Meta-analyses of treatments for posttraumatic stress disorder (PTSD) suggest that trauma-focused psychotherapies produce greater benefits than antidepressant medications alone.
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.
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.
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.
The primary outcome was symptom severity of PTSD in the past month as assessed by the Clinician-Administered PTSD Scale score at week 24.
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).
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.
ClinicalTrials.gov Identifier: NCT01524133.
Rationale
3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these ...effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA’s broad pharmacological profile, further investigation is warranted before moving to a complex clinical population.
Objectives
We aimed to inform clinical research by providing a translational model of MDMA’s effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction.
Methods
We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training.
Results
MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA’s effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA’s effect by 5-HTT inhibition also downregulated 5-HT
2A
-mediated behavior, and 5-HT
2A
antagonism disrupted MDMA’s effect on extinction.
Conclusions
We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT
2A
receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.
Leveraging technology to provide evidence‐based therapy for posttraumatic stress disorder (PTSD), such as prolonged exposure (PE), during the COVID‐19 pandemic helps ensure continued access to ...first‐line PTSD treatment. Clinical video teleconferencing (CVT) technology can be used to effectively deliver PE while reducing the risk of COVID‐19 exposure during the pandemic for both providers and patients. However, provider knowledge, experience, and comfort level with delivering mental health care services, such as PE, via CVT is critical to ensure a smooth, safe, and effective transition to virtual care. Further, some of the limitations associated with the pandemic, including stay‐at‐home orders and physical distancing, require that providers become adept at applying principles of exposure therapy with more flexibility and creativity, such as when assigning in vivo exposures. The present paper provides the rationale and guidelines for implementing PE via CVT during COVID‐19 and includes practical suggestions and clinical recommendations.
According to current treatment guidelines for Complex PTSD (cPTSD), psychotherapy for adults with cPTSD should start with a “stabilization phase.” This phase, focusing on teaching self‐regulation ...strategies, was designed to ensure that an individual would be better able to tolerate trauma‐focused treatment. The purpose of this paper is to critically evaluate the research underlying these treatment guidelines for cPTSD, and to specifically address the question as to whether a phase‐based approach is needed. As reviewed in this paper, the research supporting the need for phase‐based treatment for individuals with cPTSD is methodologically limited. Further, there is no rigorous research to support the views that: (1) a phase‐based approach is necessary for positive treatment outcomes for adults with cPTSD, (2) front‐line trauma‐focused treatments have unacceptable risks or that adults with cPTSD do not respond to them, and (3) adults with cPTSD profit significantly more from trauma‐focused treatments when preceded by a stabilization phase. The current treatment guidelines for cPTSD may therefore be too conservative, risking that patients are denied or delayed in receiving conventional evidence‐based treatments from which they might profit.
Epigenetic alterations in DNA methylation might mediate gene expression effects of trauma underlying PTSD symptoms, or effects of PTSD on related health problems. PTSD is associated with all-cause ...morbidity and premature mortality, suggesting accelerated biological aging. We measured genome-wide DNA methylation (Illumina MethylationEPIC BeadChip) in whole blood in a treatment study for combat-related PTSD - "PROGrESS", a multisite RCT comparing sertraline plus enhanced medication management (SERT + EMM), prolonged exposure (PE) therapy plus placebo (PE + PLB), and the combination (SERT + PE). DNA methylation was measured in 140 US military veterans who served in Iraq and/or Afghanistan (112 current PTSD cases enrolled in a PTSD treatment study and 28 veterans without PTSD history controls), and also 59 non-trauma exposed controls at baseline posttreatment (24 weeks after baseline). Increased DNA methylation GrimAge acceleration (p = 8.8e-09) was observed in patients with PTSD compared to a pooled control group (trauma exposed and non-trauma exposed), suggesting a higher risk of premature mortality in those with PTSD. There was no difference in GrimAge acceleration between combat trauma and non-trauma exposed controls. No treatment-related changes in GrimAge acceleration were found in within-subject comparisons of PTSD patients pre- to post-treatment.
Highlights • Hierarchical linear modeling demonstrated habituation between sessions. • High responders showed greater between-session habituation. • High responders did not show differential ...within-session habituation. • Tracking SUDS changes across sessions can help practitioners monitor progress.
Prolonged exposure (PE) therapy is a first-line treatment for posttraumatic stress disorder (PTSD) and involves repeated presentation of trauma-related cues without aversive outcomes. A primary ...learning mechanism of PE is fear extinction (new learning that a dangerous cue is now safe) and its retention (maintaining this new learning over time). Extant research suggests extinction is impaired in PTSD patients. In this study, we employed an established fear-potentiated startle-based paradigm to examine fear acquisition, extinction learning and retention before and after completion of intensive outpatient treatment. First, PTSD patients undergoing PE (n = 55) were compared to trauma-exposed patients without PTSD (n = 57). We identified excessive fear in PTSD patients during acquisition and extinction before treatment compared to non-PTSD patients. At post-treatment, we examined the return of fear after extinction in PTSD patients showing high or low treatment response to PE (≥50% change in PTSD symptom severity vs. < 50%). High PE responders maintained fear extinction learning whereas low PE responders showed significant return of fear at post-treatment. These results replicate and extend previous findings of impaired extinction in PTSD and provide support for the proposed theoretical link between fear extinction and PE response.
•Fear conditioning and extinction paradigms can model traumatic fear learning.•Fear extinction learning is often impaired in PTSD patients.•Extinction-based intensive outpatient exposure therapy can effectively treat PTSD.•Improved laboratory extinction learning is linked to reduced clinical PTSD symptoms.
Objective
To conduct a quality improvement evaluation of the Empower Veterans Program (EVP), an interdisciplinary pain rehabilitation/functional restoration program option for functional restoration ...for high‐impact chronic pain, offered in a large metro‐area Veterans Health Administration (VHA) system.
Data Sources
VHA Corporate Data Warehouse electronic medical record data for patients treated by EVP between 2015 and 2019.
Evaluation Design
This retrospective design first compared EVP patients considered engaged or not engaged in completing treatment in terms of demographic characteristics and post‐treatment changes in clinical measures related to opioid use and mental health. We then compared mortality risk between matched groups of treated and untreated patients with chronic pain and concurrent opioid prescriptions using propensity score matching and Cox proportional hazards methods. “Treated” in the matched groups was defined as any level of EVP participation (i.e., both engaged and not engaged).
Data Collection/Extraction Methods
We first identified 1053 EVP patients with 1 year of pre‐and post‐treatment follow‐time and determined their engagement level. From those with chronic pain and prescription opioids, we matched 237 EVP patients to 375 untreated patients.
Principal Findings
Engaged patients (57.4% of treated patients), were somewhat older than the non‐engaged (mean age 57.1 vs. 53.7, Cohen's D = 0.30), and achieved lower mean PHQ9 depression scores in the post‐treatment year (9.2 vs. 10.6, Cohen's D = 0.20). Participation in EVP was associated with a 65% lower mortality risk among Veterans with chronic pain and opioid use when compared to the untreated patients: (HR: 0.35, 95% CI: 0.17, 0.75).
Conclusions
EVP was associated with a large reduction in mortality risk for Veterans with both chronic pain and opioid use. This result could inform the decision process in a VA station or region when considering providing or expanding access to an interdisciplinary rehabilitation/functional restoration program for chronic pain.
Background
“Mindfulness‐based” interventions show promise for stress reduction in general medical conditions, and initial evidence suggests that they are accepted in trauma‐exposed individuals. ...Mindfulness‐based cognitive therapy (MBCT) shows substantial efficacy for prevention of depression relapse, but it has been less studied in anxiety disorders. This study investigated the feasibility, acceptability, and clinical outcomes of an MBCT group intervention adapted for combat posttraumatic stress disorder (PTSD).
Methods
Consecutive patients seeking treatment for chronic PTSD at a VA outpatient clinic were enrolled in 8‐week MBCT groups, modified for PTSD (four groups, n = 20) or brief treatment‐as‐usual (TAU) comparison group interventions (three groups, n = 17). Pre and posttherapy psychological assessments with clinician administered PTSD scale (CAPS) were performed with all patients, and self‐report measures (PTSD diagnostic scale, PDS, and posttraumatic cognitions inventory, PTCI) were administered in the MBCT group.
Results
Intent to treat analyses showed significant improvement in PTSD (CAPS (t(19) = 4.8, P < .001)) in the MBCT condition but not the TAU conditions, and a significant Condition × Time interaction (F1,35 = 16.4, P < .005). MBCT completers (n = 15, 75%) showed good compliance with assigned homework exercises, and significant and clinically meaningful improvement in PTSD symptom severity on posttreatment assessment in CAPS and PDS (particularly in avoidance/numbing symptoms), and reduced PTSD‐relevant cognitions in PTCI (self blame).
Conclusions
These data suggest group MBCT as an acceptable brief intervention/adjunctive therapy for combat PTSD, with potential for reducing avoidance symptom cluster and PTSD cognitions. Further studies are needed to examine efficacy in a randomized controlled design and to identify factors influencing acceptability and efficacy.
Background: Food addiction (FA) is a dysregulated eating pattern characterized by difficulties in controlling the intake of certain foods. There is an overlap in physical and mental health correlates ...of FA and post-traumatic stress disorder (PTSD). The purpose of this study was to examine sex differences in the rates of positive FA status in individuals with threshold/subthreshold PTSD, and to examine sex differences in the physical and mental health correlates of FA. Methods: Post-9/11 veterans/service members seeking PTSD treatment were recruited. Participants were diagnosed with PTSD via the administration of a clinical interview. FA status was determined using Modified Yale Food Addiction Scale-2, binary sex and body mass index were assessed with demographics questions. Results: Nearly half (43%) of the sample were women. There were no sex differences in the rates of FA, with an overall FA prevalence of 18%. There were no sex differences in FA symptom count in the whole sample (M = 1.63) or those with FA status (M = 6.21). Individuals with FA reported higher frequency of disordered eating, higher severity of PTSD, and depression symptoms. Conclusions: FA should be assessed in tandem with PTSD symptoms, as its prevalence in that sample is higher than in the general population, and it appears to affect both sexes at similar rates.
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