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Committee on the Assessment of Ongoing Effects in the Treatment of Posttraumatic Stress Disorder; Institute of Medicine. Treatment for Posttraumatic Stress Disorder in Military and Veteran Populations: Initial Assessment. Washington (DC): National Academies Press (US); 2012 Jul 13.
Treatment for Posttraumatic Stress Disorder in Military and Veteran Populations: Initial Assessment.
Show detailsThis chapter provides critical reviews of the various approaches to treatment for chronic posttraumatic stress disorder (PTSD), that is, PTSD lasting more than 3 months, although many of the treatments may be used with patients who suffer from acute PTSD (lasting more than 1 month and less than 3 months) and even those who have symptoms within 2 weeks after a traumatic event. The chapter begins with a description of the many psychosocial therapies whose efficacy is supported by an established evidence base—randomized controlled trials (RCTs). Among the psychosocial treatments discussed are exposure therapy, cognitive therapy, and group therapy. That is followed by a discussion of treatments that have been studied in open trials and for which RCTs have not been conducted. The efficacy of pharmacotherapy for PTSD is then considered, including the use of antidepressants—serotonin reuptake inhibitors (SRIs) and others— and the use of multiple drugs for PTSD and comorbid conditions. The efficacy of combinations of cognitive behavioral therapy and pharmacotherapy for PTSD is also discussed. The committee then looks at emerging treatments that are being used or being considered for use in the management of PTSD. These include manualized treatments (that is, those that have a manual of instructions) such as couple psychotherapy in which one or both persons have PTSD, and complementary and alternative medicine (CAM) treatments, most of which do not have a structured manual, such as yoga, acupuncture, and animal-assisted therapy. A synopsis of the many PTSD treatment guidelines is then given, including the Department of Veterans Affairs (VA)/Department of Defense (DoD) guideline for the management of posttraumatic stress that might assist the health care provider in selecting a treatment plan for a patient with PTSD.
There are numerous interventions for chronic PTSD, and not all of them have a robust database to support their efficacy for ameliorating PTSD symptoms. Not having RCTs supporting a particular treatment does not necessarily mean that it is not effective. The committee believes it is prudent to offer treatment supported by robust evidence before offering treatments that are not so supported. It should be noted that many of the treatments discussed in this chapter, even those with a robust body of evidence, may not have been tested specifically on military personnel who had PTSD, but in the absence of a well-reasoned argument against it, it is safe to hypothesize that treatments that were effective in well-controlled studies of a variety of civilian populations that had PTSD will also be effective in military personnel.
Not all people who have PTSD respond satisfactorily to initial treatment, and many remain treatment-resistant to varied degrees. Some guidelines offer recommendations on levels of care or stages of treatment in the event that the first evidence-based approaches fail to produce a satisfactory response. There is no widely accepted definition of what constitutes satisfactory response. Some studies use at least a 50% reduction in PTSD symptoms to indicate a satisfactory response; another indicator of a satisfactory response is a score of 15 on the Posttraumatic Stress Diagnostic Inventory to indicate subclinical PTSD severity and a score of 10 to indicate remission (Foa et al., 1993). On the Clinician-Assisted PTSD Scale (CAPS), subclinical PTSD is indicated by a score of 50, and remission by a score of 20 or less (Tucker et al., 2001). The percentage of responders varies among studies, types of traumas, definitions of response, magnitudes of intent to treat, and completer analyses. Depending on the specific cognitive behavioral treatment and the study sample, the percentage of responders can be as high as 90% and as low as 50% (Kar, 2011), and treatment outcomes are stable over time (e.g., Foa et al., 2005).
The evidence base for the best second- and third-line line treatment approaches for PTSD falls substantially, and more reliance is placed on expert opinion rather than empirical information. Examples of those treatments are antidepressants or use of an antipsychotic drug with a selective serotonin reuptake inhibitor (SSRI) in cases of partial SSRI response, watchful waiting for the first 4 weeks after trauma for those who have mild symptoms, but brief cognitive behavioral therapy (CBT) even within the first month in more severe cases.
PSYCHOSOCIAL TREATMENTS FOR CHRONIC PTSD
This section describes the psychosocial treatments whose efficacy has been examined in RCTs. A review of treatments whose efficacy has been examined in open trials follows, and finally, treatments that have been suggested but whose efficacy has not been examined are briefly described.
Treatments Supported in Randomized Controlled Trials
The vast majority of treatments that have been examined via RCT are in the general group of psychosocial therapies called cognitive behavioral therapy. They include exposure therapies, stress inoculation training or anxiety-management programs, and cognitive therapies. Many treatment programs combine components of each of those general treatment groups, and CBT has become an overarching concept that includes variants of exposure therapy, stress inculcation training, cognitive therapies, and their combinations.
Exposure Therapies
Exposure therapies are designed to reduce PTSD symptoms and related problems (such as depression, anger, and guilt) by helping patients to confront their trauma-related situations, memories, and feelings. Exposure interventions include imaginal exposure, which consists of repeated revisiting of the traumatic memory, and in vivo exposure, which involves confronting feared situations that are objectively safe. Treatment programs that include both kinds of exposure, such as prolonged exposure (PE), tend to produce better outcomes than programs that consist of only one of the components (e.g., Bryant et al., 2008).
Many RCTs have consistently shown that several exposure therapy protocols for PTSD are effective, and they have been recommended as a first-line treatment for PTSD by several treatment guidelines, such as the National Institute for Health and Clinical Excellence (NICE) and Australian National Health and Medical Research Council guidelines.
The most commonly used exposure protocol is PE (Foa et al., 2007). PE is based on emotional-processing theory (Foa and Kozak, 1986), which posits that anxiety disorders, including PTSD, reflect specific pathologic fears of places, situations, or objects that are safe but are perceived as dangerous, and therefore, are avoided (Foa and Cahill, 2001). PE is designed to modify PTSD sufferers’ typical erroneous perceptions that “The world is an utterly dangerous place” and “I am completely incompetent and unable to cope with stress.” The central components of PE are in vivo exposure and imaginal exposure. In vivo exposure consists of having the patient gradually and systematically approach situations, places, and people that he or she has been avoiding. Through repeated exposure to those stimuli, the dysfunctional, unrealistic expectations of harm are disconfirmed, and the patient experiences a reduction in the associated fear response. Imaginal exposure involves revisiting the memory in imagination and recounting the traumatic event in a way that promotes emotional engagement with the trauma memory and then processing the revisiting experience. Processing provides an opportunity for patients to examine their beliefs related to the trauma memory and to gain a new perspective on the trauma. Like in vivo exposure, repeated, prolonged imaginal exposure provides information that disconfirms dysfunctional erroneous cognitions and reduces the distress associated with confronting the memory. Psychoeducation and controlled-breathing exercises play a secondary role in PE. Psychoeducation comprises a discussion about what maintains PTSD and the reactions that commonly follow a trauma; controlled-breathing training is designed to lower a person’s baseline level of anxiety, which might have become heightened in part by rapid and shallow breathing. Treatment commonly consists of 8 to 12 sessions of 60–90 minutes each.
Many RCTs—the largest number of such trials of any psychosocial treatment for PTSD—indicate that PE effectively reduces PTSD symptoms in a variety of populations (such as female rape survivors, male and female veterans, and refugees; see Cahill et al., 2009, for a full review). PE is effective for both chronic PTSD (e.g., Foa et al., 1999a, 2005; Resick et al., 2002) and acute stress disorder (Bryant et al., 1999; Foa et al., 1995, 2006). Patients treated with PE generally maintain their gains at follow-ups of a year or more (e.g., Foa et al., 2005; Resick et al., 2002). In addition, PE consistently has been associated with rapid change and maintenance of large effect sizes over time (e.g., Foa et al., 2005). A recently published long-term follow-up study of civilians treated with cognitive processing therapy and PE indicated about 80% of participants were treated to the point of remission at the posttreatment point and remained in remission for 5–10 years after the end of treatment (Resick et al., 2011).
PE produces significantly greater pretreatment to posttreatment reductions in PTSD symptoms than supportive counseling (Bryant et al., 2003; Schnurr et al., 2007), relaxation training (Marks et al., 1998; Taylor et al., 2003; Vaughan et al., 1994), and treatment-as-usual, including pharmaco-therapy (Asukai et al., 2010), nonexposure-based individual psychotherapy (Boudewyns and Hyer, 1990), and combinations of psychopharmacology, counseling, and group therapy (e.g., Nacasch et al., 2010).
A similar protocol that includes both imaginal and in vivo exposure was developed by Marks et al. (1998). Imaginal exposure is conducted in the first half of the treatment and in vivo exposure in the second half. Only two RCTs used this protocol: Marks et al. (1998) and Taylor et al. (2003). Because of the similarity between the Foa et al. and Marks et al. protocols, the committee does not distinguish between them in this section.
Other Forms of Exposure Therapy
Variations of exposure therapy have been shown to be efficacious in RCTs. For example, Resick et al. (2008) compared cognitive processing therapy (CPT), which includes cognitive therapy and written exposure, with written exposure of the traumatic memory only and without the cognitive component of CPT without writing (see “Cognitive Therapies” section). Written exposure consisted of two preparatory sessions followed by five 2-hour sessions in which the patient was asked to write for about 60 minutes alone about his or her experienced trauma and then to read the narrative to the therapist, who provided unstructured supportive feedback. The written-exposure group did nearly as well as the group that had CPT with and without writing; at the 6-month follow-up, there was no significant difference between the groups. Van Emmerik et al. (2008) also found that structured writing therapy was as efficacious as cognitive therapy in treatment for PTSD.
Exposure in the context of a broader narration of the patient’s life also has empirical support. For example, narrative exposure therapy, a brief manualized treatment, has been shown to be efficacious for treating PTSD in war-ravaged refugee populations (Neuner et al., 2008). A variation of this treatment is testimony therapy, which is a brief nonmanualized individual intervention designed for survivors of war; however, the only RCT found no difference between this treatment and wait list (WL) both soon after and 11 months after treatment (Igreja et al., 2006).
Blanchard et al. (2003) developed CBT–MVA (motor vehicle accident), a short-term manualized exposure therapy protocol that targets victims of motor vehicle incidents who have PTSD. CBT–MVA includes in vivo exposure, progressive muscle relaxation, cognitive restructuring, one session of couple therapy (if the patient has a spouse) and one session focusing on anger or existential issues stemming from the incident. In an RCT, patients who received CBT–MVA reported greater reductions in PTSD symptoms than patients who received supportive psychotherapy, who in turn reported greater reductions in PTSD than those on WL. Gains made in the two treatment groups were maintained at 3 months.
Imagery rescripting (Smucker et al., 1995) is another exposure therapy protocol that has been examined in RCTs both as an addendum to PE and as a stand-alone therapy for victims of childhood sexual abuse. The patient first engages in an imaginal exposure, immediately followed by a rescripting, in which the patient is encouraged to revisit the trauma while developing mastery imagery by imagining himself or herself as an adult entering the room during the trauma and rescuing and protecting the vulnerable child (Cukor et al., 2009). An RCT compared imaginal exposure coupled with imagery rescripting with imagery rescripting alone and found that both groups experienced improvement in PTSD symptoms with those on WL. There were no differences between the two treatment groups (Arntz et al., 2007).
McLean and Foa (2011) reviewed the evidence base for exposure therapy. Several meta-analyses of exposure therapy (e.g., Bradley et al., 2005) have found that it is far more effective than WL or supportive therapy and as effective as SSRIs in the short-term with lower dropout rates, but data on long-term effects are sparse (Van Etten and Taylor, 1998). Other meta-analyses have shown that exposure therapy is more effective than “non–trauma-focused” treatments or WL in reducing PTSD symptoms, but the differences in outcomes among the different exposure therapies was not significant (Bisson and Andrew, 2007; Seidler and Wagner, 2006). A recent meta-analysis of 13 PE studies found a large effect size for PE compared with WL or psychological placebo immediately after treatment that was maintained at follow-up (Powers et al., 2010). Studies have also shown that PE leads to significantly greater pretreatment to posttreatment reductions in PTSD symptoms than supportive counseling (Bryant et al., 2003; Schnurr et al., 2007), relaxation (Marks et al., 1998; Taylor et al., 2003; Vaughan et al., 1994), and treatment-as-usual (Asukai et al., 2010; Boudewyns and Hyer, 1990; Cooper and Clum, 1989; Nacasch et al., 2010). Furthermore, comparative treatment studies have found PE to be of at least comparable efficacy with other forms of CBTs, such as stress inoculation training (SIT), CPT, cognitive therapy (CT), and eye movement and desensitization reprocessing (EMDR) (Bryant et al., 2003, 2008; Foa et al., 1991, 1999a, 2005; Marks et al., 1998; Paunovic and Ost, 2001; Power et al., 2002; Resick et al., 2002, 2008; Rothbaum et al., 2005; Schnurr et al., 2001; Tarrier et al., 1999; van Emmerik et al., 2008; see Powers et al., 2010, for meta-analytic review of these findings). Finally, adding SIT or CT to PE has little benefit (Foa et al., 1999a, 2005).
In a comprehensive review of RCTs for exposure therapy for PTSD, an Institute of Medicine (IOM) committee looked at 23 studies, 8 of which met the committee’s quality criteria for inclusion in its assessment. These studies demonstrated a statistically significant improvement in patients receiving exposure therapy based on a primary PTSD scale or loss of a diagnosis of PTSD. The committee found that “the evidence is sufficient to conclude the efficacy of exposure therapies in the treatment of PTSD” (IOM, 2008).
In conclusion, there is strong evidence of the efficacy and effectiveness of variants of exposure therapy, in particular PE, in different trauma populations on the basis of studies conducted in independent centers around the world. Treatment benefits have been maintained at 5–10 years follow-up (Resick et al., 2011). Exposure therapy has also been successfully disseminated among community therapists in individual clinics in the United States and other countries and in large mental health systems, such as that of the VA.
Cognitive Therapies
CT (Beck et al., 2005) is a treatment protocol in which the therapist helps the patient to identify and modify the negative thoughts and beliefs that are considered to underlie pathologic emotions and behaviors. In PTSD treatment, the target is thoughts and beliefs related to a traumatic experience (for example, survival guilt, self-blame for causing the trauma, feelings of personal inadequacy, or worries about the future) with the goal of modifying them to reduce PTSD symptoms and improve mood and functioning. In several RCTs, CT alone has been shown to be an effective intervention for patients who have PTSD with significant reductions in PTSD symptoms (Cottraux et al., 2008; Marks et al., 1998; Resick et al., 2008; Tarrier et al., 1999).
CPT (Resick et al., 2002) is a manualized treatment that combines aspects of CT and PE. It consists of four components: education about specific PTSD symptoms and how the treatment can be beneficial, increasing the patient’s awareness of his or her thoughts and feelings, learning skills to help patients question or challenge maladaptive thoughts, and understanding that experiencing a trauma can change a person’s beliefs about the world and relationships. The aim of CPT is to help patients find a better balance between the beliefs they had before and after their trauma. The treatment program consists of 12 1-hour sessions delivered over 6 weeks. The original protocol included an exposure component in the form of repeated writing of the traumatic memory and reading of it to the therapist.
Resick et al. (2008) disentangled the effects of the cognitive component of CPT and the component of writing and reading of the traumatic memory by comparing three groups: full CPT protocol, CT without writing, and writing alone. Although patients in all three groups showed substantial improvement, CT alone showed greater reduction in PTSD symptoms than writing alone. However, at the end of treatment there was no superiority to CPT with and without writing, and writing and reading alone were almost as efficacious as the other two protocols. The writing and reading protocol requires much less therapist training than CPT and seems to be less expensive. Resick is examining the efficacy of group and individual CPT in military personnel.
Elhers and Clark (2000) have developed a CT protocol for PTSD that is based on their cognitive model of PTSD. The protocol focuses on modifying negative thoughts about the trauma and its consequences, reducing re-experiencing by elaboration of the trauma memories and identification of triggers, and encouraging patients to stop dysfunctional behaviors and cognitive strategies. CT also uses in vivo and imaginal exposure. This treatment has been evaluated in two RCTs (Ehlers et al., 2003, 2005), both of which found it to be efficacious.
Kubany et al. (2003) developed a specific CT protocol for female victims of spousal violence. Cognitive trauma therapy for battered women who have PTSD is a manualized short-term treatment that includes a number of treatment elements adapted from other CBTs for PTSD—including psychoeducation about PTSD, stress management (including relaxation training), and exposure—and other techniques, including reducing irrational guilt-related beliefs and negative self-talk by the women about guilt and shame. Two RCTs that compared cognitive trauma therapy for battered women to WL found that patients who received the treatment experienced large reductions in PTSD symptoms, depression, and guilt, and increases in self-esteem (Kubany et al., 2003, 2004).
In conclusion, variants of CT have received support for their efficacy through well-controlled studies. However, the number of studies of each treatment program is small compared with exposure therapy.
Eye Movement Desensitization and Reprocessing
EMDR (Shapiro, 1989a, b) is a manualized treatment to assist patients in accessing and processing traumatic memories while bringing them to an adaptive resolution (Shapiro, 2001). The patient is asked to access a disturbing image associated with the traumatic event, solicit the experience of body sensations associated with the image, identify a negative self-referring belief, and identify a preferred positive belief to replace the negative belief. The patient is then asked to hold the disturbing image, sensations, and the negative belief or thought in mind while tracking the clinician’s moving finger back and forth in front of his or her visual field for about 20 seconds. This process is repeated until the patient has no negative associations with the targeted image.
Results of four RCTs suggest that EMDR is an efficacious treatment for PTSD. Lee et al. (2002) and Power et al. (2002) found that its results were equivalent to those of CBT. Taylor et al. (2003) found PE to be more effective than EMDR and relaxation training; moreover, PE, but not EMDR, was significantly more efficacious than relaxation (the control condition). Rothbaum et al. (2005) found that in a 6-month follow-up a significantly larger fraction of patients who received PE were responders than of those who received EMDR.
Several studies (e.g., Davidson and Parker, 2001; Spates et al., 2009) have examined the relative contribution of the eye-movement component and found no effects of its efficacy. Consequently, some PTSD treatment experts posit that the efficacy of EMDR is due to the exposure component that it shares with other existing, successful treatments, such as PE. An IOM committee that critically assessed four RCTs for EMDR concluded that the evidence was inadequate to determine its efficacy for the treatment of PTSD (IOM, 2008).
Imagery Rehearsal Therapy
Imagery rehearsal therapy (IRT) targets the nightmares that are a common symptom of PTSD by changing the content of a patient’s nightmares to promote mastery over the content threat, thereby altering the meaning and importance of and orientation to the nightmares. In a small RCT, Krakow et al. (2001) compared IRT and WL and found that among treatment completers, participants who received IRT had a larger reduction in self-reported PTSD severity at the 3-month follow-up, the impact of their nightmares was reduced, and their sleep quality improved. However, a recent large RCT comparing IRT with a group nightmare-management treatment in Vietnam veterans with PTSD found that neither treatment produced significant or sustainable improvement in overall PTSD symptom severity, nightmare frequency, or sleep quality (Cook et al., 2010). Thus, although IRT has empirical support as being an effective treatment for nightmares, its efficacy as a treatment for PTSD is questionable.
Psychodynamic Psychotherapy
Brom et al. (1989) conducted an RCT to compare the efficacy of Horowitz’s (1976) brief psychodynamic therapy, which focuses on solving intrapsychic conflicts that result from a traumatic experience, with hypnotherapy, trauma desensitization, and a WL control group. Not all study participants met the criteria for PTSD. Re-experiencing and avoidance symptoms improved significantly in all treatment groups but not in the WL group; no differences were found among the three treatments.
Brief Eclectic Psychotherapy
Gersons et al. (2000) developed manualized brief eclectic psychotherapy, which includes imaginal exposure combined with relaxation, writing assignments, use of mementos of the traumatic experience, exploration of meaning, a farewell ritual, and psychoeducation. Significant reductions in PTSD symptoms and anxiety symptoms were detected compared with the result of WL in an RCT of 42 police officers after the 16 sessions and at 3-month follow-up. It is unclear which of the several treatment components are responsible for the improved outcomes. Lindauer et al. (2005) conducted an RCT with 24 patients and found that brief eclectic psychotherapy resulted in a reduction in PTSD and symptoms of general anxiety compared with WL.
Hypnosis
Hypnosis is defined as a heightened state of relaxation during which a health professional or researcher guides a person with suggestions for experiencing changes in sensations, perceptions, thoughts, or behaviors (Everly and Lating, 2004). Hypnotic techniques have been used as an adjunctive therapy focusing on nightmares and insomnia in PTSD (Kirsch, 1999; Spiegel and Spiegel, 1987). Brom et al. (1989) found hypnosis to decrease intrusive symptoms more than WL, but not all research participants met the criteria for PTSD. Abramowitz et al. (2008) compared hypnotherapy with the use of zolpidem in an RCT of veterans who had combat PTSD and insomnia. All patients were already taking an SSRI. Hypnotherapy improved PTSD symptoms, sleep quality, and ability to concentrate more than zolpidem did.
Relaxation
Three RCTs have examined the efficacy of relaxation used in control groups in the study of imaginal exposure, EMDR, PE, or CT (Marks et al., 1998; Taylor et al., 2003; Vaughan et al., 1994). The results of the studies suggest that relaxation has at best a moderate effect on PTSD symptoms, but it is not as effective as exposure or cognitive therapy.
Stress Inoculation Training
SIT (Meichenbaum, 1974) was developed as an anxiety-management treatment and has been modified to treat rape victims (Kilpatrick et al., 1982). SIT includes relaxation training, breathing retraining, positive thinking and self-talk, assertiveness training, and thought stopping (Foa et al. 1999b). Some SIT protocols also include cognitive restructuring and exposure therapy. Two studies have compared the efficacy of SIT in the treatment of female sexual assault victims who had PTSD with the efficacy of PE, supportive counseling, and WL (Foa et al., 1991) and with the efficacy of SIT plus PE (Foa et al., 1999a). Both studies found SIT to be more effective than WL in reducing PTSD and related symptoms and to be of comparable efficacy to PE on some measures. Chemtob et al. (1997) found that SIT was more effective than anger management and treatment-as-usual in reducing anger and re-experiencing of symptoms.
Interpersonal Therapy
Interpersonal therapy (IPT) is a manualized time-limited structured psychotherapy. Targeted IPT interventions seek to improve distressing interpersonal problems (role conflict, role transition, and loss) and thus to lead to greater social support with consequent benefits regarding mood and anxiety. Because PTSD is often accompanied by problems with intimate familial relationships, it has been hypothesized that treatment that focuses on interpersonal concerns would lead to amelioration of PTSD symptoms.
A single RCT compared individual IPT with WL in a small sample of Sudanese refugees living in Cairo, Egypt (Meffert et al., 2011). The authors used conservative intent-to-treat analyses and found that IPT predicted a significant decrease in symptoms of PTSD, state anger, and depression.
Skills Training in Affect and Interpersonal Regulation
Cloitre et al. (2002) developed a two-phase treatment consisting of eight sessions of skills training in affect and interpersonal regulation (STAIR) followed by eight sessions of imaginal exposure. The two-phase combined treatment was more effective than WL in increasing emotional regulation and reducing PTSD. Imaginal exposure but not STAIR reduced PTSD symptoms; moreover, imaginal exposure increased emotional regulation as much as did STAIR despite being delivered at the second stage of treatment. In a follow-up study, Cloitre et al. (2010) compared the combination of STAIR and imaginal exposure with counseling and imaginal exposure. There was a tendency for STAIR and imaginal exposure to produce more recovery from PTSD, but the difference was not significant.
Behavior Activation
In small RCTs (Jakupcak et al., 2010; Wagner et al., 2007) and open trials (Nixon and Nearmy, 2011), behavioral activation has been shown to be an effective CBT intervention for PTSD, although more well-controlled studies are needed to determine efficacy. The primary goal of this model is to assist people in accessing their emotions and experiences while focusing on living a fulfilling life as opposed to avoiding and escaping pain (Hayes et al., 2006). The treatment is implemented in both groups and individuals. Five specific themes shape the manualized program: escape does not work effectively and leads to “creative helplessness,” efforts to control pain create struggles, people are separate from their thoughts, moving beyond the struggle for control is central, and moving toward a commitment to action that is consistent with world views and values. The model has been evaluated for its efficacy in several anxiety disorders, but at present there is no evidence of its efficacy for PTSD (Pull, 2009).
Group Therapy
A number of group-based treatments for PTSD that draw on efficacious individual therapies are associated with symptom improvement. One benefit of group treatments over individual treatment is the efficiency in provision of treatment; another is the potential of group members to give social support to each other, which is key for people who have PTSD, inasmuch as lack of social support is a known risk factor for PTSD (e.g., Brewin et al., 2000; Ozer et al., 2003).
Six RCTs have examined the efficacy of CBT group therapy approaches. Schnurr et al. (2003) investigated trauma-focused group therapy in male Vietnam veterans in a large and rigorous study. Trauma-focused group therapy is a manualized treatment (30 sessions) consisting of education about PTSD, coping resource assessment, and self-management of symptoms; writing of premilitary autobiographies; war zone scene identification, exposure, and cognitive restructuring; and relapse prevention. One-third of the sessions are devoted to individual work (Foy et al., 2002). In Schnurr et al. (2003), trauma-focused group therapy was compared with present-centered group therapy, an approach designed to provide nonspecific factors of support and interpersonal connection inherent in group treatment. The investigators found that both groups experienced significant modest pretreatment to posttreatment improvement in PTSD, which was maintained at 12 months. No differences between the groups were detected.
Rogers et al. (1999) compared a single session of flooding-based exposure group therapy with a single session of group EMDR in 12 Vietnam veterans in an inpatient setting. No differences were found between groups in PTSD symptoms after treatment, and both groups showed significant improvements.
Beck et al. (2009) randomized people who had motor vehicle incident-related PTSD to group CBT or a minimal-contact comparison group. The group CBT was a 14-week treatment adaptation of individual exposure-based CBT to a group setting. After treatment, group CBT had resulted in significantly greater reductions in PTSD symptoms in those who completed treatment. Furthermore, 88.3% of patients who received group CBT no longer had a diagnosis of PTSD compared with 31.3% of the patients in the minimal-contact group.
Two RCTs have compared different types of group CBT with WL, all involving female populations. Zlotnick et al. (1997) randomly assigned female survivors of childhood sexual abuse to either 15 weekly 2-hour group dialectical behavior therapy group sessions or WL. The group sessions comprised education and practice of various affect-management skills, including emotion identification, anger management, self-soothing, and distress tolerance. The group treatment resulted in significant reductions in self-reported PTSD severity and dissociation, compared with no change in the WL group. Finally, multiple channel exposure therapy—which incorporates PE, CPT, and interoceptive exposure for panic disorder—was found to be superior to a control group in women who have PTSD and comorbid panic attacks (Falsetti et al., 2005).
Two RCTs have examined non-CBT approaches with WL in women who had PTSD related to sexual abuse. Comparison of a WL group with a trauma-focused group and a present-focused group, both based on psy-chodynamic principles, showed no differences between either treatment and the WL group (Spiegel et al., 2004). However, Krupnick et al. (2008) conducted an RCT to compare group-based interpersonal treatment with WL and found that the treatment was significantly more effective in treating symptoms of PTSD and depression than was WL.
In summary, several studies of group therapy found it to be efficacious in reducing PTSD, but the reduction was modest. An IOM committee that reviewed four studies of group therapy concluded that the evidence was inadequate to determine the efficacy of group therapy formats for the treatment of PTSD, primarily due to the lack of well-designed studies comparing group and individual formats with an appropriate control group (IOM, 2008).
Treatments Studied in Open Trials
Virtual-Reality Exposure
Virtual-reality exposure (VRE) therapy uses real-time computer graphics and head-mounted visual displays as a tool to deliver PE. Users are provided with a relevant multisensory controlled-stimulus environment, and the clinician can systematically control the presence or absence of provocative stimuli delivered in the VR simulation to pace the level of exposure. Proponents of VRE assert that the use of VR in the context of PE can increase activation and modification of the fear structure more than can imaginal exposure without VR. They also assert that some patients who have “grown up digital” may be more likely to seek PE delivered in a technology–media format that they are familiar with from video games. To date, there is no evidence of the superiority of PE plus VRE to PE alone in patients who have PTSD, although preliminary data in support of the assertion that some patients are likely to seek PE when it is accompanied by VRE have been reported (Reger et al., 2009). Case studies suggest that the use of VRE is effective in reducing PTSD (Difede and Hoffman, 2002; Rothbaum and Hodges, 1999; Rothbaum et al., 2001) and more effective than WL (Difede et al., 2007), but no RCT has compared the efficacy of PE alone with that of VRE alone.
The virtual Iraq/Afghanistan VRE application (Rizzo et al., 2011) consists of a series of virtual scenarios that are designed to resemble the general contexts that most service members experience during deployment to Iraq or Afghanistan and that are used as digital contexts for delivering PE. Two early case reports showed positive results of the system (Gerardi et al., 2008; Reger and Gahm, 2008). Following those, an open clinical trial with 24 active-duty soldiers produced significant pretreatment to posttreatment reductions in PTSD Checklist–Military version scores with a large treatment effect size (Reger et al., 2011). After an average of seven sessions, 46% of those treated no longer screened positive for PTSD, and 62% had reliably improved. In a second open clinical trial, 20 active-duty Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) service members, who had previously received PTSD treatments (such as PE, group counseling, EMDR, and medication) without benefit, received an average of 11 VRE sessions. Of the treatment completers, 80% showed both statistically and clinically meaningful reductions in PTSD, anxiety, and depression symptoms. Patients reported improvements in their everyday life that were maintained at 3-months posttreatment (Rizzo et al., 2011). In contrast, a study that used a combined sample of active-duty soldiers who had undergone either VR or imaginal PE therapy showed only modest pretreatment to posttreatment gains on the CAPS although changes in functional magnetic resonance imaging brain responses to emotional stimuli suggest a positive response to treatment (Roy et al., 2010).
The U.S. Army is currently evaluating the efficacy of VRE compared with PE in RCTs, but no results have been reported at this time. Until the results from the four ongoing RCTs are available, there is insufficient evidence for the efficacy of the virtual Iraq/Afghanistan VRE in reducing PTSD symptoms.
Acceptance and Commitment Therapy
Acceptance and commitment therapy (ACT) is a behavior-based treatment that is grounded in the concept that suffering emerges from avoidance of pain rather than from a direct experience of pain. It is used in many VA medical centers to treat chronic PTSD. Walser and Westrup (2007) have published an ACT manual for the treatment of PTSD. Support for ACT is limited to a single case study by Twohig (2009), who treated a woman who had PTSD and depression and initially received 20 sessions of CBT that included written exposure and cognitive restructuring. The patient received 21 sessions of ACT and showed significant reduction in PTSD, depression, and anxiety in response to trauma-related thoughts by the end of treatment.
Helping to Overcome PTSD with Empowerment
Helping to Overcome PTSD with Empowerment (HOPE) is a short-term CBT treatment for battered women who have PTSD and are in domestic violence shelters (Johnson and Zlotnick, 2009). It is a manualized 9–12-session treatment that addresses the women’s needs (such as establishing safety, self-care, and protection; remembrance and mourning; and reconnection) while including such CBT components as cognitive restructuring and psychoeducation.
Metacognitive Therapy
Metacognitive therapy (Wells and Sembi, 2004a) is a brief, manual-ized, cognitive-based treatment that includes mindfulness and strategies to shift attention away from rumination and worry. Wells and Sembi (2004b) provided metacognitive therapy to five women and one man and found improvements in general emotion and specific PTSD measures that were maintained at follow-up (18–41 months).
Trauma Management Therapy
Trauma management therapy (Frueh et al., 1996) is a mixed individual and group therapy for veterans who have combat-related PTSD that focuses on such PTSD symptoms as social withdrawal, numbing, expression of anger, and interpersonal difficulties. The therapy combines intensive individual exposure therapy, programmed practice, and structured social and emotional skills training groups. In individual counseling sessions, psychoeducation and exposure therapy are given, followed by programmed practice at home that consists of exercises for controlling one’s own exposure; after this, a social and emotional rehabilitation phase begins. The latter phase is conducted in small groups of two to five veterans, and includes social skills training, anger management, and training on how to communicate to civilians about military issues. In one study of 15 veterans, Frueh et al. (1996) found that the 11 veterans who completed the program experienced significant improvement in anxiety, flashbacks, nightmares, sleep difficulty, heart rate reactivity, and overall social functioning.
Trauma Incident Reduction
Gerbode (1995) developed trauma incident reduction, in which the patient is initially instructed to revisit the traumatic event mentally without verbalizing it, and only then to follow it with a verbalization of the memory. Trauma incident reduction appears to be very similar to imaginal exposure. Support for trauma incident reduction for people who have PTSD consists mostly of case studies or case series (Carbonell and Figley, 1999; Figley et al., 1999).
PHARMACOTHERAPY
Medication has long been an integral part of the treatment for chronic PTSD. Sargant et al. (1972) noted that in the 1960s that tricyclic and monoamine oxidase inhibitor (MAOI) antidepressants were the most effective, and clinical trials have confirmed the accuracy of these observations. The authors saw medication as playing a primarily supportive role in which control of symptoms permitted patients to mobilize their own coping mechanisms. More recent neurobiological studies of PTSD and related disorders have indicated the relevance of various neurotransmitter systems—such as noradrenergic, dopaminergic, serotonergic, glutamatergic and GABAergic (producing gamma-aminobutyric acid) pathways—and the different drug groups that are now used to treat the disorders act mostly through these systems.
The main recommendations for the use of pharmacotherapy to treat chronic PTSD are based on whether medication is a first-line treatment for PTSD. The choice of a drug depends on the evidence base to support the choice and studies that support the treatment for specific problems in PTSD such as smoking cessation, sleep disturbances, and irritability.
The VA/DoD, International Society for Traumatic Stress Studies (ISTSS), American Psychiatric Association (APA), British Association of Psycho-pharmacology, World Federation of Societies of Biological Psychiatry, and International Psychopharmacology Algorithm Project (IPAP) guidelines (discussed later in this chapter) all recommend the use of an SSRI (such as paroxetine or sertraline) or the serotonin norepinephrine reuptake inhibitor (SNRI) antidepressant venlafaxine extended-release as a first choice, giving them the same status as psychotherapy. The UK and Australian guidelines recommend drug therapy only as a second choice unless the patient declines psychotherapy or manifests particular clinical features. An IOM report (2008) on treatments for PTSD concluded that neither SRIs nor any other drugs could be considered effective for treatment for PTSD although the committee’s conclusion was not unanimous. A Cochrane review (Stein et al., 2006) found that there was good evidence for SSRI and SNRI drugs in chronic PTSD as both short-term and maintenance treatment, and a subsequent meta-analysis of pharmacotherapies for PTSD also found that medication reduced PTSD symptom severity (Ipser and Stein, 2011). A meta-analysis of the effectiveness of pharmacotherapy compared with psychotherapy for the treatment of combat-related PTSD found that pharma-cotherapy resulted in a significantly greater decrease in PTSD symptoms from baseline than did psychotherapy within a 6-month timeframe, based on standardized scores (Stewart and Wrobel, 2009). Based on this analysis, the authors suggest that pharmacotherapy be considered as a first-line treatment for veterans who have combat-related PTSD, particularly those with severe symptoms. The following sections discuss the evidence supporting the use of various pharmacotherapies for PTSD.
Antidepressants
Tricyclics and Monoamine Oxidase Inhibitors (MAOIs)
Although these drugs are now perhaps underused, the first placebo-controlled RCTs of medication for PTSD found that the tricyclic drugs amitriptyline and imipramine, and the MAOI phenelzine, were more effective than placebo in veterans of World War II and Vietnam (Davidson et al., 1990; Kosten et al., 1991). Given the later difficulty of showing the efficacy of antidepressants in veteran populations, those positive findings deserve to be emphasized, especially because amitriptyline and imipramine, broad-spectrum drugs, also help to restore sleep and reduce pain. One study of desipramine was negative, but the treatment dose and duration may have been insufficient (Reist et al., 1989) and the drug’s selective effect only on norepinephrine may have been a limitation. Studies of the reversible MAOI class A have been disappointing (Baker et al., 1995; Katz et al., 1994).
Selective Serotonin Reuptake Inhibitors
Because of their greater safety and tolerability, SSRIs have largely replaced the older antidepressants in clinical practice, and there is reasonably strong evidence to support their use in PTSD on the basis of numerous placebo-controlled RCTs. Two drugs, sertraline (Brady et al., 2000, 2005; Davidson et al., 2001; Friedman et al., 2007) and paroxetine immediate-release (Marshall et al., 2001; Stein et al., 2003; Tucker et al., 2001), have been approved in the United States and some other countries for PTSD, and these two SSRIs have been the most extensively studied (e.g., Ipser and Stein, 2011; Stein et al., 2006; Zhang and Davidson, 2007) and cited in PTSD guidelines (APA, 2004; British Association of Psychopharmacology et al., 2005; IPAP, 2005; NCCMH and NICE, 2005). Ipser and Stein (2011) found evidence of efficacy for two of four SSRIs, sertraline and paroxetine, in their meta-analysis of pharmacotherapy for PTSD, with paroxetine being significantly more effective than the other SSRIs (P = 0.0001).
Although the VA/DoD guideline recommends SRIs as first-line treatment, this committee is unaware of any positive trials of this class of drugs conducted in U.S. veterans only. However, two placebo-controlled studies in foreign veterans demonstrated efficacy of SRI treatment for PTSD. In Bosnian War veterans, fluoxetine was substantially better than placebo (Martenyi et al., 2002b). An additional placebo-controlled RCT showed greater benefit of sertraline than of placebo in Iranian veterans of the Iran–Iraq war (Panahi et al., 2011). In a trial of sertraline compared with placebo exclusively in U.S. veterans, there was no difference between treatments (Friedman et al., 2007). In the main paroxetine reports (Marshall et al., 2001; Stein et al., 2003; Tucker et al., 2001), analysis of response by trauma type found that combat-related PTSD responded better to the drug than to placebo; however, the number of cases of combat-related PTSD in these studies was small, less than 10% of the total number of patients in each RCT.
There have been no placebo-controlled trials of the SSRIs fluvoxamine or escitalopram. There has been one negative trial of citalopram (Tucker et al., 2003), and although the VA/DoD guideline (2010) initially recommended its use, the VA and the DoD have recently issued a warning against using citalopram for persons with risks or predisposition to specific comor-bid heart conditions. One other SSRI, fluoxetine, has been extensively studied. Efficacy was demonstrated in some (Connor et al., 1999; Vanderkolk et al., 1994) but not all studies. A fixed-dose trial of fluoxedine at 20 mg and 40 mg failed to differ from placebo in a large group of women who had PTSD (Martenyi et al., 2007). Trials of fluoxetine in U.S. veterans have been negative (Hertzberg et al., 2000; Vanderkolk et al., 1994), and one in Bosnian War veterans was positive (Martenyi et al., 2002b). It is possible that the full benefits of SSRI drugs are not detected in standard RCTs; nevertheless, many clinicians in the VA and DoD health care systems still favor their use.
Serotonin-Norepinephrine Reuptake Inhibitors
There have been two positive trials of venlafaxine versus placebo: one in the United States (Davidson et al., 2006b) and one in other countries (Davidson et al., 2006a). In the U.S. study, sertraline was adopted as an active control and had the same results as the placebo. In the international study, the period of double-blind treatment extended to 6 months, and rates of remission increased further between 12 and 24 weeks: there was a significant drug effect on resilience. In a report of pooled data from the two studies, there was no difference between drug and placebo in subjects who had combat-related PTSD (Rothbaum et al., 2008a).
Other Antidepressants
Nefazodone had greater benefit than placebo in one study of U.S. veterans (Davis et al., 2004), and mirtazapine was found to be superior to placebo in nonveterans (Davidson et al., 2003). In veterans, bupropion was no different from placebo in PTSD, although it helped in achieving greater smoking cessation (Becker et al., 2007; Hertzberg et al., 2001). It may be relevant that the first two drugs affect both serotonin and norepinephrine and improve sleep, whereas bupropion, a selective dopamine and norepi-nephrine modulator, has minimal benefit on sleep.
Anticonvulsants
Four placebo-controlled trials have failed to show the benefit of la-motrigine, tiagabine, topiramate, or divalproex (Davidson et al., 2007; Davis et al., 2008a; Hertzberg et al., 1999; Tucker et al., 2007) for PTSD. The studies of lamotrigine and divalproex were conducted in veterans.
Antipsychotics
Monotherapy trials of atypical antipsychotic therapy versus placebo have yielded mixed results. They include a small negative trial of olanzap-ine in veterans (Butterfield et al., 2001) and two partially positive studies of risperidone in women who had PTSD stemming from childhood abuse (Padala et al., 2006; Reich et al., 2004): in one of these (Reich et al., 2004), almost half the sample were receiving other drugs. Quetiapine was found to be superior to placebo in a two-site trial of 80 veterans who had PTSD (Canive et al., 2009).
Several small initial augmentation RCTs of the antipsychotic drugs risperidone and olanzapine in veterans and civilians showed that the drugs reduced some symptoms of PTSD, particularly sleep disturbance (Bartzokis et al., 2005; Hamner et al., 2003; Monnelly et al., 2003; Rothbaum et al., 2008b; Stein et al., 2002), but the largest RCT, a 6-month study of risperi-done in veterans with combat-related PTSD was negative on the primary and most secondary outcome measures (Krystal et al., 2011). In the latter trial, differences favored risperidone for re-experiencing and hyperarousal symptoms, but according to the investigators, the size of this difference was not clinically meaningful. Questions remain about the effect of atypical antipsychotic augmentation in PTSD and whether between-drug differences are important. As with all treatments, side effects should be taken into account, and the issues surrounding the metabolic syndrome and abnormal movements are a concern with regard to antipsychotic drugs.
Benzodiazepines and Other GABAergic Drugs
One small study of alprazolam in people who have various types of trauma showed no advantage over placebo (Braun et al., 1990), and another small crossover study of clonazepam versus placebo in combat-related PTSD was also negative (Cates et al., 2004). However, Pollack et al. (2011) found a short-term improvement in overall PTSD severity and associated sleep disturbances in a small RCT of the non-benzodiazepine hypnotic drug eszopiclone in 24 civilians.
Benzodiazepines and some other drugs, such as beta blockers, might have the potential to impair positive coping after trauma or interfere with extinction of fear responses. However, the data have demonstrated through animal studies (Bouton et al., 1990) or single dose use in close proximity to psychotherapy that this is difficult to translate into everyday clinical situations.
Antiadrenergic Drugs
The alpha-1 adrenergic blocker prazosin has been shown to be more effective than placebo for reducing PTSD-associated sleep disturbances in three trials, two in veterans with combat-related chronic PTSD (Raskind et al., 2003, 2007) and one in civilians with PTSD (Taylor et al., 2006), all of whom had prominent sleep disruption or nightmares. More information is needed concerning the optimal dose of prazosin and interactions that may result from the concurrent use of other drugs. In a study of the antiadrenergic drug guanfacine, no benefit was found, but the population was not selected according to criteria of sleep disturbance (Neylan et al., 2006). A second study (Davis et al., 2008b) also failed to show a benefit of guanfacine over placebo. In animal studies, beta blockers such as pro-pranolol have been shown to reduce the consolidation of aversive memories significantly (for example, see Rodriguez-Romaguera et al., 2009). On the basis of those findings, the use of propranolol for the prevention of PTSD has been explored and has had mostly negative results (Pitman et al., 2002; Stein et al., 2007). Question remain about the use of antiadrenergic agents in the prevention of and treatment for PTSD.
Other Drugs
Negative studies have been published for the use of monotherapy with D-cycloserine (DCS) and inositol in chronic PTSD (Heresco-Levy et al., 2002; Kaplan et al., 1996).
Special Considerations in Pharmacotherapy for PTSD
There are two issues that merit consideration when prescribing phar-macotherapy for PTSD: polypharmacy, the use of multiple drugs for PTSD symptoms; and maintenance of drug therapy and its implications for relapse. Both of these concerns are discussed in this section.
Polypharmacy
Treatment for PTSD can be complicated, and there is a place for various classes of drug treatment beyond antidepressants (Pfeiffer et al., 2011), sometimes involving drug combinations, including those for which high-grade evidence is lacking. Polypharmacy for PTSD is addressed by Davidson et al. (2005a) as part of the IPAP.
Studies of the VA National Registry for Depression and the VA Drug Benefit Management System cast light on the issues of polypharmacy and off-label drug use for PTSD. In a survey of the VA National Registry in 2001, Valenstein et al. (2004) reported that benzodiazepines were prescribed to 36% of patients, mostly on a long-term basis. Of those who had PTSD, 43% received a benzodiazepine. In the overall sample of depressives, 41% had two psychiatric diagnoses, and 46% had three or more.
In a large national sample of veterans who had PTSD, VA drug benefit data from October 2003 to September 2004 showed that psychotropic drugs were prescribed for 80% of the patients. Of those receiving psy-chotropic drugs, 89% received an antidepressant, 61% an anxiolytic or hypnotic, and 34% a first-generation or second-generation antipsychotic (Mohamed and Rosenheck, 2008). Rates of comorbidity were high and encompassed a wide array of other disorders, including those for which the different drug groups were indicated (for example, an antipsychotic for bipolar disorder). However, off-label prescribing was also common.
From these studies, it is clear that the majority of veterans who have PTSD and receive care at the VA are being prescribed more than one psychotropic drug, including about 80% of them being given an SSRI an-tidepressant. Other drugs are used extensively, some of which may be appropriate for the diagnosis or targeted at particular symptoms. Thus, there is a clear place for rational and carefully conducted polypharmacy, but risks need to be minimized and case records should explain the basis of such practices. Those injunctions apply not only to combining psychotropics, but also to the use of psychotropics with medicines from other categories that have a potential for adverse drug interactions. Given that some drugs carry the potential for abuse or are not known to be effective for PTSD when given alone (such as benzodiazepines, narcotics, and some hypnotics), there needs to be justification for their use and adequate monitoring.
Maintenance Treatment and Risk of Relapse
Given the chronicity of both full and partial PTSD (see Chapter 2) many OEF and OIF veterans will require long-term treatment to ameliorate their symptoms. There have been five trials of long-term maintenance or relapse prevention in people who responded to short-term treatment with anti-depressants or anticonvulsants in PTSD. Two placebo-controlled relapse-prevention studies found that fluoxetine maintenance led to a lower chance of relapse than placebo over 1 year (Davidson et al., 2005b; Martenyi et al., 2002a), and similar findings were reported for sertraline over a longer period (Davidson et al., 2001). No maintenance benefit was obtained with tiagabine over placebo (Connor et al., 2006), and a large relapse-prevention trial of paroxetine versus placebo failed to show differences—both groups had an unusually low rate of relapse over 1 year—and called into question the nature of the original sample (NCCMH and NICE, 2005). Ipser and Stein (2011) noted although there are a number of studies supporting the use of SSRIs and the SNRI venlafaxine for the treatment of PTSD, less is known about how long patients should be treated and the optimal treatment duration to prevent relapse. The relapse rate for PTSD once medication is discontinued is about 40% to 50% and for those who continue on medication, about 15% to 20%, although most studies do not follow outcomes for more than about 15 months.
Although there is debate about antidepressants as a treatment for PTSD (for example, see IOM [2008], NICE, and Australian guidelines), a Cochrane review (Stein et al., 2006) found that response rates in 13 studies were greater for drug than for placebo (the number needed to treat was 4.85, 95% CI 3.85–6.25; n = 1272). The review found that medication was superior to placebo in reducing the severity of PTSD symptom clusters, comorbid depression, and disability, but that it was less well tolerated than placebo. The authors concluded that their results support recommending SSRIs as first-line pharmacotherapy for PTSD for short-term and long-term treatment. A follow-up report by the same group has updated the findings to some extent (Ipser and Stein, 2011) and contains some useful recommendations, including reference to the treatment needs of refractory patients, for whom augmentation or combination approaches may be required. They stated studies of the addition of antipsychotics to ongoing treatment with SSRIs for refractory PTSD “appear to support the efficacy of this strategy, at least with respect to combat-related traumas.” It concluded that war trauma, dose of drug, and sex were not as important in determining the effect of drug treatment as were the size of the study sample and the duration of PTSD.
COMBINED PSYCHOTHERAPY AND PHARMACOTHERAPY APPROACHES
There are two primary strategies for combining pharmacotherapy and psychotherapy for PTSD (Rothbaum, 2008). The additive model combines two effective interventions on the assumption that the benefits would be cumulative. Although some studies suggest there is no advantage in combining traditional psychiatric medications with CBT for any other anxiety disorder (Foa et al., 2002; Gerardi et al., 2009), other studies indicate positive outcomes (Barlow et al., 2000; Blanco et al., 2010).
DCS is an n-methyl-d-aspartate (NMDA) partial agonist that has been found to facilitate the extinction of fear (Davis et al., 2006). It is used in a direct attempt at chemical stimulation of the NMDA-glutamate synapses— thought to be the critical nerve-cell mechanisms that support short-term learning and memory (Bear, 1996; Newcomer and Krystal, 2001)—at the same moment that exposure therapy is helping the patient to learn new behaviors (Davis et al., 2006). DCS alone has no beneficial effect on PTSD (Heresco-Levy et al., 2002); however, combination strategies that involve acute administration of DCS during exposure therapy are being studied (for example, Ressler et al., 2004). In such trials, the medication is expected not to be as effective as the monotherapy but to have an augmenting or facilitating effect in the psychotherapy.
Only one study used both medication and psychotherapy from the outset for the treatment of PTSD (Schneier et al., 2012). The researchers found benefits with combined therapy of 10 weeks of paroxetine and prolonged imaginal exposure in adult survivors of the World Trade Center attacks of September 11, 2001, compared with PE and placebo. However, the benefits of combined therapy at 10 weeks disappeared after an additional 12 weeks of follow-up medication, that is response rates at 22 weeks were similar to placebo. The data are insufficient to determine whether there are additive or interactive effects (or both) of simultaneously administered pharmaco-therapy and psychotherapy for PTSD.
In the first published RCT of combined treatment for PTSD, male and female civilian outpatients who had PTSD were treated with open-label sertraline (up to 200 mg) and then were randomly assigned to receive continuation with sertraline alone or augmentation with PE (Rothbaum et al., 2006). Overall, the additional 5 weeks of sertraline alone was not associated with further improvement on measures of PTSD severity, depression, or general anxiety. However, among partial responders to medication in the first phase, augmentation with PE was associated with further reduction in PTSD severity only (Choi, 2010). In a combination trial that mirrored the Rothbaum et al. (2006) study design, participants first received eight sessions of PE over 4–6 weeks and then were randomly assigned to receive five additional sessions of PE plus either controlled-release paroxetine or placebo (Simon et al., 2008). PE was associated with the largest reductions in PTSD symptoms, and there were no significant differences between placebo and paroxetine in the augmentation phase. Thus, in those two trials, PE enhanced the medication effects in weak medication responders, but medication did not appear to add to the PE effects. In a pilot study of 10 female Cambodian refugees randomly assigned to treatment with open-label sertraline alone or the combination of open-label sertraline and 10 sessions of group CBT, medium to large effect sizes were reported in the combined group (Otto et al., 2003).
INTEGRATIVE COLLABORATIVE CARE
Three large-scale randomized effectiveness trials have successfully used collaborative care models to target and reduce PTSD symptoms in civilian patients presenting at primary care and acute care medical settings (Craske et al., 2011; Zatzick et al., 2004, 2012). Collaborative care is a disease-management model that integrates general medical providers and mental health providers in the treatment of patients who have PTSD and comorbid medical conditions. Collaborative care combines care management with evidence-based psychotherapy (for example, CBT) or pharmacotherapy targeting PTSD. A large series of randomized trials have established the effectiveness of collaborative care that integrates care management, evidence-based pharmacotherapy, and CBT in the treatment of primary care patients who have depression (Bower et al., 2006; Bruce et al., 2004; Dobscha et al., 2009; Gilbody et al., 2006; Katon et al., 1999, 2001, 2010; Kroenke et al., 2009; Miranda et al., 2003; Unutzer et al., 2002; Von Korff, 2004; Wells et al., 2000). However, collaborative care for PTSD has received much less investigative attention. Collaborative care may be useful for the integration of psychotherapy and pharmacotherapy targeting PTSD in nonspecialty mental health settings such as primary care (see also Chapters 6, 8, and 9). Collaborative care may be particularly useful in the integration of new treatment delivery technologies that dismantle or combine elements of established evidence-based practices (Geiss Trusz et al., 2011).
EMERGING THERAPIES FOR PTSD
In this section, the committee considers PTSD treatments that are being used for individuals who have PTSD or for couples and families that have a member who has PTSD. Although a number of studies are being conducted by the DoD, VA, and private researchers on these treatments (see Chapter 4), particularly alternative treatments such as yoga, tai chi, and thought field therapy, to date there is not a substantial evidence base by which to judge their efficacy. It may be difficult to distinguish between alternative treatments that may prove to be efficacious in future studies and those that will not, that is to “differentiate snake oil from penicillin” (Peterson et al., 2011). The committee has heard from numerous service members that such treatments as yoga are helping them, so it is appropriate to discuss these treatments in this report. Furthermore, the committee was specifically asked by Congress to examine these often innovative treatments. The committee expects phase 2 will include more studies on which to base a discussion of the efficacy of these treatments, particularly CAM treatments.
Couple and Family Therapy
Couple Therapy
Cognitive-behavioral conjoint therapy (CBCT) is one couple-based treatment model that focuses on treatment for PTSD and has some evidence to support its efficacy although other couple-based therapy models are undergoing different levels of systematic empirical review.
CBCT for PTSD is a manualized couple-based treatment that has three stages: psychoeducation and safety-building; confronting avoidance, enhancing relationship satisfaction, and improving communication; and cognitive interventions addressing relationship problems and symptoms of PTSD, focusing on maladaptive thoughts around the trauma (Monson et al., 2004, 2008).
In an open trial of CBCT, Monson et al. (2004) treated seven pairs of male Vietnam veterans and their spouses. After treatment, patients experienced significant improvement in PTSD scores based on clinician and spouse ratings but not patient ratings. Spouses expressed slightly improved relationship satisfaction, and veterans reported improvements in depression and anxiety. In another uncontrolled trial, seven couples participated in an uncontrolled trial of CBCT for PTSD (Monson et al., 2011). Among the six couples who completed the treatment, five of the patients no longer met the criteria for PTSD, and there were across-treatment effect-size improvements in patients’ total PTSD symptoms according to independent clinician assessment and reports from the patients and partners. Three of the four couples who had distressed relationships before treatment expressed satisfaction in their relationships after treatment. Patients reported nonsignificant moderate to large improvements in relationship satisfaction and nonsignificant improvements in depression and associated symptoms of anger; however, their partners reported statistically significant, large effect-size improvements in relationship satisfaction. Although there are findings related to moderation of PTSD symptoms, improvements in relationship satisfaction proved to be uneven. Limitations of this study include the small sample size and the absence of a control sample (Monson et al., 2011).
One RCT examined marital adjustment of Middle East combat veterans who had been diagnosed with PTSD (Ahamdy et al., 2009). Impaired marital adjustment and chronic marital distress are considered among the most common manifestations of PTSD. The researchers randomized 60 PTSD veterans who had low degrees of marital adjustment into intervention and control groups. Both groups were evaluated with the ENRICH scale for marital adjustment before and after intervention. The research team concluded that marital adjustment is high in veterans who have PTSD (43%) after the intervention and that the efficacy of CBCT was significant in both the veterans and their spouses.
Although additional couple-therapy approaches are being used with service members, veterans, and their families, data on their efficacy are lacking.
Family Therapy
Sherman et al. (2005) studied access to and use of family and individual treatment for female partners of Vietnam veterans with combat-related PTSD. Of the 89 women surveyed, 64% said access to individual therapy to help with coping was very important and 78% said involvement in family therapy was important for the veteran and his partner, but only 28% of the women had received mental health care in the past 6 months.
The Reaching Out to Educate and Assist Caring, Healthy Families (REACH) program at the Oklahoma City VA Medical Center is a 9-month psychoeducation program for families of veterans with PTSD (Sherman et al., 2009). As assessment of 294 veterans with PTSD who had a family member willing to meet the REACH staff for motivational interviewing sessions, found that 50% of the veterans (and a family member) were willing to learn about the psychoeducation model in spite of the need to overcome such barriers as a more than 15-minute time commitment, the need to relate to a new therapist, and fear of stigma.
Khaylis et al. (2011) conducted a study that used an anonymous self-reported questionnaire aimed at assessing PTSD symptoms, relationship issues, and treatment preference, including interest in family-focused interventions using a sample of 100 National Guard soldiers recently returned from Iraq. A majority of married or partnered soldiers expressed concerns about getting along with their partners and about child-rearing capacities. PTSD symptoms were significantly associated with the degree of relationship concerns. Finally, soldiers revealed a surprising preference for family-based interventions over individual treatment and attached higher importance to family-based interventions tailored to address mental health problems and co-occurring family problems.
Complementary and Alternative Medicine
In response to the committee’s charge to look at CAM therapies for PTSD, it conducted an extensive literature search to identify open-label and RCTs of CAM (also called complementary and integrative medicine) in subjects who had PTSD-related conditions. The evidence base for the use of the therapies for PTSD management is summarized below. The committee will consider CAM treatments for PTSD in greater detail in phase 2 of this study. Many of the studies included in this section were small and case studies or anecdotal reports, but the committee has included them in this report because they illustrate the wide variety of approaches that are being used. The CAM therapies discussed below are not exhaustive. Many CAM approaches are being used by people with PTSD as reported in the popular press, but these approaches are not necessarily being formally studied to assess their efficacy.
As noted in Chapter 4, the use of CAM by military personnel ranges from about 37% (Smith et al., 2007) to about 72% (McPherson and Schwenka, 2004). To examine this widespread use of CAM, the VA, as part of its evidence-based synthesis program, looked at the efficacy of CAM therapies for PTSD (Strauss et al., 2011). Three types of CAM were considered: mind–body techniques such as acupuncture, yoga, and meditation; manipulative and body-base techniques such as spinal manipulation and massage; and movement-based or energy therapies. The VA found that there was insufficient evidence to support the use of meditation versus active treatment, relaxation versus control or active treatment, massage versus control, and movement-based and energy therapies versus control. There was also insufficient evidence to support the use of meditation versus usual care or acupuncture versus group CBT, but there was moderate evidence for acupuncture versus control, based on one RCT.
Yoga
Yoga is a type of mind–body therapy that aims to improve control over the body and mind through the practice of physical positions, breathing, and meditation (Strauss et al., 2011). Iyengar yoga, which uses props to achieve proper body alignment (Shapiro et al., 2007), has been reviewed by Brown and Gerbarg (2005) in which they cite three studies of this form of yoga. In one study, eight Vietnam veterans who had PTSD received 6 weeks of Iyengar yoga instruction; depression, but not anger or insomnia, improved. In a second study of Vietnam veterans, the Iyengar yoga poses for anxiety failed to benefit eight veterans and were discontinued. A third study of eight patients assessed a complex of different approaches and found that breathing techniques, such as Ham Su, provided greater benefit in many core PTSD symptoms.
Sudarshan Kriya yoga (SKY) combines elements of CBT and psychoed-ucation, so it is hard to determine the relative contributions of conventional PTSD therapies and yoga therapy. Brown and Gerbarg (2009) described further work with yoga in PTSD, citing (with few details) open and uncontrolled trials in survivors of Hurricane Katrina, in Australian Vietnam veterans, and in patients who had PTSD associated with sexual abuse. Descilo et al. (2010) obtained beneficial results with SKY in a nonrandomized controlled trial with 183 survivors of the 2004 Asian tsunami; SKY alone and SKY followed by 3–8 hours of exposure therapy were both more effective than a 6-week WL. In a WL-controlled study of 30 Australian veterans, SKY significantly improved PTSD symptoms (Carter and Byrne, 2006).
A randomized WL-controlled trial of 22 flood survivors showed benefit for Patanjali yoga, which emphasized a set series of stretching, postures, breathing, and relaxation (Telles et al., 2010).
Contemplative Approaches
Transcendental meditation, Vipassana meditation, mantram repetition, mindfulness, and mind–body skills approaches have all been studied. Transcendental meditation showed greater improvement than treatment-as-usual in a nonrandomized trial with veterans who had PTSD (Brooks and Scarano, 1985). Five veterans of OEF and OIF responded to 12 weeks of transcendental meditation in an uncontrolled trial by Rosenthal et al. (2011).
Vipassana meditation, a practice of self-observation, failed to improve PTSD in incarcerated people with comorbid substance use disorder and PTSD (Simpson et al., 2007).
Eight weeks of mindfulness training through meditation-based stress reduction was found to result in small but statistically significant improvement in PTSD at 24 weeks in 21 women who had survived child-abuse trauma (Kimbrough et al., 2010).
An uncontrolled trial of frequent mantram repetition, the chanting of a spiritually significant word or phrase to promote focus, calmness, relaxation, or balance (Strauss et al., 2011), resulted in modest but statistically significant improvement in 62 VA outpatients who had PTSD (Bormann et al., 2005). One RCT that compared mantram repetition with WL in 33 veterans who had PTSD showed a significant advantage for the treatment group (Bormann et al., 2008).
Levine et al. (2005) randomized 181 survivors of breast cancer to receive 12 sessions of a CAM program consisting of meditation, imagery, yoga, and a support group with lectures on health, or a standard supportive treatment of weekly psychoeducation. The authors concluded that standard treatment was preferable to CAM on the grounds of cost in that CAM required the services of several professionals.
In an uncontrolled observational study of 25 community-clinic psychiatric patients who received individualized CAM programs for trauma symptoms (massage, acupuncture, Reiki, or Healing Touch), Collinge et al. (2005) noted a mean improvement of 8.6 on a 10-point self-rating scale.
Acupuncture
Acupuncture seeks to improve health and wellness by stimulating the body and mind with the insertion and manipulation of needles placed in particular anatomic points. Hollifield et al. (2007) conducted a three-arm 12-week RCT of acupuncture, CBT, and WL control in civilian patients, most of whom had PTSD stemming from trauma experienced in childhood or adolescence. Both acupuncture and CBT outperformed WL in reducing PTSD. Zhang et al. (2011) conducted a 1-week trial of CBT alone versus CBT plus acupoint electrostimulation in earthquake survivors. Both treatments produced improvement, but the combined CBT–acupuncture group performed significantly better.
Emotional Freedom Technique and Thought Field Therapy
The emotional freedom technique (EFT) uses manual stimulation of acupuncture energy points combined with the patient’s focusing on the traumatic event (Karatzias et al., 2011). In a small pilot study with nine veterans who had combat trauma, 5 days of EFT sessions resulted in lower scores on the PTSD Checklist–Military version immediately after treatment as well as 30 and 90 days after treatment (Church, 2010). A small randomized study with 46 civilians who had PTSD compared EFT with EMDR. Both treatments were effective in lowering CAPS scores immediately after treatment, but at a 90-day follow-up, EMDR resulted in more substantial clinical improvement (Karatzias et al., 2011).
Thought field therapy is a tapping sequence that has been used to treat a variety of mental health problems including phobias, anxiety, trauma, depression, fatigue, attention deficit hyperactivity disorder, learning difficulties, compulsions, obsessions, eating disorders, anger, and physical pain (Callahan 2001a, b). However, there are no empirical studies to support its effectiveness.
Neurofeedback
Neurofeedback—also known as neurotherapy, neurobiofeedback, and EEG biofeedback—uses electroencephalography or functional magnetic resonance imaging to monitor brain activity and the state of a person’s physiological functioning (Othmer and Othmer, 2009). The technique combines systematic desensitization, temperature biofeedback, guided imagery, constructed visualizations, rhythmic breathing, and autogenic training incorporating alpha-theta (3–7 Hz) brainwave neurofeedback therapy. One study conducted in 20 Vietnam combat veterans who had PTSD and comor-bid alcohol abuse found significant improvement after treatment that was maintained at 30 months (Peniston, 1998; Peniston and Kulkosky, 1991).
Qigong and T’ai Chi
Qigong and t’ai chi are traditional Chinese practices that encourage gentle movement of the body to achieve better focus and improved flow of bodily energy (Strauss et al., 2011). Grodin et al. (2008) described four subjects who had PTSD and who benefited from 15 minutes of qigong and t’ai chi before and after 1-hour psychotherapy sessions.
Herbal and Dietary Supplements
Shams et al. (2007) described positive results with the addition of 200 mg of Ginkgo biloba in subjects who had PTSD from an earthquake and who had partially responded to conventional drug therapy. Southwick et al. (1999) reported on four people who had PTSD and experienced worsening panic and anxiety from yohimbine. There have been no PTSD studies of the widely used herbs St. John’s wort and kava, which have been studied extensively in anxiety and depression (Sarris and Kavanagh, 2009).
Two preliminary reports of fish oil did not suggest any benefit in PTSD (Kaplan et al., 2005; Matsuoka et al., 2010), but this treatment has not been adequately studied.
Homeopathy
Homeopathy seeks to treat disease by stimulating the body with serial dilutions of substances that cause similar symptoms of particular disease in healthy people (National Center for Complementary and Alternative Medicine, 2010). Three brief case reports of patients who had PTSD symptoms after sexual trauma and responded to homeopathy were identified (Coll, 2002; Katz, 1996; Morrison and National Center for Homeopathy, 1993). There is no other literature on homeopathy for PTSD.
Art Therapy
Art therapy encourages creative expression as an outlet for emotional processing and expression to facilitate psychologic health. Avrahami (2005) described two cases of veterans with combat PTSD that responded to visual-art therapy. The DoD National Intrepid Center of Excellence at Walter Reed National Military Medical Center has developed the Healing Arts Program, which seeks to treat psychologic health issues through creative avenues including art therapy (Cronk, 2012).
Animal-Assisted Therapy
The use of animals for therapeutic purposes for patients suffering from chronic or acute illness has been documented since the 1800s (Velde et al., 2005). In 1986, the U.S. Army surgeon general appointed a human–animal bond adviser, who has implemented numerous animal-assisted activities and animal-assisted therapy in the DoD. Only animal-assisted therapy specifies the animal as a crucial part of the therapy aimed at improving patient function and has been well documented and evaluated. Animal-assisted therapy programs are run through volunteer organizations or through the support of Vet Centers and are available in diverse locations. Therapy dogs are used in combat and operational stress control activities and also as service animals for wounded service members and veterans. Several organizations, including the Walter Reed Army Medical Center Warrior Transition Battalion, encourage returned service members to train dogs as service animals for other veterans. The presence of a service animal encourages socialization and comforts the patient, disrupting the emotional numbing, hyperarousal, and avoidance that are common symptoms of PTSD, but there are also benefits to the trainer, including learning new skills, developing an emotional bond with the animal, and fulfilling the “warrior ethos” of helping fellow service members who are in need (Ritchie, 2011).
Other animals have also been used for psychotherapy. Horses have been used for animal-assisted activities and animal-assisted therapy, and there is growing evidence of their effectiveness as adjuvants to mental health care in equine-facilitated or equine-assisted psychotherapy. However, very few papers have reviewed equine-facilitated or equine-assisted psychotherapy in the treatment of PTSD, and no RCTs have evaluated its use (Cantin and Marshall-Lucette, 2011; Lentini and Knox, 2009). Dolphins have also been used in animal-facilitated therapy to treat depression and anxiety, but not PTSD specifically. Antonioli and Reveley (2005) conducted an RCT comparing animal-facilitated therapy with dolphins (education, interaction, and care of the dolphins) with an outdoor nature program control group. The dolphin care program resulted in significantly higher decreases in the Beck depression inventory and the Hamilton rating scale for depression than the control program.
Other Somatic Treatments
Electroconvulsive Therapy
Electroconvulsive therapy uses electricity to induce seizures in the brain of an anesthetized patient (Rudorfer et al., 2003). Two reports in the VA/ DoD guideline suggest its benefit in PTSD. One open-label outpatient trial of 20 patients who had treatment-refractory PTSD found that a course of six bilateral treatments achieved a 40% reduction in PTSD symptom severity that was maintained at 6-month follow-up (Margoob et al., 2010). A retrospective chart review found that 12 patients who had PTSD and depression responded partially, that is, depressive but not PTSD symptoms improved after electroconvulsive therapy (Watts, 2007).
Repetitive Transcranial Magnetic Stimulation (rTMS)
In repetitive transcranial magnetic stimulation (rTMS), electromagnets are used to induce cortical neurons in the brain to fire (Cohen et al., 2004). Four studies have assessed rTMS in patients who had PTSD. Three were RCTs, but they used rTMS at different doses, varied laterality (left or right sides of the brain), and varied numbers of treatment applications. Also, few of the subjects were veterans.
In the first RCT, a three-group, 30-patient, double-blind, sham-controlled trial, right- and left-sided 20-Hz rTMS applied to the dorsolat-eral prefrontal cortex both outperformed the control immediately and at a 3-month follow-up, and right-sided TMS was significantly better than left-sided TMS. Further, it was not associated with worsening of cognitive function (Boggio et al., 2010). In another RCT, Cohen et al. (2004) administered 10-Hz rTMS and found significantly greater benefit than control in re-experiencing and avoidance symptoms. Such et al. (2009) administered either 5-Hz rTMS or placebo in a randomized crossover design in which rTMS was given in combination with exposure therapy and antidepressants to nine patients. In this small and underpowered sample, rTMS showed improvement only in hyperarousal symptoms. In an open-label and noncontrolled trial, Rosenberg et al. (2002) reported a benefit of rTMS only for depression in 12 patients who also had PTSD.
On the basis of those findings, the VA/DoD guideline concludes there is sufficient evidence to recommend use of rTMS in treatment for PTSD. It is not known which frequency produces the best response, whether the laterality of treatment (right or left) is important, and what the optimal number of treatments is.
Vagal Nerve Stimulation
There is a single report on vagal nerve stimulation, whereby the brain-stem is stimulated through electric current applied to the vagus nerve in the neck (George and Aston-Jones, 2010). Vagal nerve stimulation was given as open-label treatment to two patients that were treatment resistant (George et al., 2008). Four years after implantation, one of the patients was still receiving vagal nerve stimulation and had sustained improvement compared with baseline. Although there was some evidence of acute and long-term improvement in these patients, no recommendation can be made regarding vagal nerve stimulation for PTSD.
Hyperbaric Oxygen
A preliminary study of low-pressure hyperbaric oxygen therapy (HBOT) was conducted in 16 veterans who had chronic blast-induced mild to moderate traumatic brain injury and PTSD. HBOT is administered in a total-body chamber in which the patient breathes pure oxygen at greater than atmospheric pressure, encouraging the dissolution of oxygen in the body’s fluids and tissues to aid healing (Harch et al., 2007). Results indicated that 40 therapy sessions in 1 month were safe and that there were significant improvements in both postconcussive syndrome and PTSD symptoms (Harch et al., 2012). Those findings, however, must be viewed within the context of the history of HBOT in the treatment of other central nervous system conditions.
Over the past 40 years, small clinical series and individual practitioner experiences have variously led to claims that HBOT was beneficial in the treatment of stroke, dementia, anoxic encephalopathy, multiple sclerosis, and other conditions (for example, Barnes et al., 1987). However, clinical trials have failed to substantiate the claims (for example, Kindwall et al., 1991). Conversely, substantial evidence documents the benefit of HBOT in the delayed treatment of central nervous system decompression sickness (Kizer, 1982). Notwithstanding the challenges in conducting controlled clinical trials of HBOT, such studies will be essential for determining whether this treatment is effective for PTSD.
Conclusions Regarding Other Somatic Treatments
The VA/DoD guideline indicates that electroconvulsive therapy may be considered as an alternative in chronic, severe, medication- and psychotherapy-resistant PTSD—level of evidence II-3 and II-2, fair quality of evidence, and strength of recommendation B. The level of evidence supporting the use of rTMS varies between I and III—generally fair or good quality of evidence and the strength of recommendation B.
GUIDELINES FOR TREATMENT OF PTSD
A number of treatment guidelines for PTSD have been published, some aiming at informing clinicians in general in a given country (such as the United States, the United Kingdom, or Australia), others aiming to inform practice in a specific health system (such as the VA and DoD). This section reviews guidelines issued by the VA and the DoD, the APA, the UK NICE, the Australian National Health and Medical Research Council (NHMRC), and the ISTSS. Table 7-1 (at the end of this section) provides a visual comparison of treatment recommendations of those guidelines with their levels of evidence or rating systems. A summary of the rating systems used by various organizations for PTSD treatment may be found in the review by Forbes et al. (2010). The committee did not evaluate the rating system or evidence base for each guideline. At the very least, the committee believes mental health care providers in the DoD and the VA should adhere to their own guideline for the management of PTSD in service members and veterans, respectively.
TABLE 7-1
Treatment Guideline Categorizations for PTSD.
VA/DoD Clinical Practice Guideline for Management of Post-Traumatic Stress
This guideline, issued in 2010, constitutes an update of the 2004 guideline (VA and DoD, 2004, 2010). The VA Office of Quality Performance and the Office of Patient Care Services and the DoD Army Medical Command selected clinical leaders in primary care, psychiatry, psychology, internal medicine, pharmacology, nursing, and social work to be members of the working group that developed the guideline. The working group supervised a literature review of all PTSD treatment studies from January 2002 to August 2009 and used the results of the review and the ISTSS and APA guideline to come up with the 2010 guideline.
A five-point rating system—A, B, C, D, and I—was used to indicate the strength of recommendations; the ratings were based on the literature review and on expert consensus. A was the highest rating and indicated there was good evidence that the intervention in question improved outcomes. A rating of B indicated a fair amount of evidence supported the use of the intervention in question. A rating of C indicated that the working group did not make a recommendation for or against the routine use of the intervention inasmuch as the benefit–risk ratio was too close to make a general recommendation. A rating of D indicated the presence of evidence that either the intervention was harmful or the risks outweighed the benefits offered by it. Finally, I indicated evidence was lacking, of insufficient quality, or conflicting; therefore, a recommendation could not be made for or against providing the treatment routinely. The working group also included a set of algorithms oriented to the initial point of contact being a primary care or a mental health setting in a VA or DoD context.
The working group recommended that initial treatment include both psychotherapy and pharmacotherapy. It also cautioned against the use of psychologic debriefing immediately after a traumatic event.
The guideline recommends evidence-based psychotherapeutic interventions for PTSD that are most strongly supported by RCTs: those interventions are broadly categorized as trauma-focused psychotherapy or stress inoculation training (VA and DoD, 2010). Trauma-focused psychotherapies commonly involve exposure or cognitive restructuring (for example, PE, CPT, and EMDR), and they may be combined with anxiety management, stress reduction skills, and psychoeducation. The guideline states that other CBT interventions that are not trauma focused are less effective. The working group noted that therapy provided in clinical trial settings differs from therapy practiced in day-to-day care, and the recommendations in the guideline represent the techniques and protocols as reported in the RCTs.
Although benzodiazepines have historically been used as effective treatments for anxiety and insomnia, the guideline recommends against their use as preventive measures “due to lack of evidence for effectiveness and risks that may outweigh potential benefits.” Studies with propranolol have had mixed results, and overall the VA/DoD guideline concluded that despite some positive results, “the size and weak study designs of the investigations do not allow for definitive conclusions regarding the value of these medications in preventing the development of PTSD symptoms after traumatic events.”
The VA/DoD 2010 guideline states that “there is insufficient evidence to draw concrete conclusions or make specific recommendations regarding the use of pharmacological agents for prevention of PTSD.” The guideline further concludes that there is insufficient evidence to recommend the use of CAM approaches as a first-line treatment for PTSD; however, it states that CAM approaches may be considered as adjunctive treatments for specific symptoms of PTSD such as relaxation techniques (for example, yoga and massage) for hyperarousal and for comorbid conditions, such as using acupuncture for the management of chronic pain.
The committee notes that new policy guidance on assessment and treatment of PTSD issued by the U.S. Army (2012) on the use of atypical antipsychotics and benzodiazepines requires that health care providers who prescribe these drugs must clearly document their rationale for using them in the patient’s medical record and must obtain informed consent from the patient. The guidance also states that clinicians should use the 2010 VA/ DoD guideline when treating patients with symptoms of traumatic stress.
American Psychiatric Association Guideline
The APA published Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder in October 2004 and followed it with a Guideline Watch in March 2009, which updated the research review of PTSD treatments. The guideline was developed by a work group that consisted primarily of psychiatrists. In a review of the different PTSD guidelines, Forbes et al. (2010) noted that although the group developed evidence tables that summarized studies, it did not present clear concluding statements for each of the treatments that it assessed.
The work group used a three-point coding system—I, II, and III—to identify treatments. I indicated a recommendation with substantial clinical confidence; II, with moderate clinical confidence; and III, on the basis of individual circumstances. The ratings were based on a review of the treatment literature and expert consensus.
The APA guideline and the Guideline Watch recommend three potential treatment approaches for PTSD, either alone or in combination: education and support, psychotherapy, and pharmacotherapy. The guideline states that “the therapist should first exhaust the treatments for which there is the best evidence of efficacy before trying more novel treatments.” Furthermore, the response to treatment may be affected by trauma type and timing of the treatment after the traumatic event.
The guideline recommends CBT as an effective treatment for core symptoms of acute and chronic PTSD. Other recommended psychother-apies include EMDR, stress inoculation, imagery rehearsal, and PE for treatment of PTSD and PTSD-associated symptoms such as anxiety and avoidance. The guideline notes that all of these treatments share an element of controlled exposure and that this may be the critical intervention.
The APA guideline (APA, 2004; Benedek et al., 2009) recommend SSRI and SNRI antidepressants as the drugs of first choice on the grounds that they reduce all core symptom clusters of PTSD and important associated symptoms (such as suicidality, impulsivity, and aggression) and several common comorbid disorders (such as panic and depression). The guideline mentions, however, a series of five negative SSRI–SNRI trials in U.S. samples of combat veterans. Only one small study of nefazodone proved positive. The tricyclic drugs imipramine and amitryptline and the MAOI phenelzine are recommended as backup approaches, but these drugs have greater toxicity. The three positive trials of these drugs were all carried out in U.S. World War II and Vietnam veterans who had combat-related PTSD, and this suggests a possible role for the older antidepressants in nonresponders.
UK National Institute of Health and Clinical Excellence Guideline
The UK NICE guideline for PTSD was developed by the National Collaborating Center for Mental Health and issued in 2005 (NECMH and NICE, 2005). The guideline development group was focused on informing policy and practice primarily through evidence-based recommendations, and thus, considered treatments that had demonstrated efficacy. The group first developed a scope document that set out specific criteria for the guideline (such as population to be focused on and types of treatments to review), so the final guideline would be applicable to the British National Health System as a whole and cover generally available therapies. A set of research questions was developed (for example, “For adults with PTSD, does any psychological intervention confer any advantage over other psychological interventions?”) to determine the current state of evidence supporting specific PTSD interventions. Using the questions as guidance, a group separate from the guideline development group reviewed RCTs and conducted formal meta-analyses. Effect sizes for clinical effectiveness were determined, as were relative risk ratios to represent clinically significant differences. The guideline development group then used that information to produce evidence statements.
The guideline development group established a four-point rating system—A, B, C, and GPP—that was based on the level of empirical support available for a given treatment. An A rating indicated the intervention was supported by a consistent body of evidence, including at least one RCT. A B rating indicated the treatment was supported by well-conducted clinical trials but that no RCTs had tested the intervention. A C rating indicated the treatment was supported by expert committee reports or opinion but that good clinical studies were absent. Finally, a GPP (good practice point) rating indicated the treatment was considered good practice by the guideline development group.
The guideline development group also recommended that a trauma-focused psychotherapeutic intervention be considered initially, not phar-macologic interventions. And it recommended against single-session psychotherapy interventions that focus on the trauma in the aftermath of a trauma.
The guideline states that using the criterion for a clinically important effect, the drug treatments were disappointing. Although there are a number of RCTs that met the inclusion criteria, they had relatively small samples and needed to be interpreted with some caution. These RCTs suggest there may be a clinically important effect for mirtazapine, amitriptyline, and the MAOI antidepressants phenelzine and brofaromine. The guideline recommends paroxetine on the basis of robust data although it did not meet the criterion of a clinically significant effect. The guideline is similar to the Australian guideline with respect to recommendations for pharmacotherapy for PTSD and essentially reaches the same conclusions, albeit with some differences in the specific drugs that are recommended.
Australian National Health and Medical Research Council Guidelines
The Australian Guidelines for the Treatment of Adults with Acute Stress Disorder and Posttraumatic Stress Disorder were published by the Australian Centre for Posttraumatic Mental Health (NHMRC, 2007). The guideline development group consisted of trauma experts in Australia who worked in consultation with a multidisciplinary group consisting of professionals who worked with people who had PTSD. In an approach similar to that of the group that developed the NICE guideline, the group started with a series of 18 research questions (for example, “For adults with PTSD, is the combination of individual therapy and group therapy more effective than either alone?”) that an outside group, Adelaide Health Technology Assessment, used as the basis of a systematic review of RCTs. The guideline development group also drew on the reviews conducted by NICE (2005) and by the VA and the DoD (2004). Again, as in the case of the NICE guidelines, formal meta-analyses were conducted, effect sizes for clinical effectiveness were determined, and relative risk ratios were calculated to represent clinically significant differences.
The guideline development group made recommendations based on a five-point scale—A, B, C, D, and GPP—with A indicating that a treatment had the strongest evidence supporting its use and D indicating that a treatment had very weak evidence supporting its use. Treatments deemed to be effective on the basis of expert consensus opinion despite lacking empirical evidence were rated GPP (good practice point). Like the NICE guideline group, the Australian group recommended that a trauma-focused psychotherapeutic intervention be considered the first line of treatment, not pharmacologic interventions. The group also recommended against offering psychologic debriefing and other structured psychosocial interventions in the wake of a traumatic event. Although this guideline favors psychotherapy as the first-line treatment for PTSD, it outlines a number of clinical scenarios in which use of an antidepressant is warranted and indicates a preference for SSRIs in such circumstances.
In interpreting the Australian guideline, it is important to point out that the guideline development committee used idiosyncratic criteria to define remission (which was regarded as synonymous with failing to meet the diagnostic criteria for PTSD) and then failed to include response or remission rates as an outcome even though these have traditionally been key measures in psychopharmacology studies.
International Society for Traumatic Stress Studies Guidelines
A group of PTSD treatment experts developed a set of PTSD treatment guidelines, Effective Treatments for PTSD: Second Edition, for ISTSS, a group of practitioners in different disciplines, which were issued in 2009. The focus of the guidelines was on identifying any evidence available to support the use of numerous psychotherapeutic and psychopharmacologic treatments for PTSD that were currently in use. Different working groups focused on specific intervention categories and developed evidence summaries. Forbes et al. (2010) note that although some working groups included evidence tables, information on the methods used to review the literature, and treatment effect sizes, this was not done uniformly by all the groups.
The working groups used a six-point scale—A, B, C, D, E, and F—to grade the strength of evidence available for each intervention. A grade of A indicated that evidence for a particular treatment was based on RCTs, B indicated evidence was based on well-designed studies without randomization or placebo comparison, C indicated evidence was based on naturalistic clinical studies and clinical observations, D indicated evidence was based on long-standing and widespread clinical practice that had yet to be tested empirically, E indicated evidence was based on long-standing practice by a selected group of clinicians that had not been tested empirically, and F indicated a treatment was new and had not been tested empirically.
Although the authors of the guidelines did not provide recommendations on which treatments should be considered first-line, they did recommend that psychopharmacologic treatment should be considered if CBT were not available or should be used in combination with CBT. Furthermore, the ISTSS guidelines did not recommend psychologic debriefing immediately after a traumatic event.
Summary of Guidelines
There are many similarities among the recommendations of the reviewed guidelines as shown in Table 7-1. All the guidelines strongly support the use of trauma-focused psychologic treatment for PTSD in adults and children with an emphasis on trauma-focused CBT, such as PE and CT. All but one of the guidelines recommended against the use of psychologic debriefing soon after exposure to trauma.
Key differences among the guidelines are the extent to which expert consensus contributed to the strength of the recommendation rating and the kind of the literature reviewed (only RCTs vs. all PTSD-treatment studies). Some guidelines were more stringent in what studies were allowed in their review (NICE and NHMRC examined only RCTs) and gave high recommendations to a small number of treatments (predominantly trauma-focused psychotherapies). Other guidelines (such as ISTSS, APA, and VA/ DoD) were more expansive in their review of the literature and incorporated clinical consensus into their recommendations; this resulted in more (admittedly muted) recommendations for other types of therapy, such as IRT in the case of VA/DoD and APA.
One example of the variation in the guidelines assessment of a specific therapy is EMDR. EMDR was given the highest rating in all but one of the guidelines. The APA guideline was the only one that did not accord EMDR the highest rating, instead giving it a second-tier rating. Forbes et al. (2010) noted that what contributed to that difference was how the absence of support for the use of eye movements in EMDR was addressed. The other guidelines used effect sizes to determine the effectiveness and significance of EMDR, but the APA work group took into account the lack of empirical support for the use of eye movements when determining their recommendations. The NHMRC guidelines stated that EMDR should be considered a first-line treatment only if it included in vivo exposure. Forbes et al. (2010) note that such an approach questions when it is justified to engage in focused analyses and whether it is unfair to subject one type of intervention and not another to such analysis.
Other Organizational Reviews of Pharmacotherapy for PTSD
Institute of Medicine Report
The 2008 IOM report on treatment for PTSD concluded that the evidence was inadequate to determine the efficacy of SSRIs and all other drug categories in PTSD. However, one committee member (the expert in psychopharmacology) dissented from that view and indicated that, in his opinion, the evidence in favor of SSRI monotherapy was suggestive of efficacy in the general population, but not male veterans, with chronic PTSD. For atypical antipsychotics, he believed the evidence was also suggestive of efficacy for this add-on treatment.
The committee further found there was sufficient evidence on the basis of RCTs of the efficacy of exposure therapy to treat PTSD, but that there was inadequate evidence for the efficacy of EMDR, cognitive restructuring, and coping skills training. The committee also concluded there was inadequate evidence on the efficacy of therapy delivered in a group format.
International Psychopharmacology Algorithms
In 2005, an international group of PTSD academicians prepared an evidence-based set of stepwise clinical decisions for PTSD with specific reference to different clinical situations, such as suicidal patients, substance abusers, people who had bipolar disorder, pregnant women, and litigation. It recommended medications and dosing (Connor and Stein, 2005; Davidson et al., 2005a; IPAP, 2005; Stowe and Newport, 2005). The algorithms are unique in addressing whether, when, and how to stop a drug, switch drugs, augment or change a dosage, and manage PTSD in women of childbearing potential.
Other Authorities
The British Association of Psychopharmacology (2005), the World Federation of Societies of Biological Psychiatry (2008), and the Canadian Psychiatric Association (2006) all recommend the choice of an SSRI or SNRI antidepressant as first-line therapy if pharmacotherapy is to be used for chronic PTSD. The drugs are fluoxetine, paroxetine, sertraline, and venlafaxine-extended release.
SUMMARY
There are numerous psychosocial treatments for PTSD, many of which are variants of evidence-based treatments, such as exposure therapy and cognitive therapy. On a whole, the efficacy of these treatments has been limited to pretreatment and posttreatment self-reported assessments, which makes interpretation of the outcomes difficult. The frequent lack of control groups in efficacy studies means that reductions in PTSD symptoms may be due to factors unrelated to the treatment under investigation such as repeated assessment, passage of time, and expectation that being in a treatment is helpful. There are also several effective pharmacotherapies for treating PTSD, particularly SSRIs.
Overall, group-based CBT treatment for individuals diagnosed with PTSD is associated with improvements in symptoms of PTSD, but in general, the outcome is not as good as that found in individual therapy (Schnurr et al., 2003). One study is examining the efficacy of group versus individual CPT in active-duty military personnel, but results are not yet available. Although cognitive behavioral treatments have been studied extensively in the treatment of PTSD, there are still areas that need to be investigated. These areas include how to increase the immediate and long-term efficacy and efficiency of existing treatments; how to deliver effective treatments in fewer sessions; the use of pharmacological agents such as DCS to enhance inhibitory learning during exposure; and the use of other agents such as yohimbine as possible adjuncts to exposure therapies. Researchers are also challenged by the fact that some patients who improved with CBT have shown various degrees of relapse, and this suggests that treatments do not eradicate the trauma memories. Other areas for research include ways to improve the training in and use of recommended PTSD treatments throughout the DoD and the VA.
Currently, there is a lack of empirical evidence that supports CAM approaches to treat for PTSD. The most substantial evidence comes from studies of yoga, contemplative treatments, and acupuncture, but there are still few RCTs. Where the evidence is suggestive, as for yoga and acupuncture, there is considerable debate as to what particular approach is most effective. There is a considerable amount of work being done to find new approaches for delivering evidence-based treatments for PTSD to service members, veterans, and their families, including group and couple therapy and telemental health and Internet-based therapies. If these treatment delivery methods are beneficial, they may be used to reach service members and veterans who might otherwise not have access to mental health care because of location, timing, or other concerns. In Chapter 9 the committee discusses barriers for disseminating effective treatments and possible ways to overcome them.
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- Treatment - Treatment for Posttraumatic Stress Disorder in Military and Veteran ...Treatment - Treatment for Posttraumatic Stress Disorder in Military and Veteran Populations
- LOC110262316 [Sus scrofa]LOC110262316 [Sus scrofa]Gene ID:110262316Gene
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