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Jonas DE, Cusack K, Forneris CA, et al. Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD) [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Apr. (Comparative Effectiveness Reviews, No. 92.)
This publication is provided for historical reference only and the information may be out of date.
Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD) [Internet].
Show detailsBackground
Posttraumatic stress disorder (PTSD) is a mental disorder that may develop following exposure to a traumatic event. According to the 4th edition of the “Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR,”1 the essential feature of PTSD is the development of characteristic symptoms following exposure to a traumatic stressor. PTSD is characterized by three core symptom clusters: (1) reexperiencing symptoms; (2) avoidance or numbing symptoms (or both); and (3) hyperarousal symptoms. The full DSM-IV TR criteria are listed in Table 1.
Table 1
Diagnostic criteria (DSM-IV-TR) for posttraumatic stress disorder.
Traumatic events that are directly experienced include the following: military combat, motor vehicle collisions, violent personal assault, being taken hostage, a terrorist attack, torture, natural or human-caused disasters, and, in some cases, being diagnosed with a life-threatening illness.1 According to a 2008 Institute of Medicine (IOM) report on the treatment of patients with PTSD, the condition “…develops in a significant minority (up to a third) of individuals who are exposed to extreme stressors, and symptoms of PTSD almost always emerge within days of the trauma.”2 PTSD is also frequently associated with other psychiatric disorders; data from epidemiologic studies have found that a high percentage of individuals with PTSD have another psychiatric disorder, most notably substance use disorders or major depressive disorder.3
Epidemiology of PTSD
Shortly after exposure to trauma, many people experience some of the symptoms of PTSD. In most people, those symptoms resolve spontaneously in the first several weeks after the trauma. However, in approximately 10 percent to 20 percent of those exposed to trauma, PTSD symptoms persist and are associated with impairment in social or occupational functioning.4 Although approximately 50 percent of those diagnosed with PTSD improve without treatment in one year, 10 percent to 20 percent develop a chronic unremitting course.5
The 2000 National Comorbidity Survey—Replication (NCS-R) estimated lifetime prevalence of PTSD among adults in the United States to be 6.8 percent (9.7% in women and 3.4% in men) and current (12-month) prevalence to be 3.6 percent (5.2% in women and 1.8% in men).6 The probability of development of PTSD is a function of both the probability of exposure to traumatic events and the risk of developing PTSD among those exposed to trauma.
Some demographic or occupational groups, such as military personnel, are at higher risk of PTSD because of higher rates of exposure to trauma. Estimates from the National Vietnam Veterans Readjustment Survey (NVVRS) found a lifetime PTSD prevalence estimate of 18.7 percent and a current PTSD prevalence estimate of 9.1 percent6 among Vietnam veterans. Surveys of military personnel returning from operations in Afghanistan and Iraq have yielded estimates ranging from 6.2 percent for U.S. service members who fought in Afghanistan to 12.6 percent for those who fought in Iraq.7 In addition to lives lost because of the increased risk of suicide,8 PTSD is associated with high medical costs and high social costs, because PTSD is a strong risk factor for poor work performance and associated job losses and familial discord. The economic cost of the PTSD and depression cases among Operation Enduring Freedom and Operation Iraqi Freedom veterans alone (including medical care, forgone productivity, and lives lost through suicide) is estimated at $4 billion to $6 billion over 2 years.9
Many people with PTSD do not seek treatment. Among those who do, many receive inadequate treatment or care that is not empirically based. Several PTSD outcome studies demonstrate the cost-effectiveness of early diagnosis and appropriate treatment, especially when compared with the cost of inadequate or ineffective treatment occurring before a correct diagnosis.10 In addition to consequences related to PTSD, people affected by these disorders have higher rates of psychiatric comorbidity, suffer decreased role functioning such as work impairment (on average, 3.6 days of work impairment per month), and experience many other adverse life-course consequences (e.g., reduced educational attainment, work earnings, marriage attainment, and child rearing).11
Treatment Strategies for PTSD
One primary outcome in PTSD treatment is symptom reduction, which includes both clinician-rated and self-reported measures. Appendix A describes each PTSD measure in detail. In addition to symptom reduction, other outcomes used in practice include remission (i.e., no longer having symptoms); loss of PTSD diagnosis; prevention or reduction of coexisting medical or psychiatric conditions (e.g., depressive symptoms, anxiety symptoms); improved quality of life; improved functioning; and ability to return to work or to active duty.
Treatments available for PTSD span a variety of psychological and pharmacological categories. These interventions are used both separately and in combination with one another, and both appear to be mainstays of treatment cited in treatment guidelines.12 Although no clearly defined “preferred” approach is available for managing patients with PTSD, each of these guidelines supports the use of trauma-focused psychological interventions (i.e., those that treat PTSD by directly addressing thoughts, feelings, or memories of the traumatic event) for adults with PTSD, and all, except the IOM report,2 recognize at least some benefit of pharmacological treatments for PTSD.12 Indeed, most guidelines identify trauma-focused psychological treatments over pharmacological treatments as a preferred first step and view medications as an adjunct or a next-line treatment.13–16 One guideline, from the International Society for Traumatic Stress Studies (ISTSS), recognizes that practical considerations, such as unavailability of trauma-focused psychological treatment or patient preferences, may guide treatment decisions.17
Psychological Interventions
Specific psychological interventions that have been studied for the treatment of patients with PTSD are described below. They include the following: brief eclectic psychotherapy; cognitive behavioral therapy (CBT), such as cognitive therapy, cognitive processing therapy, cognitive restructuring, coping skills therapies (including stress inoculation training), and exposure-based therapies; eye movement desensitization and reprocessing (EMDR); hypnosis and hypnotherapy; interpersonal therapy; and psychodynamic therapy. These therapies are designed to minimize the intrusion, avoidance, and hyperarousal symptoms of PTSD by either reexperiencing and working through trauma-related memories and emotions, targeting distorted cognitions, teaching better methods of managing trauma-related stressors, or a combination of these approaches.2 The therapies are delivered predominantly to individuals; some can also be conducted in a group setting.18,19 We will describe the individual form by default; if the treatment is provided in a group context, we will specifically indicate that.
Brief eclectic psychotherapy is a 16-session manualized treatment for PTSD that combines cognitive-behavioral and psychodynamic approaches.20,21 It consists of (1) psychoeducation, together with a partner or close friend; (2) imaginal exposure preceded by relaxation exercises, focused on catharsis of emotions of grief and helplessness; (3) writing tasks to express aggressive feelings and the use of mementos; (4) domain of meaning, focused on learning from the trauma; and (5) a farewell ritual, to end treatment. It was originally developed as a treatment for police officers, but it has also been used with other trauma samples.
CBT is a broad category of therapies based on principles of learning and conditioning and/or cognitive theory to treat disorders and includes components from both behavioral and cognitive therapy. In CBT, components such as exposure, cognitive restructuring, and various coping skills have been used either alone or in combination. Most forms of CBT consist of a minimum of 8 to 12 weekly sessions lasting 60 to 90 minutes. CBT can be administered either as group or individual therapy.2,17,22,23 It has both specific and nonspecific (i.e., more general or mixed) types; three specific types are described below.
Cognitive therapy is used to describe interventions that are largely based on the cognitive model, which states that an individual’s perception of a situation influences his or her emotional response to it. The general goal of cognitive therapy is to help people identify distorted thinking and to modify existing beliefs, so that they are better able to cope and change problematic behaviors. Cognitive therapy is generally considered to be brief, goal oriented, and time limited. Variants of cognitive therapy have been developed. Among these are cognitive restructuring and cognitive processing therapy.
Cognitive processing therapy includes psychoeducation, written accounts about the traumatic event, and cognitive restructuring addressing the beliefs about the event’s meaning and the implications of the trauma for one’s life.24 The treatment is based on the idea that affective states, such as depressed mood, can interfere with emotional and cognitive processing of the trauma memory, which can lead to traumatic symptomatology. The manualized treatment is generally delivered over 12 sessions lasting 60 to 90 minutes.24 (A manualized treatment is based on a guidebook that defines the specific procedures and tactics used to implement the treatment; the use of a manual facilitates standardization of a therapy across settings and therapists.)
Cognitive restructuring is based on the theory that the interpretation of the event, rather than the event itself, determines an individual’s mood. It aims to facilitate relearning thoughts and beliefs generated from a traumatic event, to increase awareness of dysfunctional trauma-related thoughts, and to correct or replace those thoughts with more adaptive and rational cognitions. Cognitive restructuring generally takes place over 8 to 12 sessions of 60 to 90 minutes.2,17
Coping skills therapies may include components such as stress inoculation training, assertiveness training, biofeedback (including brainwave neurofeedback), or relaxation training. These therapies may use techniques such as education, muscle relaxation training, breathing retraining, role playing, or similar interventions to manage anxiety or correct misunderstandings that developed at the time of trauma. The therapy is designed to increase coping skills for current situations. Most types of coping skills therapies require at least eight sessions of 60 to 90 minutes; more comprehensive interventions such as stress inoculation training require 10 to 14 sessions.2,17 Of note, this category includes a range of active psychotherapeutic treatments (e.g., stress inoculation training) and some comparison treatments that are generally intended as a control group (e.g., relaxation). Consequently, in this report we do not attempt to determine any overall effect for this category (as one would not have sufficient clinical relevance); rather we determine results separately for the various therapies we have included in this category. In addition, not all of these coping skills are CBT—for example, a CBT protocol might include relaxation training, but relaxation is not exclusively CBT.
Exposure-based therapy involves confrontation with frightening stimuli related to the trauma and is continued until anxiety is reduced. Imaginal exposure uses mental imagery from memory or introduced in scenes presented to the patient by the therapist. In some cases, exposure is to the actual scene or similar events in life: in vivo exposure involves confronting real life situations that provoke anxiety and are avoided because of their association with the traumatic event (e.g., avoidance of tall buildings following experiencing an earthquake). The aim is to extinguish the conditioned emotional response to traumatic stimuli. By learning that nothing “bad” will happen during a traumatic event, the patient experiences less anxiety when confronted by stimuli related to the trauma and reduces or eliminates avoidance of feared situations. Exposure therapy is typically conducted for 8 to 12 weekly or biweekly sessions lasting 60 to 90 minutes.2,10,17 Prolonged exposure is a manualized intervention including both imaginal and in vivo exposure components. 25
In this report, we include a category for CBT-mixed therapies for studies of interventions that use components of CBT, but that don’t quite fit cleanly into one of the other categories. The interventions in this category are somewhat heterogeneous in several ways, including how the authors defined and described “cognitive behavioral therapy.” Elements of CBT-mixed interventions may include psychoeducation, self-monitoring, stress management, relaxation training, skills training, exposure (imaginal, in vivo, or both), cognitive restructuring, guided imagery, mindfulness training, breathing retraining, crisis/safety planning, and relapse prevention. The studies varied as to how many sessions (if any) were dedicated to these elements and whether homework was assigned as part of the intervention.
In EMDR the patient is asked to hold the distressing image in mind, along with the associated negative cognition and bodily sensations, while engaging in saccadic eye movements. After approximately 20 seconds, the therapist asks the patient to “blank it out,” take a deep breath, and note any changes occurring in the image, sensations, thoughts, or emotions. The process is repeated until desensitization has occurred (i.e., patient reports little or no distress on the Subjective Units of Distress Scale), at which time the patient is asked to hold in mind a previously identified positive cognition, while engaging in saccadic eye movements, and rating the validity of this cognition while going through the procedure as outlined above. The saccadic eye movements were initially theorized to both interfere with working memory and elicit an orienting response, which lowers emotional arousal so that the trauma can be resolved. Although earlier versions of EMDR consisted of 1 to 3 sessions, current standards consist of 8 to 12 weekly 90-minute sessions.2,22
Hypnosis may be used as an adjunct to psychodynamic, cognitive-behavioral, or other therapies. It has been shown to enhance their efficacy for many clinical conditions.2,17 Number and length of sessions vary widely.
Interpersonal therapy is a time-limited, dynamically informed psychotherapy that aims to alleviate patients’ suffering and improve their interpersonal functioning. This type of therapy focuses specifically on interpersonal relationships; its goal is to help patients either improve their interpersonal relationships or change their expectations about them. In addition, it aims to help patients improve their social support so they can better manage their current interpersonal distress. Interpersonal therapy generally requires 10 to 20 weekly sessions in the “acute phase” followed by a time-unlimited “maintenance phase.”26
Psychodynamic therapy explores the psychological meaning of a traumatic event. The goal is to bring unconscious memories into conscious awareness so that PTSD symptoms are reduced. The therapy presumes that the PTSD symptoms are the result of the unconscious memories. Psychodynamic therapy traditionally lasts from 3 months to 7 years.2,17,22
Pharmacological Interventions
Pharmacotherapies, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, other second-generation antidepressants, atypical antipsychotics, anticonvulsants or mood stabilizers, adrenergic agents, benzodiazepines, and other treatments such as naltrexone, cycloserine, and inositol have been studied for treatment of patients with PTSD.2 Specific medications within these drug classes that have been studied or used in treating PTSD are listed in Table 2. Currently, only paroxetine and sertraline are approved by the U.S. Food and Drug Administration for treatment of patients with PTSD.
Table 2
Medications that have been used or studied for adults with PTSD.
Existing Guidance
Numerous organizations have produced guidelines for the treatment of patients with PTSD, including the American Psychiatric Association (APA), the U.S. Department of Veterans Affairs (VA)/Department of Defense (DoD), the United Kingdom’s National Institute for Health and Clinical Excellence (NICE), ISTSS, the IOM, the American Academy of Child and Adolescent Psychiatry (AACAP), and the Australian National Health and Medical Research Council (NHMRC).12 Four of these guidelines (VA/DoD, NICE, NHMRC, IOM) were based on systematic reviews; the other three guidelines (APA, ISTSS, AACAP) were based on expert consensus and less structured literature reviews.12
All of the existing guidelines agree that trauma-focused psychological interventions are effective, empirically supported first-line treatments for PTSD.12–15,17 Four of the six guidelines (VA/DoD, NICE, NHMRC, and ISTSS) give the strongest level of recommendation for EMDR; the APA guideline gives a second-level recommendation for EMDR, and the IOM guidelines conclude that the evidence is inadequate to determine the efficacy of EMDR, owing to methodological limitations and conflicting findings in the published studies.
There is less agreement in the guidelines about the effectiveness of pharmacotherapy. For example, three of the six guidelines (VA/DoD, APA, ISTSS) give SSRIs the strongest level of recommendation, two guidelines (NICE, NHMRC) give them a second-level recommendation, and one (IOM) concluded that the evidence was insufficient to determine the efficacy of SSRIs and other medications for the treatment of PTSD.
Guidelines have arrived at different conclusions about the efficacy of certain classes of treatment or specific treatments, possibly because of differences in selection criteria and methods used to assess risk of bias of the existing literature. For example, based on its evaluation of attrition rates and handling of missing data, the IOM Committee on the Treatment of PTSD concluded that the evidence on specific pharmacological drugs was inadequate to determine efficacy.2 The VA/DoD clinical practice guideline, which included some trials that the IOM considered to be flawed, concluded that SSRIs have substantial benefit; and some other agents offer some benefit for PTSD treatment.13 Of the 14 studies included by the IOM Committee to evaluate the efficacy of SSRI antidepressants, 7 were considered to have major limitations due to high attrition and/or the methods they used to deal with missing data.
As a result of differences in guideline recommendations, some clinical uncertainty exists about what treatment to select among all the evidence-based approaches, particularly when trauma-focused psychological therapy is unavailable or unacceptable to the patient. In addition to the clinical uncertainty about the effectiveness of some of the psychological treatments, the effectiveness and potential harms of medications for PTSD are uncertain. Furthermore, patient preferences need to be incorporated into shared decisionmaking about treatment because they can influence treatment adherence and therapeutic response.
Scope and Key Questions
A member of the American Psychological Association nominated this topic and the Agency for Healthcare Research and Quality (AHRQ) selected it through the topic prioritization process. Highlighting the timeliness and relevance of this topic, the IOM and various Federal agencies (e.g., the VA Health Administration) have identified PTSD as a priority area for quality improvement and comparative effectiveness research; these decisions are based, in part, on evidence of higher rates of PTSD among service members returning from operations in Afghanistan and Iraq than previously reported and their increased need for mental health services.9
We approach each key question by considering the relevant Populations, Interventions, Comparators, Outcomes, Timing, and Settings (PICOTS). Our report focuses on clinically relevant medications (those that are commonly used, those with sufficient literature for systematic review, and those of greatest interest to the developers of clinical practice guidelines). Further, we also address the clinical importance of moderators or subgroups of patients receiving PTSD treatment, as the evidence allows, such as differences by gender, comorbidities, refugee status, and military, VA, or civilian status. Our report is limited to people with a diagnosis of PTSD; it does not address those at risk of developing PTSD or interventions to prevent the development of PTSD.
The main objective of this report is to conduct a systematic review and meta-analysis of the comparative effectiveness and harms of psychological and pharmacological interventions for adults with PTSD. In this review, we address the following Key Questions (KQs):
- KQ 1.
What is the comparative effectiveness of different psychological treatments for adults diagnosed with PTSD?
- KQ 2.
What is the comparative effectiveness of different pharmacological treatments for adults diagnosed with PTSD?
- KQ 3.
What is the comparative effectiveness of different psychological treatments versus pharmacological treatments for adults diagnosed with PTSD?
- KQ 4.
How do combinations of psychological treatments and pharmacological treatments (e.g., CBT plus paroxetine) compare with either one alone (i.e., one psychological or one pharmacological treatment)?
- KQ 5.
Are any of the treatment approaches for PTSD more effective than other approaches for victims of particular types of trauma?
- KQ 6.
What adverse effects are associated with treatments for adults diagnosed with PTSD?
Analytic Framework
We developed an analytic framework to guide the systematic review process (Figure 1). The population consists of adult patients with a diagnosis of PTSD. Because we wanted to assess whether the evidence suggested any differences in response to various treatments for trauma subgroups, such as military personnel and those with comorbid psychiatric or medical conditions, we identified subgroups of interest as noted in the figure.
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
For each of the first five KQs, the same outcomes of interest are considered. KQ 1 compares the evidence of effectiveness of psychological interventions for improving these outcomes. KQ 2 examines the evidence of effectiveness of pharmacological treatments, considering both strategies that compare a single agent versus another single agent, as well as those that compare augmenting an ongoing treatment with one versus another pharmacological intervention. KQ 3 examines the direct evidence comparing various psychological treatments with pharmacological treatments. KQ 4 considers the evidence comparing combinations of psychological and pharmacological treatments with a single treatment intervention (either one psychological or one pharmacological treatment). KQ 5 considers specific subtypes of trauma, and assesses whether any particular treatment approach is more effective than another for that particular trauma subtype. KQ 6 compares the adverse events associated with the various interventions of interest.
- Introduction - Psychological and Pharmacological Treatments for Adults With Post...Introduction - Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD)
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