JAMA Psychiatry. 2025 Oct 15. doi: 10.1001/jamapsychiatry.2025.2962. Online ahead of print.
ABSTRACT
IMPORTANCE: There have only been 3 efficacy trials reporting head-to-head comparisons of pharmacotherapy and trauma-focused psychotherapy for posttraumatic stress disorder (PTSD), and none were conducted in primary care. In addition, few trials have examined treatment sequences for patients not responding to an initial treatment.
OBJECTIVE: To test the hypothesis that (1) brief trauma-focused psychotherapy (written exposure therapy [WET]) is more effective than a choice of 3 selective serotonin reuptake inhibitors (SSRIs; ie, sertraline, fluoxetine, or paroxetine) and (2) WET augmentation is more effective than switching to the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine for those not responding to an SSRI.
DESIGN, SETTING, AND PARTICIPANTS: This was a pragmatic comparative effectiveness trial conducted from April 2021 to June 2024 that randomized primary care patients to 1 of 3 treatment sequences: (1) SSRI followed by WET augmentation, (2) SSRI followed by switch to SNRI, or (3) WET followed by SSRI. Effectiveness in this pragmatic trial depends on treatment engagement and treatment fidelity. The study included patients meeting clinical criteria for PTSD from primary care clinics of 7 federally qualified health centers and 8 Department of Veterans Affairs medical centers.
INTERVENTIONS: SSRI followed by WET augmentation, SSRI followed by switch to SNRI, or WET followed by SSRI.
MAIN OUTCOMES AND MEASURES: PTSD symptom severity, as measured by the DSM-5 PTSD Checklist (PCL-5).
RESULTS: A total of 700 patients (mean [SD] age, 45.1 [15.4] years; 368 men [62.1%]). The mean (SD) baseline PCL-5 score was 52.8 (11.1), indicating considerable symptom severity. At 4 months, 144 of 278 patients (51.8%) randomized to an SSRI were adherent and reported a 14.0-point PCL-5 decrease, whereas 11 of 352 patients (31.5%) randomized to WET completed all sessions and reported a 12.1-point decrease. There was no significant between-group difference (adjusted mean difference [MD], 1.79; 95% CI, -0.76 to 4.34; P = .17). For the 122 of 295 patients (41.4%) randomized to an SSRI who did not respond to treatment, those randomized to switch to the SNRI reported a 9.2-point PCL-5 decrease compared with a 2.3-point decrease for those randomized to WET augmentation, which was a statistically significant between-group difference (adjusted MD, 10.19; 95% CI, 4.97-15.41; P < .001).
CONCLUSIONS AND RELEVANCE: Study results showed that treatment of PTSD in primary care with either SSRIs or WET was feasible and effective. For patients not responding to an SSRI, switching to an SNRI may be more effective than WET augmentation.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04597190.
PMID:41091477 | DOI:10.1001/jamapsychiatry.2025.2962
