Improvement In Posttraumatic Stress Disorder Symptoms Research Articles

Neuroimaging correlates and predictors of response to repeated-dose intravenous ketamine in PTSD: preliminary evidence.

Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants of a randomized clinical trial of repeated-dose intravenous ketamine vs midazolam (total N = 21). In a pre-registered analysis, we tested whether changes in an a priori set of imaging measures from a target neural circuit were predictive of improvement in PTSD symptoms, using leave-one-out cross-validated elastic-net regression models (regions of interest in the target circuit consisted of the dorsal and rostral anterior cingulate cortex, ventromedial prefrontal cortex, anterior hippocampus, anterior insula, and amygdala). Improvements in PTSD severity were associated with increased functional connectivity between the ventromedial prefrontal cortex (vmPFC) and amygdala during emotional face-viewing (change score retained in model with minimum predictive error in left-out subjects, standardized regression coefficient [β] = 2.90). This effect was stronger in participants who received ketamine compared to midazolam (interaction β = 0.86), and persisted following inclusion of concomitant change in depressive symptoms in the analysis model (β = 0.69). Improvement following ketamine was also predicted by decreased dorsal anterior cingulate activity during emotional conflict regulation, and increased task-free connectivity between the vmPFC and anterior insula (βs = -2.82, 0.60). Exploratory follow-up analysis via dynamic causal modelling revealed that whilst improvement in PTSD symptoms following either drug was associated with decreased excitatory modulation of amygdala→vmPFC connectivity during emotional face-viewing, increased top-down inhibition of the amygdala by the vmPFC was only observed in participants who improved under ketamine. Individuals with low prefrontal inhibition of amygdala responses to faces at baseline also showed greater improvements following ketamine treatment. These preliminary findings suggest that, specifically under ketamine, improvements in PTSD symptoms are accompanied by normalization of hypofrontal control over amygdala responses to social signals of threat.

Temporal Relationship Between Change in Subjective Distress and PTSD Symptom Decrease During Prolonged Exposure Therapy for Posttraumatic Stress Disorder

There is growing evidence that change in distress is an indicator of change during Prolonged Exposure (PE) for posttraumatic stress disorder (PTSD). However, temporal sequencing studies investigating whether change in distress precedes PTSD symptom decline are lacking. These studies are essential since the timeline between indicators of change and treatment outcome is a key assumption for mediation. The aim of the present study was to assess the temporal relationship between within- and between-session change in subjective distress and PTSD symptom decrease. We analyzed session data from 86 patients with PTSD. Data were analyzed using dynamic panel models. We distinguished temporal effects (within-persons) from averaged effects (between-persons). Results regarding the temporal effect showed that within-session change in subjective distress preceded PTSD symptom improvement while the reversed effect was absent. Averaged within-session change in subjective distress was also related to PTSD symptom improvement. Results regarding the temporal effect of between-session change in subjective distress showed that it did not precede PTSD symptom improvement. Averaged between-session change in subjective distress was related to PTSD symptom improvement. This study provides evidence for within- but not between-session change in subjective distress as indicator of change during PE. We also found that the way of modeling potential indicators of change affects results and implications. We recommend future studies to analyze mediators during treatment using temporal rather than averaged effects.

A randomized, double-blind, placebo-controlled trial of hydrocortisone augmentation of Prolonged Exposure for PTSD in U.S. combat veterans

ObjectiveCognitive behavioral therapies such as Prolonged Exposure (PE) are considered first line treatments for posttraumatic stress disorder (PTSD). Nonetheless, many continue to experience significant symptoms following treatment and there is interest in enhancing treatment effectiveness. Glucocorticoid alterations in PTSD are well documented, and these steroids have been shown to enhance extinction learning. MethodsAugmentation of PE with the synthetic glucocorticoid hydrocortisone (HCORT) was tested in a randomized, double-blind, placebo-controlled trial in 60 veterans of wars in Iraq or Afghanistan with PTSD (NCT01525680). Participants ingested 30 mg oral HCORT or placebo 30 min prior to exposure sessions. Primary outcome measure: PTSD severity assessed by the CAPS; secondary outcome measures: self reported PTSD symptoms assessed by the PDS and depression assessed by the BDI; all administered at pretreatment, posttreatment, and 3-month follow up. ResultsAcross conditions, there was a robust effect of PE over time. An intent-to-treat analysis showed that HCORT did not measurably improve PTSD symptoms or secondary outcomes. However, exploratory analyses indicated that veterans with mild TBI exposure and current postconcussive symptoms showed a greater reduction in hyperarousal symptoms following PE treatment with HCORT augmentation. Additionally, veterans with higher baseline glucocorticoid sensitivity showed a greater reduction in avoidance symptoms with HCORT augmentation. ConclusionsTreatment matching based on cognitive or biological vulnerabilities might lead to greater efficacy of PE with glucocorticoid augmentation.

Initial outcomes of couple HOPES: A guided online couple intervention for PTSD and relationship enhancement

Couple HOPES (Helping Overcome PTSD and Enhance Satisfaction) is a guided, online couple intervention adapted from Cognitive-Behavioral Conjoint Therapy for posttraumatic stress disorder (PTSD). It was created to overcome a range of barriers to accessing evidence-based treatments for PTSD and the intimate relationship problems associated with it. This manuscript describes initial outcomes of the intervention in a series of 10 couples. Participants were military, veteran and first responders with probable PTSD and their intimate partners. Couples completed the program and measurements of PTSD, relationship satisfaction, and secondary outcomes at pre-, mid-, and post-intervention. Mean satisfaction for the program was high and it was completed by seven of ten couples. Participants with PTSD evidenced significant and large pre- to post-intervention effect size improvements in PTSD symptoms (g = 0.80) and perceived health (g = 1.13). They also exhibited non-significant but medium effect size pre- to post-intervention improvements in quality of life (g = 0.62), and depression (g = 0.53), and small effect size pre- to post-intervention improvements in argumentativeness (g = 0.43), anger (g = 0.31), and anxiety (g = 0.31). Partners reported significant and moderate pre- to post-intervention effect size improvements in relationship satisfaction (g = 0.68), and medium but not significant effect size improvements in accommodation of PTSD (g = 0.56). Results provide initial support for the feasibility, acceptability, and efficacy of Couple HOPES for improving PTSD and relationship satisfaction. However, more testing in larger samples, including with randomized controlled designs, is needed.

Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder.

Sleep disturbances (SDs) are among the most distressing and commonly reported symptoms in posttraumatic stress disorder (PTSD). Despite increased attention on sleep in clinical PTSD research, SDs remain difficult to treat. In Phase 2 trials, 3,4‐methylenedioxymethamphetamine (MDMA)–assisted psychotherapy has been shown to greatly improve PTSD symptoms. We hypothesized that MDMA‐assisted psychotherapy would improve self‐reported sleep quality (SQ) in individuals with PTSD and be associated with declining PTSD symptoms. Participants in four studies (n = 63) were randomized to receive 2–3 sessions of active MDMA (75–125 mg; n = 47) or placebo/control MDMA (0–40 mg, n = 16) during all‐day psychotherapy sessions. The PSQI was used to assess change in SQ from baseline to the primary endpoint, 1–2 months after the blinded sessions. Additionally, PSQI scores were measured at treatment exit (TE) and 12‐month follow‐up. Symptoms of PTSD were measured using the CAPS‐IV. At the primary endpoint, CAPS‐IV total severity scores dropped more after active MDMA than after placebo/control (−34.0 vs. −12.4), p = .003. Participants in the active dose group showed more improvement in SQ compared to those in the control group (PSQI total score ΔM = −3.5 vs. 0.6), p = .003. Compared to baseline, SQ had improved at TE, p < .001, with further significant gains reported at 12‐month follow‐up (TE to 12‐months ΔM = −1.0), p = .030. Data from these randomized controlled double‐blind studies provide evidence for the beneficial effects of MDMA‐assisted psychotherapy in treating SDs in individuals with PTSD.

Baseline sleep quality moderates symptom improvement in veterans with comorbid PTSD and TBI receiving trauma-focused treatment

Poor sleep quality is common among Veterans with posttraumatic stress disorder (PTSD) and history of traumatic brain injury (TBI). However, the relationship between sleep quality and treatment outcomes following trauma-focused interventions is less well-understood in this population. We sought to better understand whether 1) sleep quality changed as a result of trauma-focused treatment and 2) if baseline sleep quality moderated psychological and neurobehavioral treatment outcomes. Our sample consisted of 100 Iraq/Afghanistan era Veterans with PTSD and history of mild to moderate TBI who were randomized to one of two trauma-focused treatments: 1) Cognitive Processing Therapy (CPT) or 2) combined CPT and Cognitive Symptom Management and Rehabilitation Therapy (SMART-CPT). Self-reported sleep quality, psychiatric symptoms (PTSD and depression), and neurobehavioral concerns were assessed at multiple timepoints throughout the study. Multilevel modeling showed sleep quality did not improve, regardless of treatment condition. However, worse baseline sleep quality was associated with less improvement in PTSD symptoms and cognitive complaints. There was no effect of baseline sleep quality on change in depression symptoms. These findings suggest that more targeted treatments to address sleep quality either prior to or in conjunction with trauma-focused therapy may help to improve treatment outcomes for Veterans with comorbid PTSD and TBI history.

Randomized, Placebo-Controlled Trial of the Angiotensin Receptor Antagonist Losartan for Posttraumatic Stress Disorder

BackgroundEvidence-based pharmacological treatments for posttraumatic stress disorder (PTSD) are few and of limited efficacy. Previous work suggests that angiotensin type 1 receptor inhibition facilitates fear inhibition and extinction, important for recovery from PTSD. This study tests the efficacy of the angiotensin type 1 receptor antagonist losartan, an antihypertensive drug, repurposed for the treatment of PTSD. MethodsA randomized controlled trial was conducted for 10 weeks in 149 men and women meeting DSM-5 PTSD criteria. Losartan (vs. placebo) was flexibly titrated from 25 to 100 mg/day by week 6 and held at highest tolerated dose until week 10. Primary outcome was the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) change score at 10 weeks from baseline. A key secondary outcome was change in CAPS-5 associated with a single nucleotide polymorphism of the ACE gene. Additional secondary outcomes included changes in the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9, and proportion of responders with a Clinical Global Impressions–Improvement scale of “much improved” or “very much improved.” ResultsBoth groups had robust improvement in PTSD symptoms, but there was no significant difference on the primary end point, CAPS-5 measured as week 10 change from baseline, between losartan and placebo (mean change difference, 0.9, 95% confidence interval, −3.2 to 5.0). There was no significant difference in the proportion of Clinical Global Impressions–Improvement scale responders for losartan (58.6%) versus placebo (57.9%), no significant differences in changes in PTSD Checklist for DSM-5 or Patient Health Questionnaire-9, and no association between ACE genotype and CAPS-5 improvement on losartan. ConclusionsAt these doses and durations, there was no significant benefit of losartan compared with placebo for the treatment of PTSD. We discuss implications for failure to determine the benefit of a repurposed drug with strong a priori expectations of success based on preclinical and epidemiological data.

Effectiveness and comparative effectiveness of evidence-based psychotherapies for posttraumatic stress disorder in clinical practice.

While evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) is a first-line treatment, its real-world effectiveness is unknown. We compared cognitive processing therapy (CPT) and prolonged exposure (PE) each to an individual psychotherapy comparator group, and CPT to PE in a large national healthcare system. We utilized effectiveness and comparative effectiveness emulated trials using retrospective cohort data from electronic medical records. Participants were veterans with PTSD initiating mental healthcare (N = 265 566). The primary outcome was PTSD symptoms measured by the PTSD Checklist (PCL) at baseline and 24-week follow-up. Emulated trials were comprised of 'person-trials,' representing 112 discrete 24-week periods of care (10/07-6/17) for each patient. Treatment group comparisons were made with generalized linear models, utilizing propensity score matching and inverse probability weights to account for confounding, selection, and non-adherence bias. There were 636 CPT person-trials matched to 636 non-EBP person-trials. Completing ⩾8 CPT sessions was associated with a 6.4-point greater improvement on the PCL (95% CI 3.1-10.0). There were 272 PE person-trials matched to 272 non-EBP person-trials. Completing ⩾8 PE sessions was associated with a 9.7-point greater improvement on the PCL (95% CI 5.4-13.8). There were 232 PE person-trials matched to 232 CPT person-trials. Those completing ⩾8 PE sessions had slightly greater, but not statistically significant, improvement on the PCL (8.3-points; 95% CI 5.9-10.6) than those completing ⩾8 CPT sessions (7.0-points; 95% CI 5.5-8.5). PTSD symptom improvement was similar and modest for both EBPs. Although EBPs are helpful, research to further improve PTSD care is critical.

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder and Major Depression: Comparing Commonly Used Clinical Protocols.

Transcranial magnetic stimulation (TMS) is increasingly being used to treat posttraumatic stress disorder (PTSD) comorbid with major depressive disorder (MDD). Yet, identifying the most effective stimulation parameters remains an active area of research. We recently reported on the use of 5 Hz TMS to reduce PTSD and MDD symptoms. A recently developed form of TMS, intermittent theta burst stimulation (iTBS), appears noninferior for treating MDD. Because iTBS can be delivered in a fraction of the time, it provides significant logistical advantages; however, evaluations of whether iTBS provides comparable PTSD and MDD symptom reductions are lacking. We performed a retrospective chart review comparing clinical outcomes in veterans with PTSD and MDD who received iTBS (n = 10) with a matched cohort that received 5‐Hz TMS (n = 10). Symptoms were evaluated using self‐reported rating scales at baseline and every five treatments for up to 30 sessions. Both protocols were safe and reduced symptoms, ps < .001, but veterans who received iTBS reported poorer outcomes. These results were observed using mixed‐model analyses, Group x Time interaction: p = .011, and effect sizes, where 5 Hz TMS demonstrated superior PTSD and MDD symptom improvement, ds = 1.81 and 1.51, respectively, versus iTBS, ds = 0.63 and 0.88, respectively. Data from prior controlled trials of iTBS, with increased stimulation exposure, have appeared to provide comparable clinical outcomes compared with 5 Hz TMS. Prospective and controlled comparisons are required; however, the present findings provide important information for clinicians using TMS to treat these commonly comorbid disorders.

736 Evaluation of suvorexant for trauma-related insomnia

Abstract Introduction Finding medication treatment that improves sleep disturbances with posttraumatic stress disorder (PTSD) has challenged the field of psychopharmacology with debate regarding the desirable profile of effects on sleep physiology. Evidence for fragmentation of REM sleep during the earlier stages of PTSD drew our interest to the first marketed dual orexin antagonist, suvorexant, which has been suggested in some studies to enhance REM sleep. This property has also raised concerns regarding potential exacerbation of nightmares and REM sleep related parasomnias. Insomnia is a common sequela of trauma exposure and can occur with and without other PTSD symptoms. The objective of our study was to evaluate the tolerability and preliminary efficacy of suvorexant for trauma related insomnia in a double blind, placebo controlled trial. Methods 64 met initial inclusion criteria and 42 participants had evaluable results. 65% were female, and 66% African-American, mean age was 35yrs.All participants were screened by the Duke Sleep Disorders Interview to met criteria for insomnia that began or was exacerbated following a DSM5 Criterion A trauma. Approximately a third of the study group met criteria for either current PTSD, past (remitted PTSD), or no PTSD, and 56% reported histories of traumatic nightmares hat generally had diminished from their initial severity. Results Medication intolerance was infrequent with one participant in the med group reporting mild sedation that precluded a dose increase to 20mg, and another, moderate sedation with feelings of derealization that led to discontinuation. There was no evidence for emerging nightmare symptoms or REM-related parasomnias. Overall there was significant improvement in sleep and PTSD symptoms in both the placebo and med group and a modest rise in REM sleep in the med group that did not differentiate statistically from placebo. Conclusion Our findings suggest that distressing trauma related insomnia can occur with and without PTSD and that suvorexant is well tolerated in this population. A larger and more symptomatic group is required to more definitively evaluate efficacy. Support (if any) supported by a grant from Merck (MISP 53678)

Resting-state connectivity subtype of comorbid PTSD and alcohol use disorder moderates improvement from integrated prolonged exposure therapy in Veterans.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and are associated with significant functional impairment and inconsistent treatment outcomes. Data-driven subtyping of this clinically heterogeneous patient population and the associated underlying neural mechanisms are highly needed to identify who will benefit from psychotherapy. In 53 comorbid PTSD/AUD patients, resting-state functional magnetic resonance imaging was collected prior to undergoing individual psychotherapy. We used a data-driven approach to subgroup patients based on directed connectivity profiles. Connectivity subgroups were compared on clinical measures of PTSD severity and heavy alcohol use collected at pre- and post-treatment. We identified a subgroup of patients associated with improvement in PTSD symptoms from integrated-prolonged exposure therapy. This subgroup was characterized by lower insula to inferior parietal cortex (IPC) connectivity, higher pregenual anterior cingulate cortex (pgACC) to posterior midcingulate cortex connectivity and a unique pgACC to IPC path. We did not observe any connectivity subgroup that uniquely benefited from integrated-coping skills or subgroups associated with change in alcohol consumption. Data-driven approaches to characterize PTSD/AUD subtypes have the potential to identify brain network profiles that are implicated in the benefit from psychological interventions - setting the stage for future research that targets these brain circuit communication patterns to boost treatment efficacy.

Changes in Brain Volume Associated with Trauma‐Focused Cognitive Behavioral Therapy Among Youth with Posttraumatic Stress Disorder

This study investigated group differences and longitudinal changes in brain volume before and after trauma-focused cognitive behavioral therapy (TF-CBT) in 20 unmedicated youth with maltreatment-related posttraumatic stress disorder (PTSD) and 20 non-trauma-exposed healthy control (HC) participants. We collected MRI scans of brain anatomy before and after 5 months of TF-CBT or the same time interval for the HC group. FreeSurfer software was used to segment brain images into 95 cortical and subcortical volumes, which were submitted to optimal scaling regression with lasso variable selection. The resulting model of group differences at baseline included larger right medial orbital frontal and left posterior cingulate corticies and smaller right midcingulate and right precuneus corticies in the PTSD relative to the HC group, R2 = .67. The model of group differences in pre- to posttreatment change included greater longitudinal changes in right rostral middle frontal, left pars triangularis, right entorhinal, and left cuneus corticies in the PTSD relative to the HC group, R2 = .69. Within the PTSD group, pre- to posttreatment symptom improvement was modeled by longitudinal decreases in the left posterior cingulate cortex, R2 = .45, and predicted by baseline measures of a smaller right isthmus (retrosplenial) cingulate and larger left caudate, R2 = .77. In sum, treatment was associated with longitudinal changes in brain regions that support executive functioning but not those that discriminated PTSD from HC participants at baseline. Additionally, results confirm a role for the posterior/retrosplenial cingulate as a correlate of PTSD symptom improvement and predictor of treatment outcome.

Loving-Kindness Meditation vs Cognitive Processing Therapy for Posttraumatic Stress Disorder Among Veterans

Additional options are needed for treatment of posttraumatic stress disorder (PTSD) among veterans. To determine whether group loving-kindness meditation is noninferior to group cognitive processing therapy for treatment of PTSD. This randomized clinical noninferiority trial assessed PTSD and depression at baseline, posttreatment, and 3- and 6-month follow-up. Veterans were recruited from September 24, 2014, to February 5, 2018, from a large Veternas Affairs medical center in Seattle, Washington. A total of 184 veteran volunteers who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for PTSD were randomized. Data collection was completed November 28, 2018, and data analyses were conducted from December 10, 2018, to November 5, 2019. Each intervention comprised 12 weekly 90-minute group sessions. Loving-kindness meditation (n = 91) involves silent repetition of phrases intended to elicit feelings of kindness for oneself and others. Cognitive processing therapy (n = 93) combines cognitive restructuring with emotional processing of trauma-related content. Co-primary outcomes were change in PTSD and depression scores over 6-month follow-up, assessed by the Clinician-Administered PTSD Scale (CAPS-5; range, 0-80; higher is worse) and Patient-Reported Outcome Measurement Information System (PROMIS; reported as standardized T-score with mean [SD] of 50 [10] points; higher is worse) depression measures. Noninferiority margins were 5 points on the CAPS-5 and 4 points on the PROMIS depression measure. Among the 184 veterans (mean [SD] age, 57.1 [13.1] years; 153 men [83.2%]; 107 White participants [58.2%]) included in the study, 91 (49.5%) were randomized to the loving-kindness group, and 93 (50.5%) were randomized to the cognitive processing group. The mean (SD) baseline CAPS-5 score was 35.5 (11.8) and mean (SD) PROMIS depression score was 60.9 (7.9). A total of 121 veterans (66%) completed 6-month follow-up. At 6 months posttreatment, mean CAPS-5 scores were 28.02 (95% CI, 24.72-31.32) for cognitive processing therapy and 25.92 (95% CI, 22.62-29.23) for loving-kindness meditation (difference, 2.09; 95% CI, -2.59 to 6.78), and mean PROMIS depression scores were 61.22 (95% CI, 59.21-63.23) for cognitive processing therapy and 58.88 (95% CI, 56.86-60.91) for loving-kindness meditation (difference, 2.34; 95% CI, -0.52 to 5.19). In superiority analyses, there were no significant between-group differences in CAPS-5 scores, whereas for PROMIS depression scores, greater reductions were found for loving-kindness meditation vs cognitive processing therapy (for patients attending ≥6 visits, ≥4-point improvement was noted in 24 [39.3%] veterans receiving loving-kindness meditation vs 9 (18.0%) receiving cognitive processing therapy; P = .03). Among veterans with PTSD, loving-kindness meditation resulted in reductions in PTSD symptoms that were noninferior to group cognitive processing therapy. For both interventions, the magnitude of improvement in PTSD symptoms was modest. Change over time in depressive symptoms was greater for loving-kindness meditation than for cognitive processing therapy. Clinicaltrials.gov Identifier: NCT01962714.

Efficacy and Underlying Mechanism of Acupuncture in the Treatment of Posttraumatic Stress Disorder: A Systematic Review of Animal Studies.

Acupuncture is a nonpharmacological intervention that can be useful in the clinical management of posttraumatic stress disorder (PTSD), especially in situations with a lack of medical resources, including large-scale PTSD events such as disasters. Some clinical studies have reported the clinical effect of acupuncture in improving PTSD symptoms, but the underlying therapeutic mechanism has yet to be explored. Therefore, this review summarized the underlying therapeutic mechanisms of acupuncture in animal PTSD models. A comprehensive search was conducted in 14 electronic databases, and two independent researchers performed study selection, data extraction, and the methodological quality assessment. Twenty-four relevant studies were included in this review and summarized according to the proposed main mechanisms. In behavioral evaluation, acupuncture, including manual acupuncture and electro-acupuncture, reduced anxiety and fear responses and weakened fear conditioning, improved sleep architecture, reduced depressive symptoms, and alleviated disturbance of spatial learning and memory of PTSD animal models. The therapeutic mechanisms of acupuncture proposed in the included studies could be classified into two categories: (1) regulation of stress responses in the neuroendocrine system and (2) promotion of neuroprotection, neurogenesis, and synaptic plasticity in several brain areas. However, the methodological quality of the included animal studies was not high enough to produce robust evidence. In addition, mechanistic studies on specific aspects of acupuncture that may affect PTSD, including expectancy effects, in human PTSD subjects are also needed.

Effectiveness of a rational emotive behavior therapy (REBT)-informed group for post-9/11 Veterans with posttraumatic stress disorder (PTSD)

ABSTRACT Various treatments aimed for posttraumatic stress disorder (PTSD) have been developed for Veterans, but many are not formatted for use in groups, do not address common psychiatric comorbidities, and include inherent barriers (e.g., substantial time commitment). This program evaluation study aimed to examine the effectiveness of a five-session treatment, a Rational Emotive Behavior Therapy (REBT)-Informed Group focused on changing irrational beliefs to address comorbid depression and anxiety (as well as anger and guilt) among post-9/11 Veterans with PTSD. Participants (n = 47) completing the REBT-Informed Group demonstrated significant reductions at posttreatment in depression and PTSD symptoms. Compared to Veterans in a ten-session treatment-as-usual group (n = 47), there was no significant difference in PTSD symptom improvement despite the reduction in number of sessions. The study demonstrates that a five-week group treatment for PTSD comorbid with depression or anxiety in post-9/11 Veterans – a therapy that may be uniquely suited to a military or Veteran population, but potentially generalizable to civilians as well – can lead to significant reductions in depression and PTSD symptoms. Future directions include development of a manual for dissemination and replication of findings of the REBT-Informed Group to other military or Veterans Affairs medical centers.

Trauma after the Gift of Life: Identification and Treatment of Post-Traumatic Stress Disorders in Heart Transplant Recipients

Introduction Orthotopic heart transplantation (OHT) recipients have rates of post-traumatic stress disorder (PTSD) over double that of the general population. PTSD after OHT is associated with increased mortality. Use of eye movement desensitization and reprocessing (EMDR) therapy is a novel treatment strategy for PTSD and recently shown to be more effective than cognitive behavioral therapy (CBT). EMDR after OHT has not been reported in the literature. We present two cases that highlight successful use of EMDR therapy post-OHT with improvement of PTSD symptoms. Case Report A 31-year-old female with non-compaction cardiomyopathy occurring during the post-partum period underwent OHT 6 weeks after delivery. Post-OHT course was uncomplicated with no episodes of rejection. Patient treated for depression with sertraline during first year post-OHT. Patient reported symptoms of PTSD with decreased functional capacity. Patient referred for consideration of EMDR therapy, found to be appropriate candidate by psychologist and underwent EMDR. Psychologist reported that patient experienced complete reduction in distress for targets. Patient reported resolution of PTSD symptoms and improved functional capacity. A 52-year-old male with hypertrophic cardiomyopathy underwent OHT, then required second OHT 5 years later due to graft dysfunction from progressive coronary vasculopathy. Course after re-OHT was notable for persistent, moderate cellular rejection requiring treatment with thymoglobulin, increase in baseline oral immunosuppression, and eventual addition of methotrexate. Patient treated for chronic, stable depression with sertraline and CBT. Patient reported symptoms of PTSD, specifically noting fear of needing a third transplant. Patient referred for consideration of EMDR therapy, found to be appropriate candidate by psychologist and underwent EMDR. Psychologist reported patient experienced significant but incomplete reductions in distress for targets and did not complete all sessions of EMDR therapy due to difficulties in the therapy. Patient reported improvement, but not resolution, of his PTSD symptoms. Summary Increased mortality is associated with PTSD after OHT. Therefore, OHT recipients experiencing PTSD symptoms should be referred for further evaluation. Additionally, the use of EMDR therapy could be considered.

The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial.

There is a pressing need for development of novel pharmacology for the treatment of Posttraumatic Stress Disorder (PTSD). Given increasing use of medical cannabis among US military veterans to self-treat PTSD, there is strong public interest in whether cannabis may be a safe and effective treatment for PTSD. The aim of the present study was to collect preliminary data on the safety and potential efficacy of three active concentrations of smoked cannabis (i.e., High THC = approximately 12% THC and < 0.05% CBD; High CBD = 11% CBD and 0.50% THC; THC+CBD = approximately 7.9% THC and 8.1% CBD, and placebo = < 0.03% THC and < 0.01% CBD) compared to placebo in the treatment of PTSD among military veterans. The study used a double-blind, cross-over design, where participants were randomly assigned to receive three weeks of either active treatment or placebo in Stage 1 (N = 80), and then were re-randomized after a 2-week washout period to receive one of the other three active treatments in Stage 2 (N = 74). The primary outcome measure was change in PTSD symptom severity from baseline to end of treatment in Stage 1. The study did not find a significant difference in change in PTSD symptom severity between the active cannabis concentrations and placebo by the end of Stage 1. All three active concentrations of smoked cannabis were generally well tolerated. The present study is the first randomized placebo-controlled trial of smoked cannabis for PTSD. All treatment groups, including placebo, showed good tolerability and significant improvements in PTSD symptoms during three weeks of treatment, but no active treatment statistically outperformed placebo in this brief, preliminary trial. Additional well-controlled and adequately powered studies with cannabis suitable for FDA drug development are needed to determine whether smoked cannabis improves symptoms of PTSD. Identifier: NCT02759185; ClinicalTrials.gov.

Low-dose clonidine in veterans with Posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) symptoms of hyperarousal are mediated through sympathetic nervous system hyperactivity. PTSD symptoms, including distressing thoughts and memories, flashbacks, hyperarousal, and sleep disturbances, have been linked with elevated norepinephrine levels in the cerebrospinal fluid. Clonidine, an alpha2-adrenergic agonist, reduces the release of norepinephrine and has been suggested as a treatment for PTSD. However, literature for use of clonidine in PTSD is limited. The objective of this study was to evaluate clinical records of patients with PTSD treated with clonidine to assess reported efficacy and safety. A cohort of veterans with PTSD treated with clonidine at a midwestern VA hospital between July 2015 and January 2018 were studied retrospectively. Medical records of 79 patients with moderate to severe PTSD symptoms were reviewed by three independent clinicians using the Clinical Global Impressions (CGI) scale to quantify symptom severity (CGI-S) before starting clonidine and subjects’ change in symptoms (CGI-I) after starting clonidine. Data on adverse events were also collected. Subgroup analyses were conducted on the impact of comorbid diagnoses, concurrent medications, and substance use. Mean CGI-S score at baseline was 4.8 (5 = markedly ill). After treatment with low-dose clonidine, 72% of patients experienced improvement, and 49% scored “much improved” or “very much improved.” Adverse effects were reported by 18 out of 79 subjects. In this retrospective analysis of veterans prescribed clonidine for PTSD, CGI-I scores suggested improvement in PTSD symptoms, and minimal side effects were reported. In addition, some comorbid diagnoses and concurrent medications were correlated with variations in outcomes.

Comparative efficacy and acceptability of expressive writing treatments compared with psychotherapy, other writing treatments, and waiting list control for adult trauma survivors: a systematic review and network meta-analysis.

Expressive writing about a traumatic event is promising in treating posttraumatic stress disorder (PTSD) symptoms in adult trauma survivors. To date, the comparative efficacy and acceptability of this approach is uncertain. Therefore, we aimed to examine the comparative efficacy and acceptability of expressive writing treatments. We included 44 RCTs with 7724 participants contributing 54 direct comparisons between expressive writing (EW), enhanced writing (i.e. including additional therapist contact or individualized writing assignments; EW+), PTSD psychotherapies (PT), neutral writing (NW), and waiting-list control (WL). EW, EW+, PT, and NW were statistically significantly more efficacious than WL at the longest available follow-up, with SMDs (95% CI) of -0.78 (-1.10 to -0.46) for PT, -0.81 (-1.02 to -0.61) for EW+ , -0.43 (-0.65 to -0.21) for EW, and -0.37 (-0.61 to -0.14) for NW. We found small to moderate differences between the active treatments. At baseline mean PTSD severity was significantly lower in EW+ compared with WL. We found considerable heterogeneity and inconsistency and we found elevated risk of bias in at least one of the bias dimensions in all studies. When EW+-WL comparisons were excluded from the analyses EW+ was no longer superior compared with EW. The summarized evidence confirms that writing treatments may contribute to improving PTSD symptoms in medium to long-term. Methodological issues in the available evidence hamper definite conclusions regarding the comparative efficacy and acceptability of writing treatments. Adequately sized comparative randomized controlled trials preferably including all four active treatment approaches, reporting long-term data, and including researchers with balanced preferences are needed.

The Effects of Modifying Dysfunctional Appraisals in Posttraumatic Stress Disorder Using a Form of Cognitive Bias Modification: Results of a Randomized Controlled Trial in an Inpatient Setting

Introduction: Dysfunctional appraisals about traumatic events and their sequelae are a key mechanism in posttraumatic stress disorder (PTSD). Experimental studies have shown that a computerized cognitive training, cognitive bias modification for appraisals (CBM-APP), can modify dysfunctional appraisals and reduce analogue trauma symptoms amongst healthy and subclinical volunteers. Objective: We aimed to test whether CBM-APP could reduce dysfunctional appraisals related to trauma reactions in PTSD patients, and whether this would lead to improvements in PTSD symptoms. Methods: We compared CBM-APP to sham training in a parallel-arm proof-of-principle double-blind randomized controlled trial amongst 80 PTSD patients admitted to an inpatient clinic. Both arms comprised a training schedule of 8 sessions over a 2-week period and were completed as an adjunct to the standard treatment programme. Results: In intention-to-treat analyses, participants receiving CBM-APP showed a greater reduction in dysfunctional appraisals on a scenario task from pre- to posttraining (primary outcome) assessments, compared to those receiving sham training (d = 1.30, 95% CI 0.82–1.80), with between-group differences also found on the Posttraumatic Cognitions Inventory (PTCI; d = 0.92, 95% CI 0.46–1.39) and the PTSD Checklist for DSM-5 (PCL-5; d = 0.63, 95% CI 0.18–1.08), but not for long-term cortisol concentrations (d = 0.25, 95% CI –0.28 to 0.78). Reductions in dysfunctional appraisals assessed via the scenario task correlated with reductions on the PTCI, PCL-5, and hair cortisol concentrations from pre- to posttraining time points. Conclusions: Results support dysfunctional appraisals as a modifiable cognitive mechanism, and that their proximal modification transfers to downstream PTSD symptoms. These findings could open new avenues for improving present therapeutic approaches.