Impact of PTSD treatment on postconcussive symptoms in veterans: A comparison of sertraline, prolonged exposure, and their combination.

Many Veterans who served in Iraq and Afghanistan struggle with posttraumatic stress disorder (PTSD) and the effects of traumatic brain injuries (TBI). Some people with a history of TBI report a constellation of somatic, cognitive, and emotional complaints that are often referred to as postconcussive symptoms (PCS). Research suggests these symptoms may not be specific to TBI. This study examined the impact of PTSD treatment on PCS in combat Veterans seeking treatment for PTSD. As part of a larger randomized control trial, 198 Operation Iraqi Freedom, Operation Enduring Freedom, Operation New Dawn (OIF/OEF/OND) Veterans with PTSD received Prolonged Exposure Therapy, sertraline, or the combination. Potential deployment related TBI, PCS, PTSD and depression symptoms were assessed throughout treatment. Linear mixed models were used to predict PCS change over time across the full sample and treatment arms, and the association of change in PTSD and depression symptoms on PCS was also examined. Patterns of change for the full sample and the subsample of those who reported a head injury were examined. Results showed that PCS decreased with treatment. There were no significant differences across treatments. No significant differences were found in the pattern of symptom change based on TBI screening status. Shifts in PCS were predicted by change PTSD and depression. Results suggest that PCS reduced with PTSD treatment in this population and are related to shift in depression and PTSD severity, further supporting that reported PCS symptoms may be better understood as non-specific symptoms.

Treatment of posttraumatic stress disorder with prolonged exposure for primary care (PE-PC): Effectiveness and patient and therapist factors related to symptom change and retention.

Prolonged exposure (PE) is a first-line treatment for posttraumatic stress disorder (PTSD) available in specialty mental health. PE for primary care (PE-PC) is a brief version of PE adapted for primary care mental health integration, composed of four-eight, 30-min sessions. Using retrospective data of PE-PC training cases from 155 Veterans Health Administration (VHA) providers in 99 VHA clinics who participated in a 4- to 6-month PE-PC training and consultation program, we examined patients' PTSD and depression severity across sessions via mixed effects multilevel linear modeling. Additionally, hierarchical logistic regression analysis was conducted to assess predictors of treatment dropout. Among 737 veterans, medium-to-large reductions in PTSD (intent-to-treat, Cohen's d = 0.63; completers, Cohen's d = 0.79) and small-to-medium reductions in depression (intent-to-treat, Cohen's d = 0.40; completers, Cohen's d = 0.51) were observed. The modal number of PE-PC sessions was five (SD = 1.98). Providers previously trained in both PE and cognitive processing therapy (CPT) were more likely than providers who were not trained in either PE or CPT to have veterans complete PE-PC (OR = 1.54). Veterans with military sexual trauma were less likely to complete PE-PC than veterans with combat trauma (OR = 0.42). Asian American and Pacific Islander veterans were more likely than White veterans to complete treatment (OR = 2.93). Older veterans were more likely than younger veterans to complete treatment (OR = 1.11). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Change in posttraumatic stress disorder-related thoughts during treatment: Do thoughts drive change when pills are involved?

Posttraumatic negative thoughts about one's self and the world are related to posttraumatic stress disorder (PTSD) symptom severity and change in cognitive behavioral treatment (CBT), but little is known about this association when CBT is delivered with medication. The current study presents a planned comparison of changes in negative posttraumatic thoughts during (a) prolonged exposure (PE) plus pill placebo (PE+PLB), (b) sertraline plus enhanced medication management (SERT+EMM), and (c) PE plus sertraline (PE+SERT) as part of a randomized clinical trial in a sample of 176 veterans. Lagged regression modeling revealed that change in posttraumatic negative thoughts was associated with PTSD symptom change in the conditions in which participants received sertraline, ds = 0.14-0.25, ps = 0.04-.001). However, contrary to previous research, the models that started with symptom change were also statistically significant, d = 0.23, p < .001, for the lagged effect of symptoms on negative thoughts about self in the SERT+EMM condition, indicating a bidirectional association between such thoughts and PTSD symptoms. In the PE+PLB condition, no significant association between posttraumatic thoughts and PTSD symptoms emerged in either direction. These results suggest that the previously demonstrated role of change in posttraumatic thoughts leading to PTSD symptom reduction in PE may be altered when combined with pill administration, either active or placebo.

Predictors of Response to Prolonged Exposure, Sertraline, and Their Combination for the Treatment of Military PTSD.

Objective: The current study is an analysis of predictors of posttraumatic stress disorder (PTSD) treatment response in a clinical trial comparing (1) prolonged exposure plus placebo (PE + PLB), (2) PE + sertraline (PE + SERT), and (3) sertraline + enhanced medication management (SERT + EMM) with predictors including time since trauma (TST), self-report of pain, alcohol use, baseline symptoms, and demographics.Methods: Participants (N = 196) were veterans with combat-related PTSD (DSM-IV-TR) of at least 3 months' duration recruited between 2012 and 2016 from 4 sites in the 24-week PROlonGed ExpoSure and Sertraline (PROGrESS) clinical trial (assessments at weeks 0 [intake], 6, 12, 24, 36, and 52).Results: Across treatment conditions, (1) longer TST was predictive of greater week 24 PTSD symptom improvement (ß = 1.72, P = .01) after adjusting for baseline, (2) higher baseline pain severity was predictive of smaller symptom improvement (ß = -2.96, P = .003), and (3) Hispanic patients showed greater improvement than non-Hispanic patients (ß = 12.33, P = .03). No other baseline characteristics, including alcohol consumption, were significantly predictive of week 24 improvement. Comparison of TST by treatment condition revealed a significant relationship only in those randomized to the PE + SERT condition (ß = 2.53, P = .03). Longitudinal analyses showed similar results.Conclusions: The finding that longer TST shows larger symptom reductions is promising for PTSD patients who might not seek help for years following trauma. Higher baseline pain severity robustly predicted attenuated and slower response to all treatment conditions, suggesting a common neuropathologic substrate. Finally, in the current study, alcohol use did not impede the effectiveness of pharmacotherapy for PTSD.Trial Registration: ClinicalTrials.gov identifier: NCT01524133.

Residual symptoms of PTSD following Sertraline plus enhanced medication management, Sertraline plus PE, and PE plus placebo.

Although prolonged exposure (PE) and SSRI antidepressants are effective in treating posttraumatic stress disorder (PTSD), previous studies have shown that some symptoms tend to persist. The current study compared sertraline hydrochloride plus enhanced medication management (EMM), PE plus placebo, or PE plus sertraline hydrochloride in the likelihood of each individual PTSD symptom persisting in veterans with a PTSD diagnosis. We compared the likelihood of individual PTSD symptoms persisting in those with versus without a PTSD diagnosis at posttreatment. We found no significant differences across conditions in which symptoms were likely to persist posttreatment. Among those without a PTSD diagnosis at posttreatment, sleeping difficulties (63.0%), hypervigilance (47.3%), and nightmares (45.0%) were most likely to persist. Findings indicate no consistent differences in residual symptoms between PE and medications, and shared decision making with patients is encouraged in selecting treatments. Gold standard treatments (e.g., CBT-I) may be warranted for residual symptoms like insomnia.

Combat-Related Posttraumatic Stress Disorder and Comorbid Major Depression in U.S. Veterans: The Role of Deployment Cycle Adversity and Social Support.

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) commonly co-occur in combat veterans, and this comorbidity has been associated with higher levels of distress and more social and economic costs compared to one disorder alone. In a secondary analysis of a multisite randomized controlled trial of a sample of veterans with combat-related PTSD, we examined the associations among pre-, peri-, and postdeployment adversity, social support, and clinician-diagnosed comorbid MDD. Participants completed the Deployment Risk and Resilience Inventory and the Beck Depression Inventory-II as well as structured clinical interviews for diagnostic status. Among 223 U.S. veterans of the military operations in Iraq and Afghanistan (86.9% male) with primary combat-related PTSD, 69.5% had current comorbid MDD. After adjustment for sex, a linear regression model indicated that more concerns about family disruptions during deployment, f2 = 0.065; more harassment during deployment, f2 = 0.020; and lower ratings of postdeployment social support, f2 = 0.154, were associated with more severe self-reported depression symptoms. Interventions that enhance social support as well as societal efforts to foster successful postdeployment reintegration are critical for reducing the mental health burden associated with this highly prevalent comorbidity in veterans with combat-related PTSD.

Efficacy of Prolonged Exposure Therapy, Sertraline Hydrochloride, and Their Combination Among Combat Veterans With Posttraumatic Stress Disorder: A Randomized Clinical Trial.

Importance: Meta-analyses of treatments for posttraumatic stress disorder (PTSD) suggest that trauma-focused psychotherapies produce greater benefits than antidepressant medications alone. Objective: To determine the relative efficacy of prolonged exposure therapy plus placebo, prolonged exposure therapy plus sertraline hydrochloride, and sertraline plus enhanced medication management in the treatment of PTSD. Design, Setting, and Participants: The Prolonged Exposure and Sertraline Trial was a randomized, multisite, 24-week clinical trial conducted at the Veterans Affairs Ann Arbor Healthcare System, Veterans Affairs San Diego Healthcare System, Ralph H. Johnson Veterans Affairs Medical Center, and Massachusetts General Hospital Home Base Veterans Program between January 26, 2012, and May 9, 2016. Participants and clinicians were blinded to pill condition, and outcome evaluators were blinded to assignment. Participants completed assessments at weeks 0 (intake), 6, 12, 24, and 52 (follow-up). Participants (N = 223) were service members or veterans of the Iraq and/or Afghanistan wars with combat-related PTSD and significant impairment (Clinician-Administered PTSD Scale score, ≥50) of at least 3 months' duration. Analyses were on an intent-to-treat basis. Intervention: Participants completed up to thirteen 90-minute sessions of prolonged exposure therapy by week 24. Sertraline dosage was titrated during a 10-week period and continued until week 24; medication management was manualized. Main Outcomes and Measures: The primary outcome was symptom severity of PTSD in the past month as assessed by the Clinician-Administered PTSD Scale score at week 24. Results: Of 223 randomized participants, 149 completed the study at 24 weeks, and 207 (180 men and 27 women; mean [SD] age, 34.5 [8.3 years]) were included in the intent-to-treat analysis. Modified intent-to-treat analysis using a mixed model of repeated measures showed that PTSD symptoms decreased significantly during the 24 weeks (sertraline plus enhanced medication management, 33.8 points; prolonged exposure therapy plus sertraline, 32.7 points; and prolonged exposure therapy plus placebo, 29.4 points; ß,-9.39; 95% CI, -11.62 to -7.16; P < .001); however, slopes did not differ by treatment group (prolonged exposure therapy plus placebo group, -9.39; sertraline plus enhanced medication management group, -10.37; and prolonged exposure therapy plus sertraline group, -9.99; P = .81). Conclusions and Relevance: No difference in change in PTSD symptoms or symptom severity at 24 weeks was found between sertraline plus enhanced medication management, prolonged exposure therapy plus placebo, and prolonged exposure therapy plus sertraline. Trial Registration: ClinicalTrials.gov Identifier: NCT01524133.

Integrating biological treatment mechanisms into randomized clinical trials: Design of PROGrESS (PROlonGed ExpoSure and Sertraline Trial).

Increased emphasis on mechanisms of treatment effectiveness, biomarker predictors, and objective indicators of treatment response has sparked interest in integrated, translational treatment outcomes trials. The PROlonGed ExpoSure and Sertraline Trial (PROGrESS) is one such randomized controlled trial (RCT) focused on a key question in clinical management of posttraumatic stress disorder (PTSD) - the comparative and combined effectiveness of medication and psychotherapy. PROGrESS employs a state of the art trial design to examine psychotherapy and medication effects across three conditions: 1) Prolonged Exposure (PE) plus pill placebo, 2) Sertraline (SERT) plus Enhanced Medication Management (EMM), and 3) Combined treatment (PE/SERT). Innovative measures will capture potential biomarker predictors and indicators of treatment response within and across these three treatment conditions in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) service members and veterans with PTSD. Assessments include clinician-rated measures, self-report outcome measures, saliva for salivary cortisol and cortisol response to awakening at six assessment points, blood at baseline and week 24 for genetic and genomic analysis, as well as resting state connectivity and emotion processing and regulation using functional Magnetic Resonance Imaging (fMRI) paradigms in a subsample of veterans. Accordingly, the current study is designed to provide pragmatic clinical direction for the delivery of PTSD treatment through its primary outcomes in an effectiveness design, and will also provide informative results to elucidate underlying mechanisms and biomarkers involved in PTSD treatment response.

The loss of a fellow service member: Complicated grief in post-9/11 service members and veterans with combat-related posttraumatic stress disorder.

Bereavement is a potent and highly prevalent stressor among service members and veterans. However, the psychological consequences of bereavement, including complicated grief (CG), have been minimally examined. Loss was assessed in 204 post-9/11, when service members and veterans with combat-related posttraumatic stress disorder (PTSD) took part in a multicenter treatment study. Those who reported the loss of an important person completed the inventory of complicated grief (ICG; n = 160). Over three quarters (79.41%) of the sample reported an important lifetime loss, with close to half (47.06%) reporting the loss of a fellow service member (FSM). The prevalence of CG was 24.75% overall, and nearly one third (31.25%) among the bereaved. CG was more prevalent among veterans who lost a fellow service member (FSM) (41.05%, n = 39) compared to those bereaved who did not (16.92%, n = 11; OR = 3.41, 95% CI: 1.59, 7.36). CG was associated with significantly greater PTSD severity, functional impairment, trauma-related guilt, and lifetime suicide attempts. Complicated grief was prevalent and associated with adverse psychosocial outcomes in veterans and service members with combat-related PTSD. Clinicians working with this population should inquire about bereavement, including loss of a FSM, and screen for CG. Additional research examining CG in this population is needed.

Reducing suicidal ideation through evidence-based treatment for posttraumatic stress disorder.

BACKGROUND: Suicide is a major public health concern in military and civilian contexts. Veteran populations are at increased risk for suicide, especially veterans with mental health disorders such as Posttraumatic Stress Disorder (PTSD). Suicidal ideation (SI) is a primary risk factor for suicide. METHODS: We investigated changes in SI in a multi-site sample of treatment seeking veterans from three separate Veterans Health Administration (VA) medical centers (n = 289) who received Prolonged Exposure (PE) therapy, an evidence-based treatment (EBT) for PTSD. SI and PTSD symptoms were assessed, using self-report instruments, throughout routine clinical care. RESULTS: Both PTSD and SI symptoms reduced over the course of treatment (d-type effect sizes of 1.47 and 0.27, respectively). While SI was associated with PTSD symptoms at all time points, appropriately specified, time lagged models indicated that changes in PTSD symptoms were predictive of future declines in SI, while the converse was not true. CONCLUSIONS: Results indicate that treating PTSD symptoms with an EBT for PTSD can be an effective way to reduce SI, at least partially, and for some patients. These data are significant in light of the resources and programming devoted to addressing SI in the VA relative to available empirical evidence regarding the effectiveness of developed strategies. The findings demonstrate the importance of facilitating EBT referrals for specific disorders as a component of broad-based suicide outreach and preventions strategies.