypnotherapy), and group CBT. (The review did not include EMDR; the authors expected to add and reissue the review early in 2007, but no update was available at the time of this writing.) The meta-analysis found both trauma-focused CBT and stress management significantly better than wait list or usual care. There was no significant difference between trauma-focused CBT and stress management, and both were better than other therapies, and those, in turn, were not significantly different from wait list or usual care. Group trauma-focused CBT was also found to be significantly better than wait list or usual care. Bradley et al. (2005) conducted a meta-analysis of psychotherapy RCTs with more than 10 subjects published between 1980 and 2003. The treat- ments reviewed include exposure, CBT, exposure plus CBT, and EMDR. The meta-analysis included 26 studies and 1,535 patients. The authors found no significant difference in comparing treatment against wait list or standard care. Harvey et al. (2003) conducted a descriptive review of the CBT litera- ture and organized their findings by type of trauma. They found strong support for CBT interventions, but identified methodologic weaknesses in many of the studies they reviewed. Harvey and colleagues also briefly described some of the evidence and some key issues (e.g., methodologic problems) in EMDR research. Sherman (1998) evaluated 17 controlled studies of psychotherapy, 11 of which were in populations with combat-related trauma. This meta-­analysis 

METHODS 49 found support for exposure therapy both in populations with combat and noncombat-related trauma. Shepherd et al. (2000) reviewed 16 RCTs comparing EMDR to another psychotherapy, to EMDR variants, or to delayed EMDR. The authors found that the studies varied in methodologic quality, and were generally small, most lacked assessor blinding, and had high rates of loss to follow- up. Fifteen of 16 studies showed positive treatment effects for EMDR. Maxfield and Hyer (2002) reviewed the EMDR literature. Their ­analysis included calculated effect sizes and evaluating methodology using Foa and Meadows’ (1997) gold standards (the authors assigned scores of 0, 0.5, or 1 on a scale of seven items). Their review included 12 RCTs remaining, 9 of which were above 5.5 mean on the quality evaluation, and they all found EMDR effective. Davidson and Parker (2001) reviewed 34 studies of EMDR and con- ducted a meta-analysis. They found great variation in methodologic quality, and found evidence of an effect in pre-post comparisons, and when EMDR was compared to psychotherapeutic approaches that excluded exposure. The Cochrane systematic review of pharmacotherapies for PTSD (Stein et al., 2006) included 35 short (14 weeks or less) randomized controlled trials, with a total of 4,597 participants. The reviewers found that a signifi- cantly greater proportion of patients responded to treatment compared to placebo (59.1 percent versus 38.5 percent), with the largest trials showing SSRI efficacy, including long-term efficacy. However, the authors noted, The current evidence base of RCTs is unable to demonstrate superior e ­ fficacy or acceptability for any particular medication class. Although some have suggested that the SSRIs are more effective than older anti­ depressants (Dow and Kline, 1997; Penava, 1996), class membership did not contribute significantly to the variation observed in symptom severity outcomes between trials, while the confidence intervals for the summary statistic of responder status on the seven SSRI trials overlapped with that of the MAOI and TCA trials. Comer and Figgitt (2000) reviewed the sertraline literature. They s ­ elected only large, well-controlled studies with appropriate statistical methodology. They identified five multicenter, double-blind RCTs with a total of 4,075 participants. The authors found significant effect in two of three civilian studies and in one of two veteran studies. Mooney et al. (2004) conducted a review of sertraline RCTs, open-label and uncontrolled studies, case series, and case reports. Twelve studies with a total of 1,159 subjects were included. Only 5 of the 12 studies were RCTs, and only these were included in the meta-analysis, which supported the use of sertraline (Mooney et al., 2004). 

50 TREATMENT OF POSTTRAUMATIC STRESS DISORDER In addition to the peer-reviewed literature, Effective Treatments for PTSD (Foa et al., 2000), the Practice Guidelines from the International ­ ociety for Traumatic Stress Studies, includes several descriptive reviews S (most were systematic) of the PTSD treatment literature: pharmacotherapy, CBT, EMDR, group therapy, psychodynamic therapy, and hypnosis. Sum- maries of these are provided below. First, Rothbaum et al. (2000) reviewed “empirical studies” of CBT, focusing on eight identified techniques including exposure and cognitive therapy, and several combined approaches. The authors used Foa and Meadows’ gold standard ratings and the Agency for Health Care Policy and Research (AHCPR) A–F ratings to review approximately 40 controlled and uncontrolled studies. Rothbaum and colleagues found the evidence of effectiveness for exposure conclusive, and also found evidence of effective- ness for SIT and cognitive processing therapy. They found combined CBT approaches (such as exposure plus SIT) were neither better nor worse than their components. Friedman (2000), in Foa et al. (2000), conducted a review of RCTs, open trials, and case reports. Their review gave greater weight to RCTs and also used the AHCPR A–F rating. The studies reviewed ­ included a num- ber of RCTs on SSRIs, benzodiazepines (one study), TCAs, and MAOIs. There were no RCTs, only other types of studies for anti­psychotics, anti­ convulsants, antiadrenergics and serotonergics, nefazodone, and ­traxodone. The evidence was strongest for TCAs, MAOIs, and SSRIs, but they were weak or mixed for serotonergic, alpha-adrenergic drugs, anticonvulsants, benzodiazepines, and antipsychotics. Chemtob et al., also in Foa et al. (2000), reviewed seven published RCTs of EMDR that found EMDR more efficacious than controls (wait list, routine care, and active treatment), but recommended further research to address the limitations of existing research. The systematic review of group therapy literature by Foy et al. (in Foa et al., 2000) identified 20 studies, only two of which were randomized. Most studies reported positive treatment outcomes, but most studies were characterized by methodologic limitations. The review of psychodynamic therapy (Kudler et al., also in Foa et al., 2000) described a literature that does not fit the RCT-oriented paradigm. The bulk of psychodynamic re- search consists of rich and interesting case studies, but extremely few em- ploy randomization or controls. Similarly, the hypnosis literature reviewed by Cardena et al. consisted of only one controlled study, but the review noted that other clinical reports in the literature have shown that hypnosis may be useful as an adjunct to other PTSD therapy. Now the Agency for Healthcare Research and Quality (AHRQ). 

METHODS 51 EVALUATING THE EVIDENCE In the chapters that follow, the committee applies the methods and background knowledge described in the present chapter to assess the avail- able evidence on PTSD treatment modalities, first pharmacotherapy (Chap- ter 3) then psychotherapy (Chapter 4). The narrative for each modality describes the committee’s assessments of individual studies and summarizes the body of evidence. The chapters include abbreviated evidence tables with key information about studies that contributed to reaching conclusions about the evidence regarding the efficacy of each treatment modality. REFERENCES Bisson, J., and M. Andrew. 2006. Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews (3):CD003388. Bradley, R., J. Greene, E. Russ, L. Dutra, and D. Westen. 2005. A multidimensional meta- analysis of psychotherapy for PTSD. American Journal of Psychiatry 162(2):214-227. Comer, A., and D. Figgitt. 2000. Sertraline: A review of its therapeutic use in post-traumatic stress disorder. Adis International 14(5):391-407(317). Davidson, P. R., and K. C. Parker. 2001. Eye movement desensitization and reprocess- ing (EMDR): A meta-analysis. Journal of Consulting and Clinical Psychology 69(2):305-316. Dow, B., and N. Kline. 1997. Antidepressant treatment of posttraumatic stress disorder and major depression in veterans. Annals of Clinical Psychiatry 9(1):1-5. Foa, E. B., and E. A. Meadows. 1997. Psychosocial treatments for posttraumatic stress d ­ isorder: A critical review. Annual Review of Psychology 48:449-480. Foa, E., T. Keane, and M. Friedman. 2000. Effective treatments for PTSD: Practice guidelines from the International Society for Traumatic Stress Studies. New York: The Guilford Press. Friedman, M. 2000. Pharmacotherapy. In Effective treatments for PTSD: Practice guidelines from the International Society for Traumatic Stress Studies. Edited by E. Foa, T. Keane, and M. Friedman. New York: The Guilford Press. Pp. 320-325. Harvey, A. G., R. A. Bryant, and N. Tarrier. 2003. Cognitive behaviour therapy for post­ traumatic stress disorder. Clinical Psychology Review 23(3):501-522. Hembree, E. A., and E. B. Foa. 2003. Interventions for trauma-related emotional disturbances in adult victims of crime. Journal of Traumatic Stress 16(2):187-199. Maxfield, L., and L. Hyer. 2002. The relationship between efficacy and methodology in studies investigating EMDR treatment of PTSD. Journal of Clinical Psychology 58(1):23-41. Mooney, P., J. Oakley, M. Ferriter, and T. R. 2004. Sertraline as a treatment for PTSD: A system- atic review and meta-analysis. Irish Journal of Psychological Medicine 21(3):100-103. Rothbaum, B. O., E. A. Meadows, P. Resick, and D. W. Fog. 2000. Cognitive–behavioral therapy. In Effective treatments for PTSD: Practice guidelines from the International Society for Traumatic Stress Studies. Edited by E. Foa, T. Keane, and M. Friedman. New York: The Guilford Press. Pp. 60-83. Shepherd J., K. Stein, and R. Milne. 2000. Eye movement desensitization and reprocessing in the treatment of post-traumatic stress disorder: A review of an emerging therapy. Psycho­ logical Medicine 30(4):863-871. Sherman, J. J. 1998. Effects of psychotherapeutic treatments for PTSD: A meta-analysis of controlled clinical trials. Journal of Traumatic Stress 11(3):413-435. 

52 TREATMENT OF POSTTRAUMATIC STRESS DISORDER Stein, D. J., J. C. Ipser, and S. Seedat. 2006. Pharmacotherapy for post traumatic stress dis­ order (PTSD). Cochrane Database Systematic Reviews (4):CD002795. van Etten, M., and S. Taylor. 1998. Comparative efficacy of treatment for post-traumatic stress disorder: A meta-analysis. Clinical Psychology and Psychotherapy 5:126-144. 



KEY for Tables 3-1 through 3-11: Arm = treatment condition PL = placebo DO = dropout rate PTSD outcome measures—refer to list of ITT = intent-to-treat analysis acronyms in Appendix E for full name LOCF = last observation carried forward of measure Misc = miscellaneous S&NS assault or abuse = sexual and N/A = not available nonsexual assault or abuse NR = not reported Tx = treatment NS = not significant 54