Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder

760 Pages·2013·5.83 MB·English

Comparative Effectiveness Review
Number 92
Psychological and
Pharmacological
Treatments for Adults With
Posttraumatic Stress
Disorder (PTSD)
Comparative Effectiveness Review
Number 92

Psychological and Pharmacological Treatments for
Adults With Posttraumatic Stress Disorder (PTSD)

Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
540 Gaither Road
Rockville, MD 20850
www.ahrq.gov

Contract No. 290-2007-10056-I

Prepared by:
RTI International–University of North Carolina Evidence-based Practice Center
Research Triangle Park, NC

Investigators:
Daniel E. Jonas, M.D., M.P.H.
Karen Cusack, Ph.D.
Catherine A. Forneris, Ph.D., A.B.B.P.
Tania M. Wilkins, M.S.
Jeffrey Sonis, M.D., M.P.H.
Jennifer Cook Middleton, Ph.D.
Cynthia Feltner, M.D., M.P.H.
Dane Meredith, M.P.H.
Jamie Cavanaugh, Pharm.D.
Kimberly A. Brownley, Ph.D.
Kristine Rae Olmsted, M.S.P.H.
Amy Greenblatt, B.A.
Amy Weil, M.D.
Bradley N. Gaynes, M.D., M.P.H.

AHRQ Publication No. 13-EHC011-EF
April 2013
This report is based on research conducted by the RTI International–University of North
Carolina Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare
Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10056-I). The findings
and conclusions in this document are those of the authors, who are responsible for its contents;
the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no
statement in this report should be construed as an official position of AHRQ or of the U.S.
Department of Health and Human Services.

The information in this report is intended to help health care decisionmakers—patients and
clinicians, health system leaders, and policymakers, among others—make well-informed
decisions and thereby improve the quality of health care services. This report is not intended to
be a substitute for the application of clinical judgment. Anyone who makes decisions concerning
the provision of clinical care should consider this report in the same way as any medical
reference and in conjunction with all other pertinent information, i.e., in the context of available
resources and circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for development of clinical practice
guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage
policies. AHRQ or U.S. Department of Health and Human Services endorsement of such
derivative products may not be stated or implied.

This document is in the public domain and may be used and reprinted without special
permission. Citation of the source is appreciated.

Persons using assistive technology may not be able to fully access information in this report. For
assistance contact [email protected].

None of the investigators have any affiliations or financial involvement that conflicts with the
material presented in this report.

Suggested citation: Jonas DE, Cusack K, Forneris CA, Wilkins TM, Sonis J, Middleton JC,
Feltner C, Meredith D, Cavanaugh J, Brownley KA, Olmsted KR, Greenblatt A, Weil A, Gaynes
BN. Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress
Disorder (PTSD). Comparative Effectiveness Review No. 92. (Prepared by the RTI
International–University of North Carolina Evidence-based Practice Center under Contract No.
290-2007-10056-I.) AHRQ Publication No. 13-EHC011-EF. Rockville, MD: Agency for
Healthcare Research and Quality; April 2013.
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
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Preface
The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based
Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and
private-sector organizations in their efforts to improve the quality of health care in the United
States. These reviews provide comprehensive, science-based information on common, costly
medical conditions, and new health care technologies and strategies.
Systematic reviews are the building blocks underlying evidence-based practice; they focus
attention on the strength and limits of evidence from research studies about the effectiveness and
safety of a clinical intervention. In the context of developing recommendations for practice,
systematic reviews can help clarify whether assertions about the value of the intervention are
based on strong evidence from clinical studies. For more information about AHRQ EPC
systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm.
AHRQ expects that these systematic reviews will be helpful to health plans, providers,
purchasers, government programs, and the health care system as a whole. Transparency and
stakeholder input are essential to the Effective Health Care Program. Please visit the Web site
(www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an
email list to learn about new program products and opportunities for input.
We welcome comments on this systematic review. They may be sent by mail to the Task
Order Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road,
Rockville, MD 20850, or by email to [email protected].

Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H.
Director Director, Center for Outcomes and Evidence
Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality

Stephanie Chang, M.D., M.P.H.
Director, EPC Program
Task Order Officer
Center for Outcomes and Evidence
Agency for Healthcare Research and Quality

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Acknowledgments
We gratefully acknowledge the support of our AHRQ Task Order Officer, Stephanie Chang,
M.D., M.P.H., and the support of our former AHRQ Task Order Officer, Sonia Tyutyulkova,
M.D., Ph.D. We extend our appreciation to our Key Informants and members of our Technical
Expert Panel (listed below), all of whom provided thoughtful advice and input during our
research process.
The investigators deeply appreciate the considerable support, commitment, and contributions
of the EPC staff at RTI International and the University of North Carolina at Chapel Hill. We
express our gratitude to the following individuals for their contributions to this project: Carol
Woodell, B.S.P.H., our Project Manager; Megan Van Noord, M.S.L.S., and Christiane Voisin,
our EPC Librarians; Kathleen Lohr, Ph.D, scientific editor; Jennifer Drolet, Carol Offen, and
Wally Campbell, editors; and Loraine Monroe, our EPC publications specialist.
Key Informants
In designing the study questions, the EPC consulted several Key Informants who represent
the end-users of research. The EPC sought the Key Informant input on the priority areas for
research and synthesis. Key Informants are not involved in the analysis of the evidence or the
writing of the report. Therefore, in the end, study questions, design, methodological approaches,
and/or conclusions do not necessarily represent the views of individual Key Informants.
Key Informants must disclose any financial conflicts of interest greater than $10,000 and any
other relevant business or professional conflicts of interest. Because of their role as end-users,
individuals with potential conflicts may be retained. The TOO and the EPC work to balance,
manage, or mitigate any conflicts of interest.
The list of Key Informants who participated in developing this report follows:

Christine Courtois, Ph.D. Laura Fochtmann, M.D.
Principal and Founder of Courtois & Medical Editor of the American Psychiatric
Associates, PC Association Practice Guidelines
Trauma Treatment, Life Transitions, and Professor of Psychiatry and Director of the
Wellness Services ECT Service
Washington, DC Stony Brook University Medical Center
Stony Brook, NY
Jonathan R. Davidson, M.D.
Professor Emeritus, Psychiatry-Psychiatry & Matthew J. Friedman, M.D., Ph.D.
Behavioral Sciences and Executive Director
Director of the Anxiety and Traumatic National Center for Posttraumatic Stress
Stress Program Disorder
Duke University Medical Center U.S. Department of Veterans Affairs
Durham, NC Professor of Psychiatry and of
Pharmacology and Toxicology
Dartmouth Medical School
Hanover, NH

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Daniel I. Galper, Ph.D. Rachel Kimerling, Ph.D.
Director of Research & Special Projects National Center for Posttraumatic Stress
American Psychological Association Disorder
Washington, DC VA Palo Alto Health Care System
Center for Health Care Evaluation
Palo Alto, CA
Technical Expert Panel
In designing the study questions and methodology at the outset of this report, the EPC
consulted several technical and content experts. Broad expertise and perspectives were sought.
Divergent and conflicted opinions are common and perceived as healthy scientific discourse that
results in a thoughtful, relevant systematic review. Therefore, in the end, study questions, design,
methodologic approaches, and/or conclusions do not necessarily represent the views of
individual technical and content experts.
Technical Experts must disclose any financial conflicts of interest greater than $10,000 and
any other relevant business or professional conflicts of interest. Because of their unique clinical
or content expertise, individuals with potential conflicts may be retained. The TOO and the EPC
work to balance, manage, or mitigate any potential conflicts of interest identified.
The list of Technical Experts who participated in developing this report follows:

Naomi Breslau, Ph.D. Melanie S. Harned, Ph.D.
Professor of Epidemiology University of Washington
Michigan State University Behavioral Research & Therapy Clinics
East Lansing, MI Seattle, WA

Jonathan R. Davidson, M.D. Dean G. Kilpatrick, Ph.D.
Professor Emeritus, Psychiatry-Psychiatry & Distinguished University Professor of
Behavioral Sciences and Clinical Psychology
Director of the Anxiety and Traumatic Director, National Crime Victims Research
Stress Program & Treatment Center
Duke University Medical Center Vice-Chair for Research and Research
Durham, NC Administration
Department of Psychiatry & Behavioral
Laura Fochtmann, M.D. Sciences
Medical Editor of the American Psychiatric Medical University of South Carolina
Association Practice Guidelines Charleston, SC
Professor of Psychiatry and Director of the
ECT Service Jane Liebschutz, M.D., M.P.H.
Stony Brook University Medical Center Associate Professor
Stony Brook, NY Boston University School of Medicine
Department of Medicine
Daniel I. Galper, Ph.D. Boston, MA
Director of Research & Special Projects
American Psychological Association
Washington, DC

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Peer Reviewers
Prior to publication of the final evidence report, EPCs sought input from independent Peer
Reviewers without financial conflicts of interest. However, the conclusions and synthesis of the
scientific literature presented in this report does not necessarily represent the views of individual
reviewers.
Peer Reviewers must disclose any financial conflicts of interest greater than $10,000 and any
other relevant business or professional conflicts of interest. Because of their unique clinical or
content expertise, individuals with potential nonfinancial conflicts may be retained. The TOO
and the EPC work to balance, manage, or mitigate any potential nonfinancial conflicts of interest
identified.
The list of Peer Reviewers follows:

Laura Fochtmann, M.D. Jane Liebschutz, M.D., M.P.H.
Medical Editor of the American Psychiatric Associate Professor
Association Practice Guidelines Boston University School of Medicine
Professor of Psychiatry and Director of the Department of Medicine
ECT Service Boston, MA
Stony Brook University Medical Center
Stony Brook, NY Paula Schnurr, Ph.D.
Deputy Executive Director, VA National
Matthew J. Friedman, M.D., Ph.D. Center for PTSD
Executive Director, National Center for Research Professor of Psychiatry
Posttraumatic Stress Disorder Dartmouth Medical School
U.S. Department of Veterans Affairs Hanover, NH
Professor of Psychiatry and of
Pharmacology and Toxicology
Dartmouth Medical School
Hanover, NH

Helena Kraemer, Ph.D.
Professor Emerita of Biostatistics in
Psychiatry
Academy Council, Psychiatry & Behavioral
Science
School of Medicine, Stanford University
Stanford, CA

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Psychological and Pharmacological Treatments for
Adults With Posttraumatic Stress Disorder (PTSD)
Structured Abstract
Objectives. To assess efficacy, comparative effectiveness, and harms of psychological and
pharmacological treatments for adults with posttraumatic stress disorder (PTSD).

Data sources. MEDLINE®, Cochrane Library, PILOTS, International Pharmaceutical Abstracts,
CINAHL®, PsycINFO®, Web of Science, Embase, U.S. Food and Drug Administration Web site,
and reference lists of published literature (January 1980–May 2012).

Review methods. Two investigators independently selected, extracted data from, and rated risk
of bias of relevant trials. We conducted quantitative analyses using random-effects models to
estimate pooled effects. To estimate medications’ comparative effectiveness, we conducted a
network meta-analysis using Bayesian methods. We graded strength of evidence (SOE) based on
established guidance.

Results. We included 92 trials of patients, generally with severe PTSD and mean age of 30s to
40s. High SOE supports efficacy of exposure therapy for improving PTSD symptoms (Cohen’s d
-1.27; 95% confidence interval, -1.54 to -1.00); number needed to treat (NNT) to achieve loss of
diagnosis was 2 (moderate SOE). Evidence also supports efficacy of cognitive processing
therapy (CPT), cognitive therapy (CT), cognitive behavioral therapy (CBT)-mixed therapies, eye
movement desensitization and reprocessing (EMDR), and narrative exposure therapy for
improving PTSD symptoms and/or achieving loss of diagnosis (moderate SOE). Effect sizes for
reducing PTSD symptoms were large (e.g., 28.9- to 32.2-point reduction in Clinician-
Administered PTSD Scale [CAPS]; Cohen’s d ~ -1.0 or more compared with controls); NNTs
were ≤ 4 to achieve loss of diagnosis for CPT, CT, CBT-mixed, and EMDR.

Evidence supports the efficacy of fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine
for improving PTSD symptoms (moderate SOE); effect sizes were small or medium (e.g., 4.9- to
15.5-point reduction in CAPS compared with placebo). Evidence for paroxetine and venlafaxine
also supports their efficacy for inducing remission (NNTs ~8; moderate SOE). Evidence
supports paroxetine’s efficacy for improving depression symptoms and functional impairment
(moderate SOE) and venlafaxine’s efficacy for improving depression symptoms, quality of life,
and functional impairment (moderate SOE). Risperidone may help PTSD symptoms (low SOE).
Network meta-analysis of 28 trials (4,817 subjects) found paroxetine and topiramate to be more
effective than most medications for reducing PTSD symptoms, but analysis was based largely on
indirect evidence and limited to one outcome measure (low SOE).

We found insufficient head-to-head evidence comparing efficacious treatments; insufficient
evidence to verify whether any treatment approaches were more effective for victims of
particular trauma types or to determine comparative risks of adverse effects.

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Conclusions. Several psychological and pharmacological treatments have at least moderate SOE
supporting their efficacy: exposure, CPT, CT, CBT-mixed therapies, EMDR, narrative exposure
therapy, fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine.

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Contents
Executive Summary .................................................................................................................ES-1
Introduction ....................................................................................................................................1
Background ............................................................................................................................... 1
Epidemiology of PTSD ........................................................................................................1
Existing Guidance ..................................................................................................................... 6
Scope and Key Questions ....................................................................................................6
Analytic Framework ............................................................................................................7
Methods ...........................................................................................................................................9
Topic Refinement and Review Protocol ................................................................................... 9
Literature Search Strategy......................................................................................................... 9
Search Strategy ....................................................................................................................9
Inclusion and Exclusion Criteria ........................................................................................10
Study Selection ..................................................................................................................13
Data Extraction ..................................................................................................................13
Risk of Bias Assessment of Individual Studies ...................................................................... 14
Data Synthesis ......................................................................................................................... 15
Strength of the Body of Evidence ........................................................................................... 17
Applicability............................................................................................................................ 17
Peer Review and Public Commentary .............................................................................. 18
Results ...........................................................................................................................................19
Introduction ............................................................................................................................. 19
Results of Literature Searches........................................................................................... 19
Key Question 1: Comparative Effectiveness of Different Psychological Treatments
for Posttraumatic Stress Disorder ..................................................................................... 21
Key Points: Overall—Efficacy ..........................................................................................22
Key Points: Overall—Comparative Effectiveness.............................................................24
Detailed Synthesis: CBT—Cognitive Therapy ..................................................................27
Detailed Synthesis: CBT—Coping Skills ..........................................................................36
Detailed Synthesis: CBT—Exposure .................................................................................41
Detailed Synthesis: CBT—Mixed Interventions ...............................................................55
Detailed Synthesis: Eye Movement Desensitization and Reprocessing (EMDR) .............65
Detailed Synthesis: Other Psychological Interventions .....................................................71
Key Question 2. Comparative Effectiveness of Different Pharmacological
Treatments for Adults With PTSD.................................................................................... 82
Key Points: Overall—Efficacy ..........................................................................................83
Key Points: Overall—Comparative Effectiveness.............................................................84
Detailed Synthesis: Placebo-Controlled Trials of Alpha-Blockers....................................86
Detailed Synthesis: Placebo-Controlled Trials of Anticonvulsants/Mood Stabilizers ......87
Detailed Synthesis: Placebo-Controlled Trials of Atypical Antipsychotics ......................91
Detailed Synthesis: Placebo-Controlled Trials of Benzodiazepines ..................................93
Detailed Synthesis: Selective Serotonin Reuptake Inhibitors (SSRIs) ..............................94
Detailed Synthesis: Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) ..........101
Detailed Synthesis: Placebo-Controlled Trials of Tricyclic Antidepressants ..................103
Detailed Synthesis: Placebo-Controlled Trials of Other Second-Generation
Antidepressants ..........................................................................................................104
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