Dataset Information

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

ABSTRACT:

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; β,-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.

SUBMITTER: Rauch SAM

PROVIDER: S-EPMC6439753 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Recent work inspired by graph theory has begun to conceptualize mental disorders as networks of interacting symptoms. Posttraumatic stress disorder (PTSD) symptom networks have been investigated in clinical samples meeting full diagnostic criteria, including military veterans, natural disaster survivors, civilian survivors of war, and child sexual abuse survivors. Despite reliable associations across reported networks, more work is needed to compare central symptoms across trauma types. Additionally, individuals without a diagnosis who still experience symptoms, also referred to as subthreshold cases, have not been explored with network analysis in veterans. A sample of 1,050 Iraq/Afghanistan-era U.S. military veterans (851 males, mean age = 36.3, SD = 9.53) meeting current full-criteria PTSD (n = 912) and subthreshold PTSD (n = 138) were assessed with the Structured Clinical Interview for DSM-IV Disorders (SCID). Combat Exposure Scale (CES) scores were used to group the sample meeting full-criteria into high (n = 639) and low (n = 273) combat exposure subgroups. Networks were estimated using regularized partial correlation models in the R-package qgraph, and robustness tests were performed with bootnet. Frequently co-occurring symptom pairs (strong network connections) emerged between two avoidance symptoms, hypervigilance and startle response, loss of interest and detachment, as well as, detachment and restricted affect. These associations replicate findings reported across PTSD trauma types. A symptom network analysis of PTSD in a veteran population found significantly greater overall connectivity in the full-criteria PTSD group as compared to the subthreshold PTSD group. Additionally, novel findings indicate that the association between intrusive thoughts and irritability is a feature of the symptom network of veterans with high levels of combat exposure. Mean node predictability is high for PTSD symptom networks, averaging 51.5% shared variance. With the tools described here and by others, researchers can help refine diagnostic criteria for PTSD, develop more accurate measures for assessing PTSD, and eventually inform therapies that target symptoms with strong network connections to interrupt interconnected symptom complexes and promote functional recovery.

Project description:ImportancePosttraumatic stress disorder (PTSD) is a prevalent and serious mental health problem. Although there are effective psychotherapies for PTSD, there is little information about their comparative effectiveness.ObjectiveTo compare the effectiveness of prolonged exposure (PE) vs cognitive processing therapy (CPT) for treating PTSD in veterans.Design, setting, and participantsThis randomized clinical trial assessed the comparative effectiveness of PE vs CPT among veterans with military-related PTSD recruited from outpatient mental health clinics at 17 Department of Veterans Affairs medical centers across the US from October 31, 2014, to February 1, 2018, with follow-up through February 1, 2019. The primary outcome was assessed using centralized masking. Tested hypotheses were prespecified before trial initiation. Data were analyzed from October 5, 2020, to May 5, 2021.InterventionsParticipants were randomized to 1 of 2 individual cognitive-behavioral therapies, PE or CPT, delivered according to a flexible protocol of 10 to 14 sessions.Main outcomes and measuresThe primary outcome was change in PTSD symptom severity on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from before treatment to the mean after treatment across posttreatment and 3- and 6-month follow-ups. Secondary outcomes included other symptoms, functioning, and quality of life.ResultsAnalyses were based on all 916 randomized participants (730 [79.7%] men and 186 [20.3%] women; mean [range] age 45.2 [21-80] years), with 455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95% CI, 39.1-40.7] points) and 461 participants randomized to CPT (mean CAPS-5 score at baseline, 40.3 [95% CI, 39.5-41.1] points). PTSD severity on the CAPS-5 improved substantially in both PE (standardized mean difference [SMD], 0.99 [95% CI, 0.89-1.08]) and CPT (SMD, 0.71 [95% CI, 0.61-0.80]) groups from before to after treatment. Mean improvement was greater in PE than CPT (least square mean, 2.42 [95% CI, 0.53-4.31]; P = .01), but the difference was not clinically significant (SMD, 0.17). Results for self-reported PTSD symptoms were comparable with CAPS-5 findings. The PE group had higher odds of response (odds ratio [OR], 1.32 [95% CI, 1.00-1.65]; P < .001), loss of diagnosis (OR, 1.43 [95% CI, 1.12-1.74]; P < .001), and remission (OR, 1.62 [95% CI, 1.24-2.00]; P < .001) compared with the CPT group. Groups did not differ on other outcomes. Treatment dropout was higher in PE (254 participants [55.8%]) than in CPT (215 participants [46.6%]; P < .01). Three participants in the PE group and 1 participant in the CPT group were withdrawn from treatment, and 3 participants in each treatment dropped out owing to serious adverse events.Conclusions and relevanceThis randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups. These findings highlight the importance of shared decision-making to help patients understand the evidence and select their preferred treatment.Trial registrationClinicalTrials.gov Identifier: NCT01928732.