The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice GuidelineFREE

The CPG suggests screening for PTSD using the Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5; recommendation 1), a 5-item questionnaire that performs well in detecting a DSM-5 PTSD diagnosis (7). The evidence consisted of 2 studies conducted in veterans using VA care (7, 8), including 1 study of more than 400 VA primary care patients (7). Both study samples were predominantly White male veterans. Studies in other populations (for example, women and persons of other genders, active-duty service members, and samples with greater racial or ethnic diversity) are necessary to establish cut point scores appropriate for the population. For example, 1 of the 2 included studies found that the optimal cut point was the same for men and women but performed less well for women (7). No potential harms were identified in the systematic evidence review. Patient values and preferences varied because some patients do not like completing screening measures.

The CPG suggests using a validated, structured, clinician-administered interview, such as the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) (9) or PTSD Symptom Scale Interview for DSM-5 (PSSI-5) (10), to diagnose PTSD (recommendation 2). The recommendation is based on 2 studies demonstrating the diagnostic validity of the CAPS-5 (9, 11) and 1 study of the PSSI-5 (10) (included in the evidence review for the 2017 CPG but not included in the current evidence review or affecting the strength of this recommendation). The latter study found good convergent validity between PSSI-5 and CAPS-5 total scores and moderate correspondence between CAPS-5 and PSSI-5 diagnoses. The benefits of clinician-administered interviews outweighed the potential harms. Although some patients may experience distress when asked to describe traumatic events and associated symptoms, this risk is generally outweighed by the value of an appropriate diagnosis for treatment planning. Patient values and preferences may vary because some patients might find detailed assessments inconvenient or invasive. The Work Group recognized that structured, clinician-administered interviews can be resource-intensive and time-consuming, often require specialized training and competency, and therefore may not be routinely feasible in clinical settings.

For assessing symptom change, the CPG suggests use of validated instruments (recommendation 3), such as the PTSD Checklist for DSM-5 (12) or a structured, clinician-administered interview (for example, CAPS-5) (9), on the basis of 2 studies in veteran samples (13, 14). The evidence is further supported by prior research (included in the evidence review for the 2017 CPG but not affecting the strength of this recommendation) that found correspondence in longitudinal scores in the DSM-IV versions of these 2 instruments (15). Although no studies on sensitivity to change for the PSSI-5 were found in the evidence review, prior research (included in the evidence review for the 2017 CPG but not the current evidence review) supports its validity and applicability for measuring symptom change (10). The benefits of monitoring symptom change outweighed the potential harms. Patient values and preferences may vary because some patients might find assessments inconvenient or invasive whereas others may appreciate the value of systematically tracking progress.

Prevention of PTSD is important because service members and veterans may be exposed not only to combat in a war zone but also to other traumatic events during or after military service. Unfortunately, the evidence was insufficient to make a recommendation for using psychotherapy or pharmacotherapy in the immediate posttrauma period to prevent PTSD in traumatized persons (recommendation 4). Evidence was also insufficient to make a recommendation for using pharmacotherapy to prevent PTSD in persons with ASD (recommendation 6). However, the CPG suggests trauma-focused cognitive behavioral therapy to prevent PTSD in persons with ASD (recommendation 5). No specific protocol was identified, but 1 systematic review (with 9 studies, 4 of which had the critical outcome of clinician-rated PTSD) found that patients with ASD who received brief, trauma-focused cognitive behavioral therapy, including cognitive restructuring and exposure, had reduced PTSD symptom severity at 3- to 6-month follow-up compared with those who received supportive counseling or were on a waitlist (16). The body of evidence had some limitations, including small sample sizes, risk of bias, and lack of studies in service members or veterans. However, the benefits of reduced symptoms and lower rates of subsequent diagnosis of PTSD outweighed the potential harms and burdens (such as time required to attend psychotherapy sessions).

Three psychotherapies (recommendation 8) and 3 pharmacotherapies (recommendation 15) are recommended for treating PTSD. When both treatment methods are available and feasible, the CPG recommends the psychotherapies over the pharmacotherapies (recommendation 7). The Work Group based the recommendation on 2 systematic reviews included in the 2017 version of the CPG (17, 18) and 1 newer systematic review and network meta-analysis (19). The reviews found that trauma-focused psychotherapies impart greater improvement on core PTSD symptoms than pharmacotherapies and that these improvements persist longer. These findings held true even in a meta-analysis of medications and psychotherapies in which the only psychotherapy studies included had used active comparison treatments, such as present-centered therapy (PCT), as opposed to waitlists or usual care (17).

In making this recommendation, the Work Group considered several factors in addition to the apparent differences in the magnitude of change associated with the 2 treatment methods. First, although the risks for adverse effects or negative reactions vary across individual patients, they are generally more likely to occur with pharmacologic treatments than with psychotherapies (recommendation 15 and Appendix B in the full guideline) (4). Second, the positive effects of medication treatment often diminish over time and are lost when medications are withdrawn (17). The body of evidence had some limitations, including few direct comparisons and studies with small sample sizes. The benefits of using psychotherapy over pharmacotherapy slightly outweighed the potential harms, which were considered minimal. Patient values and preferences varied largely, with some patients expressing a strong preference for one method or the other, but most patients seem to prefer psychotherapy over pharmacotherapy, even when psychotherapy is trauma-focused (20–23).

The 2017 CPG for PTSD and ASD recommended trauma-focused therapies that use cognitive, emotional, or behavioral techniques to facilitate processing a traumatic experience and in which the trauma focus is a central component of the therapeutic process. After reviewing the evidence on specific psychotherapies, the 2023 CPG Work Group recommended the following 3 trauma-focused psychotherapies (recommendation 8) on the basis of evidence of efficacy from 6 systematic reviews (24–29): cognitive processing therapy (CPT) with or without a trauma account, eye movement desensitization and reprocessing (EMDR), and prolonged exposure (PE). The body of evidence had some limitations, including no studies of EMDR in active-duty service members and few studies of EMDR in veterans. The benefits of CPT, EMDR, and PE in improving the critical outcome of clinician-rated PTSD symptoms and other important outcomes outweighed the potential harms (such as adverse events), which were small.

In addition to recommending CPT, EMDR, and PE, the CPG suggests Ehlers cognitive therapy (CT), PCT, and written exposure therapy (WET) on the basis of evidence from 2 systematic reviews and 1 individual study (24, 30, 31) (recommendation 9). Regarding patient preferences, PCT might be more acceptable than trauma-focused treatments because it does not require talking about trauma. In addition, PCT has lower dropout rates than trauma-focused treatments (32). The body of evidence had some limitations, including no studies of Ehlers CT and only 1 study of WET in military populations. All studies of CT and WET were done by the respective treatment developers, which might limit generalizability of findings because of potential allegiance bias. No studies compared PCT with an active control, although there were multiple comparisons with active treatment. The benefits of Ehlers CT, PCT, and WET in improving the critical outcome of clinician-rated PTSD symptoms and other important outcomes outweighed the potential harms (for example, of adverse events), which were small.

The Work Group found insufficient evidence to make a recommendation about other psychotherapies (recommendation 10) based on 6 systematic reviews and meta-analyses and 2 randomized controlled trials (RCTs) (24, 33–38), because either there were few studies of a treatment with the critical outcome of clinician-rated PTSD or the efficacy of a treatment was inconsistent across studies. (Recommendations 11 to 14 refer to additional psychotherapies for which evidence was inconsistent.)

The CPG recommends paroxetine, sertraline, and venlafaxine (recommendation 15) on the basis of a systematic review that included 6 trials of paroxetine, 6 trials of sertraline, and 2 trials of venlafaxine (39). This recommendation is a change from the 2017 CPG, which also recommended fluoxetine on the basis of older systematic reviews (17, 40). The more recent review (39) found no benefit of fluoxetine for clinician-rated PTSD in a single trial. Fluoxetine is now categorized as having insufficient evidence for or against its use.

The body of evidence had limitations, including risk of bias and concerns about study quality and high heterogeneity. Generalizability to military populations may be limited because there were only 2 studies in veterans (1 of which was negative) and no studies of service members. However, the Work Group determined that the benefits of treatment with paroxetine, sertraline, and venlafaxine outweighed the small potential harm of adverse events. Patient values and preferences may vary because of differing attitudes about use of medications.

Evidence was rated as insufficient for a large group of medications (recommendation 16), including several changes from the 2017 CPG based on more rigorous application of GRADE criteria and 2 new systematic reviews (39, 41), as well as consideration of the evidence reviewed for the 2017 CPG (17, 40). Most notably, olanzapine and quetiapine (previously weak against) and phenelzine (previously weak for) are now classified as neither for nor against.

The Work Group found that evidence was insufficient to recommend for or against the use of psychedelics (such as psilocybin) for the treatment of PTSD (recommendation 17); the Combination and Augmentation section below discusses 3,4-methylenedioxymethamphetamine (MDMA)–assisted psychotherapy. No studies meeting search criteria were identified, and these agents cannot be legally prescribed in the United States outside a research study. In addition, these agents might have adverse effects, risks, or both that are currently unknown (and adverse events have been anecdotally reported).

Recommendation 18 suggests against divalproex, guanfacine, ketamine, prazosin, risperidone, tiagabine, and vortioxetine for the overall treatment of PTSD on the basis of 3 systematic reviews and 1 RCT (39, 41–43) (see recommendation 32 on prazosin for nightmares). The 2017 CPG recommended against risperidone and neither for nor against vortioxetine. The weak against recommendation for ketamine in the 2017 CPG was maintained in the 2023 version, supported by an additional negative trial (44). The body of evidence had limitations, including a lack of evidence of effectiveness. Thus, the Work Group determined that the benefits of these medications were outweighed by the harms, which include multiple potential side effects and risks associated with increased blood pressure and heart rate. Patient values and preferences are likely to vary because of the different considerations for each medicine, including the level of evidence for an effect on PTSD symptoms, side effect profiles, and potential benefits for alternative uses.

The CPG recommends against benzodiazepines on the basis of a lack of evidence of benefits and the presence of known harms (recommendation 19). A systematic review (39) included a single negative trial that, along with evidence from the 2017 CPG for PTSD and ASD (45), found that benzodiazepines are associated with misuse, decreased effectiveness of recommended PTSD treatments, and adverse cognitive changes, especially in the elderly.

The CPG also recommends against cannabis or cannabis derivatives for the treatment of PTSD (recommendation 20) because of the lack of well-designed RCTs and potentially serious side effects associated with cannabis use in 4 systemic reviews (46–49). Evidence from 1 randomized, double-blind, crossover study that did not meet inclusion criteria for the CPG review because of insufficient length of follow-up (and therefore did not affect the strength of this recommendation) indicated no difference in change in PTSD symptom severity between active cannabis concentrations and placebo (50).

Evidence was insufficient to recommend for or against the combination of evidence-based medications or psychotherapies to enhance treatment outcomes in PTSD (recommendation 21). This largely reflects the scarcity of studies examining combination treatments, but also findings of a systematic review (51) and individual studies (52–56). Similarly, with the exception of atypical antipsychotic medications, evidence (40, 42) was insufficient to support augmenting recommended or suggested psychotherapy or medication treatment with other non–PTSD-indicated medication (recommendation 21). The CPG suggests against atypical antipsychotic medications because of lack of demonstrated benefit and known harms (recommendation 22). Only 3 atypical antipsychotic medications—risperidone, aripiprazole, and olanzapine—have been evaluated for augmenting medication treatment in PTSD (42, 57, 58). For these and other atypical antipsychotic medications for which no studies exist, there are known serious risks, including weight gain, hyperlipidemia, diabetes mellitus, QTc prolongation, and extrapyramidal side effects (59).

The Work Group found insufficient evidence to recommend for or against MDMA-assisted psychotherapy for the treatment of PTSD (recommendation 23). A systematic review of 5 RCTs found benefit for improving clinician-rated PTSD (42), but the evidence had limitations: relatively few total participants (n = 176), few veterans or active-duty service members, and differing control conditions that affected adequacy of blinding. The MDMA-assisted psychotherapy protocol (three 8-hour medication sessions staffed by 2 therapists and 12 weekly 90-minute psychotherapy sessions) would be challenging to implement in current VA and DoD (and other) health care systems.

The Work Group found the evidence insufficient to make a recommendation on a range of somatic treatments, including capnometry-assisted respiratory therapy, hyperbaric oxygen therapy, neurofeedback, NightWare, repetitive transcranial magnetic stimulation, stellate ganglion block, and transcranial direct current stimulation (recommendation 24). For most treatments, evidence was mixed or had methodological limitations. No RCTs studied clinician-rated PTSD severity for NightWare or transcranial direct current stimulation. No new studies were identified to support the efficacy of electroconvulsive therapy or vagus nerve stimulation for the treatment of PTSD, so the Work Group used the assessment of the evidence from the 2017 CPG for PTSD and ASD, a meta-analysis and 2 RCTs (60–62), to make a weak against recommendation (recommendation 25). Given the lack of efficacy data, the potential harms of electroconvulsive therapy and vagus nerve stimulation (such as risks associated with general anesthesia and, for vagus nerve stimulation, surgery) outweighed the potential benefits.

The CPG suggests mindfulness-based stress reduction for treating PTSD (recommendation 26) on the basis of a systematic review including 5 RCTs that used the critical outcome of clinician-rated PTSD (63). Three of these RCTs involved veterans and showed that mindfulness-based stress reduction outperformed present-centered group therapy (64, 65) or usual care (66). Evidence was insufficient to make a recommendation for all other mind–body interventions or alternative practices (recommendations 27 and 28).

Technology, such as mobile apps and video teleconferencing, can increase access to mental health care. The CPG recommends video teleconferencing to deliver the psychotherapies with strong or weak for recommendations that have been validated for telehealth delivery (recommendation 29). Three RCTs reviewed as part of the 2017 CPG for PTSD and ASD (67–69), plus a systematic review and 2 additional RCTs identified in the current evidence review (70–72), suggest that delivery of CPT and PE via video teleconferencing is noninferior to face-to-face delivery. The Work Group determined that the benefits outweighed the potential for harm from lack of treatment if patients cannot receive in-person treatment. However, patient values and preferences vary because some patients might prefer in-person care. Evidence was insufficient to make a recommendation for or against other technological methods, such as mobile apps (recommendations 30 and 31).

In addition to examining the effects of interventions on overall PTSD severity, the Work Group examined the effects on nightmares, a core symptom of PTSD. Although the CPG suggests against using prazosin to treat PTSD symptoms, the evidence supports a weak for recommendation for prazosin to treat nightmares (recommendation 32), as demonstrated by 2 systematic reviews and 1 RCT (73–75). Insufficient evidence exists to recommend for or against imagery rehearsal therapy, exposure relaxation and rescripting therapy, imaging rescripting and reprocessing therapy, or NightWare (recommendation 33).

In recommendation 34, the CPG suggests that the presence of comorbid psychiatric disorders not prevent delivery of the psychotherapies listed in recommendations 8 and 9. Evidence from 5 systematic reviews (36, 76–79) and 11 individual studies (80–90) showed that persons with comorbid conditions, including substance use disorders, can tolerate and benefit from evidence-based individual PTSD treatments, such as PE and CPT. The evidence included both standard treatments of PTSD and integrated treatments that address comorbidity (83). Evidence from 2 systematic reviews (76, 77) and 4 individual studies (85, 86, 88, 89) showed that the presence of comorbid conditions does not alter the effectiveness of these treatments. The evidence indicates that the presence of comorbid conditions should not delay PTSD treatment because, for adults diagnosed with PTSD, treatment safety and effectiveness do not seem to be altered by the presence of comorbid conditions. The body of evidence had limitations, including small sample sizes and high dropout rates, although the benefits of treating PTSD in patients with comorbid conditions outweighed the potential harms. Therefore, the CPG suggests that the presence of co-occurring substance use disorder or other disorders not preclude psychotherapies that received a strong or weak for recommendation.

Providers may consult other VA/DoD guidelines for recommendations on the treatment of comorbid conditions in PTSD. For example, although the 2023 CPG for PTSD and ASD suggests against the use of ketamine for PTSD, the 2022 VA/DoD CPG for major depressive disorder recommends ketamine for treatment-resistant cases (91). Because PTSD is highly comorbid with major depressive disorder in both veterans and service members, ketamine might be considered for treating depression in patients with both conditions.