Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

This study describes the three-phase development and validation of the Inventory of Psychosocial Functioning (IPF), an 80-item, self-report measure of posttraumatic stress disorder (PTSD)-related psychosocial functional impairment. In Phase I, we conducted 12 focus groups with male and female veterans (n = 53) to identify and operationalize the domains of psychosocial impairment associated with PTSD. This information was used to develop the IPF. We subsequently evaluated the psychometric properties of the newly developed inventory in Phases II (n = 276) and III (n = 368) using two independent samples of veterans. We found that the overall IPF score demonstrated stronger correlations with measures of mental health-related impairment (all rs > |.39|; all ps < .05) and weaker correlations with measures of physical health-related impairment (all rs < |.29|; all ps < .05). Overall IPF scores were most strongly associated with PTSD and other disorders associated with the anxious-misery factor of the three-factor model of psychiatric comorbidity (all rs > .56; all ps < .05) and less strongly associated with disorders associated with the fear factor (all rs < .48; all ps < .05) and the externalizing factor (r = .16; p < .05). The IPF demonstrated strong test-retest reliability (r = .77; p < .05). Our results suggest that the IPF is a valid and reliable measure of PTSD-related psychosocial functional impairment. (PsycINFO Database Record

Although numerous longitudinal studies have examined heterogeneity in posttraumatic stress disorder (PTSD) symptom course, the long-term course of the disorder remains poorly understood. This study sought to understand and predict long-term PTSD symptom course among a nationwide sample of Operations Enduring Freedom and Iraqi Freedom veterans enrolled in Veterans Health Administration services. We assessed PTSD symptoms at 4 time points over approximately 4.5 years (M = 55.11 months, SD = 6.89). Participants (N = 1,353) with and without probable PTSD were sampled at a 3:1 ratio, and male and female veterans were sampled at a 1:1 ratio to fully explore the heterogeneity of PTSD symptom course and the effect of sex on symptom course. By coding time as years since index trauma, we estimated the course of PTSD symptoms over 20 years. Results indicate symptom course is most appropriately characterized by substantial heterogeneity. On average, veterans experienced initial PTSD symptom severity above the diagnostic threshold following trauma exposure, which was initially stable over time and later began to gradually improve. Although results indicate symptoms eventually began to decline, this effect was gradual; most participants continued to meet or exceed the PTSD provisional diagnostic threshold long after trauma exposure. We identified several predictors and correlates of symptom course, including Hispanic ethnicity, postdeployment social support, and co-occurring psychopathology. Results highlight the heterogeneous nature of PTSD symptom course following trauma exposure and the urgency of the need to ensure access to evidence-based care and to improve available treatments.

This study validated the Brief Inventory of Psychosocial Functioning (B-IPF), an abridged version of the 80-item Inventory of Psychosocial Functioning (IPF; Bovin et al., 2018). The B-IPF—a 7-item self-report questionnaire that assesses posttraumatic stress disorder (PTSD)–related psychosocial functional impairment—was developed for use in settings in which the full IPF would be too time intensive to administer. In this study, we examined the psychometric properties of the B-IPF among a sample of 362 veterans recruited from 2 Veterans Affairs hospitals. The B-IPF demonstrated high internal consistency (Cronbach’s alpha = .84) and adequate test-retest reliability (r = .65, p < .001). The B-IPF was strongly correlated with the IPF (r = .71, p < .01) and had higher correlations with measures of mental health impairment and quality of life (all rs > ∥.50∥; all ps < .001) than with a measure of physical health impairment (i.e., the Physical Component Summary; r = −.34; p < .001), which demonstrated strong construct validity. In addition, the B-IPF displayed strong criterion-related validity, with higher correlations with a PTSD symptom measure, (r = .63, p < .05), and measures of other internalizing disorders (all rs > .44; all ps < .05) and a lower correlation with a measure of an externalizing disorder (r = .14; p < .05). These results indicate that the B-IPF is a reliable and valid instrument for assessing PTSD-related impairment. The strong psychometric properties of the instrument, in addition to its length, make it ideal for settings in which time is a factor.