Background
Posttraumatic Stress Disorder
Posttraumatic stress disorder (PTSD) involves a group of symptoms experienced after exposure to a potentially traumatic event. Such symptoms may include re-experiencing the event; avoiding situations that trigger memories of the event; experiencing increased negative feelings and beliefs; experiencing feelings of hyperarousal such as irritability, agitation, anger, or being on alert; and experiencing various combinations of these indicators.90 The traumatic event (stressor) must involve either witnessing an actual or threatened death or serious injury or other threat to one’s physical integrity or witnessing an event that involves death, injury, or a threat to the physical integrity of another person. Alternatively, the event must involve learning about unexpected or violent death, serious harm, or threat of death or injury experienced by a family member or other close associate.90
Some traumatic events that are directly experienced include military combat, violent personal assault, being taken hostage, a terrorist attack, torture, natural or manmade disasters, and being diagnosed with a life-threatening illness.91 They can also comprise relational trauma such as sexual, physical, and emotional abuse and domestic violence. Not all people exposed to a potentially traumatic event, however, go on to develop posttraumatic stress symptoms and PTSD.
According to one meta-analysis of 35 longitudinal study samples, 28.8 percent (range: 3.1% to 87.5%) of adults exposed to one or more potentially traumatic events meet criteria for PTSD within 1 month of trauma exposure, and 17.0 percent continue to meet criteria for PTSD 12 months following exposure (range: 0.6% to 43.8%).92 PTSD is also highly comorbid with other psychiatric disorders; data from epidemiologic studies indicate that a vast majority of individuals with PTSD have a co-occurring disorder, most notably substance use disorders, mood disorders, anxiety disorders, and suicidality.93, 94
Individuals may vary in their response to various PTSD treatments. Moderators of treatment effectiveness include sociodemographic and health characteristics, such as racial and ethnic minorities; gender; types, severity, or chronicity of PTSD symptoms; and coexisting conditions. Employment factors such as current or past military or first responder service may also influence effectiveness of interventions. Finally, refugees and disaster victims may differ in their outcomes of PTSD therapies.
In the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5),91 PTSD criteria are analogous to, but not exactly the same as, the prior DSM-IV criteria.90 In DSM-5, PTSD has four symptom clusters: (1) intrusion (similar to the re-experiencing criterion in DSM-IV), (2) avoidance (without inclusion of numbing symptoms, as in DSM-IV), (3) negative alterations in cognition and mood, and (4) alterations in arousal and reactivity (similar to increased arousal in DSM-IV). Table 1 summarizes these criteria and major changes between the two DSM volumes. The severity of the symptoms of PTSD can be measured in clinical or research settings using a number of validated scales that typically result in a numeric score that roughly corresponds with the intensity, number, duration, subjective distress, or impact of symptoms on functioning.
Table 1
Diagnostic criteria for posttraumatic stress disorder.
Prevalence
The National Comorbidity Survey—Replication conducted between 2001 and 2003 estimated lifetime prevalence of PTSD based on DSM-IV criteria among all adults in the United States as 6.8 percent (9.7% in women and 3.4% in men) and current 12-month prevalence as 3.6 percent (5.2% in women and 1.8% in men).94 More recently collected data from the National Epidemiologic Survey on Alcohol and Related Conditions in 2012–2013 determined a lifetime prevalence of PTSD based on DSM-5 criteria among adults in the United States to be 6.1 percent (4.7% were determined to have past year [12-month] prevalence).93, 95 Military personnel have an elevated risk for exposure to trauma and, thus, an elevated risk for a PTSD diagnosis. Estimates from the National Vietnam Veterans Readjustment Survey found a DSM-IV lifetime PTSD prevalence estimate of 18.7 percent and a current PTSD prevalence estimate of 9.1 percent among Vietnam veterans.96 Surveys of military personnel returning from operations in Afghanistan and Iraq have yielded a wide range of PTSD estimates—for example, 12.6 percent of U.S. men who fought in Iraq and 6.2 percent of U.S. men who fought in Afghanistan. It is estimated that approximately 20 percent of female veterans of the conflicts in Iraq or Afghanistan suffer from PTSD in their lifetimes.97
Burden
The significant social, personal, and economic costs of PTSD exemplify the importance of this systematic review.98 People affected by PTSD have high rates of psychiatric comorbidity and have problems with functioning (e.g., family, work, social). They also tend to suffer adverse consequences over the life course such as difficulties with educational attainment, work earnings, marriage attainment, and child rearing.98 Almost one-half (42.6%) of adults with PTSD do not get mental health treatment.99 Among those who do, only 40.4 percent get minimally adequate treatment.99 Evidence-based guidelines define such therapy as receiving either appropriate pharmacotherapy for 2 or more months for the focal disorder plus more than four visits to any type of physician or eight or more psychotherapy visits with any health care or human services professional lasting an average of 30 minutes or more.99 Although studies have shown that about 92 percent of adults with lifetime PTSD eventually achieve remission, the median time to remission is 14 years.100
Treatment Strategies
Early diagnosis and appropriate treatment of people with PTSD are critical to reducing the duration and severity of symptoms, associated functional impairment, and associated costs.101 Treatment guidelines typically include guidance about both psychological and pharmacological types of treatments87, 88, 102–106 No clearly defined “preferred” approach to managing PTSD exists. However, many of the existing treatment guidelines support the use of trauma-focused psychological treatments for adults with PTSD, and most guidelines recognize at least some benefit of pharmacological treatments for PTSD. Some guidelines suggest trauma-focused psychological treatments over pharmacological treatments as a preferred first step and medications as an adjunct or a next-line treatment.104, 105
Practical considerations and patient preferences may guide treatment decisions. For example, the selection of an initial treatment plan may depend on whether the clinician can prescribe medications or provide psychotherapy. Finally, a patient’s coexisting physical or other mental health conditions (e.g., depression, anxiety, serious mental illness, eating disorders, chronic pain, gastrointestinal symptoms, or drug or alcohol use disorders) may influence the type of treatment selected.104, 105
Psychological Interventions
Specific psychological interventions have been studied for the treatment of PTSD. They include cognitive behavioral therapy (CBT) such as cognitive interventions, coping skills therapies, and exposure-based therapy; eye movement desensitization and reprocessing (EMDR); and other forms of individual and group therapies. Appendix A displays additional details about some commonly used psychological interventions to treat PTSD. The application of these treatments seeks to minimize the intrusion, avoidance, and hyperarousal symptoms of PTSD via some combination of learning and conditioning, working to change thought patterns and beliefs, re-experiencing and working through trauma-related memories and emotions, and teaching better methods of managing trauma-related stressors.
Pharmacological Interventions
Currently, the U.S. Food and Drug Administration has approved only paroxetine and sertraline for treating patients with PTSD. Other pharmacological agents that have been used as therapies for PTSD patients include the following: other selective serotonin reuptake inhibitors; serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants; other second-generation antidepressants; atypical antipsychotics; anticonvulsants and mood stabilizers; adrenergic agents; benzodiazepines; and other pharmacological agents such as naltrexone, cycloserine, and inositol.107, 108 Specific medications within these drug classes that have been studied or used in treating PTSD are listed in Table 2 in the Methods section below.
Outcomes
The primary outcome in PTSD treatment is symptom reduction. Authors often categorize symptom reduction into whether each respondent meets the remission criteria at posttreatment and followup assessments. Some studies also include loss of PTSD diagnosis as an outcome, defined as no longer meeting all PTSD criteria for number or type of requisite symptoms and/or functional impairment. Some commonly used instruments used to measure outcomes, which include both self-reported and clinician-administered assessments, are listed in Appendix B of this report. These instruments contain items assessing some or all of either DSM-IV or DSM-5 symptoms of PTSD; these cover domains such as exposure to a traumatic event, re-experiencing of symptoms, persistent arousal and numbing, and hyperarousal. Some instruments can be administered in as little as 5 minutes, whereas others take an hour or more to complete. These instruments are reliable and valid; some have acceptable psychometric properties across multiple subpopulations (e.g., active duty military personnel, veterans, trauma survivors, general population). Other outcomes often assessed in clinical practice include prevention or reduction of coexisting medical or psychiatric conditions, such as depressive symptoms, anxiety symptoms, or problematic substance use. Yet other end results of care can include improved quality of life, reduced functional limitations or disability, and ability to return to work or return to active duty.
Scope and Key Questions
Scope of the Review
Summary of Existing Clinical Practice Guidelines
Various guidelines and systematic reviews have yielded contradictory conclusions and recommendations regarding the comparative effectiveness and harms of psychological and pharmacological treatments for PTSD. In general, some guidelines identify psychological treatments over pharmacological treatments as the preferred first-line treatment, with medication to be used adjunctively or as a second option when psychotherapy does not adequately decrease symptoms and associated impairment. Other guidelines do not differentiate first-line versus other treatments. Although various evidence-based approaches to treatment exist, clinical uncertainty remains about which treatment to select for which patients. Furthermore, clinicians need to consider patient treatment preferences in treatment selection, given that selecting a treatment a patient does not prefer or value can affect treatment use, dropout rates, adherence to therapy, and therapeutic response. Numerous organizations have produced guidelines for treating PTSD: the American Psychiatric Association, the American Psychological Association, the U.S. Department of Veterans Affairs/U.S. Department of Defense, the National Institute for Health and Care Excellence in the United Kingdom, the National Health and Medical Research Council, the International Society for Traumatic Stress Studies, the American Academy of Child and Adolescent Psychiatry, Health and Medicine Division of the National Academies, and the World Health Organization.
The organizations and guideline developers used different methods, which may contribute to the variation in recommendations regarding the types of treatments and/or the order in which treatments should be used. Some guidelines are based on rigorous systematic reviews; others are based on expert consensus and less structured literature reviews. Differences in systematic review findings also may relate to the application of various rating systems to assess the strength of evidence (SOE) of the research findings. These methodological differences may lead, in part, to different syntheses of findings and overall conclusions, ultimately leading to variations in recommendations. Where one report found evidence to suggest efficacy of a particular treatment, another report deemed the underlying evidence inadequate to address efficacy and, therefore, was unable to make a recommendation.
Summary of Previous Systematic Review
The prior PTSD systematic review conducted for the Agency for Healthcare Quality and Research89 concluded that several psychological interventions (exposure therapy, cognitive processing therapy, cognitive therapy, CBT-mixed therapies, EMDR, and narrative exposure therapy) and pharmacological treatments (fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine) have at least moderate SOE in support of their efficacy. The review found sparse evidence of head-to-head comparisons between these interventions, however, limiting conclusions about comparative effectiveness.
Overall, the review found insufficient evidence of whether the efficacy or comparative effectiveness of different treatment approaches varied by patient characteristics or type of trauma experienced. Likewise, the review found limited evidence about adverse effects across different intervention types.
In addition to the need to update systematic reviews every few years109 when areas of clinical uncertainty remain, this updated review expands the scope of treatment types examined. Specifically, we include one psychological intervention not examined in the prior review, energy psychology (also known as emotional freedom techniques), and three atypical antipsychotics (namely, ziprasidone, aripiprazole, and quetiapine). We also assessed newer studies that might have used DSM-5 criteria to assess PTSD diagnosis to help shed light on the implications of the criteria change on the efficacy of treatments. No new studies, however, used DSM-5 criteria to assess PTSD. The change in criteria from DSM-IV to DSM-5 requires additional research; the field has yet to determine the impact of the changes. Synthesis of new and existing evidence addresses the uncertainties noted in the conclusions of our earlier systematic review about ways to improve the care of those with PTSD and to reduce the variation in existing treatment guidelines.
Key Questions
- KQ 4: What adverse events (AEs) are associated with treatments for adults diagnosed with PTSD?
Contextual Questions
Contextual Question (CQ) 1a. What are the components of effective psychological treatments (e.g., frequency or intensity of therapy and/or aspects of the therapeutic modality)?
CQ 1b. For psychological interventions that are effective in trial settings, what is the degree of fidelity when implemented in clinical practice settings?
Analytic Framework
Figure 1 depicts the analytic framework for the comparative effectiveness of psychological treatments and pharmacological treatments for adults with PTSD. We describe details of population, intervention, comparators, outcomes, timing, and setting in the Methods section below. Beginning with a population of adults diagnosed with PTSD, the figure illustrates the effect of psychological and pharmacological interventions on outcomes of PTSD. Those important outcomes include symptom reduction and remission, prevention or reduction of medical and psychiatric comorbid conditions, quality of life, disability or functional impairment, and ability to work or ability to return to either work or duty (KQ 1, KQ 2, and KQ 3). Patient characteristics and type of trauma are explored as potential moderators of these interventions in KQ 1a, KQ 2a, and KQ 3a. Finally, KQ 4 examines the AEs of these interventions.
Figure 1
Analytic framework for the comparative effectiveness of psychological treatments and pharmacological treatments for adults with PTSD. KQ = Key Question; PTSD = posttraumatic stress disorder.
Organization of This Report
We describe our methods next and then present our key findings in the Results chapter. In the Discussion chapter, we explore the implications of our findings and examine the limitations of the evidence base and this review, clarify gaps in the knowledge base, and offer recommendations for future research. References follow the appendixes.
The main report has several appendixes, as follows: A, intervention types; B, outcome measures and instruments; C, search strategies; D, excluded studies; E, risk of bias tables; F, evidence tables; G, high risk of bias study documentation; H, meta-analysis forest plots; I, strength of evidence; J, expert guidance and review.
Publication Details
Copyright
Publisher
Agency for Healthcare Research and Quality (US), Rockville (MD)
NLM Citation
Forman-Hoffman V, Middleton JC, Feltner C, et al. Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder: A Systematic Review Update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 May. (Comparative Effectiveness Review, No. 207.) Introduction.
