Search

Background: The 2023 VA/DoD Clinical Practice Guideline for the Management of PTSD recommends individual, manualized trauma-focused such as Prolonged Exposure (PE) over pharmacologic interventions for the primary treatment of PTSD. Unfortunately, clinical trials of trauma-based therapies in the military and veteran population showed that 30% to 50% of patients did not demonstrate clinically meaningful symptom change. Ketamine, an FDA-approved anesthetic with potent non-competitive glutamatergic N-methyl-d-aspartate antagonistic properties, has demonstrated to enhance the recall of extinction learning and decrease fear renewal without interference of extinction training in preclinical studies., Methods: We plan to conduct a single site RCT comparing three ketamine treatment vs. active placebo (midazolam) adjunct to PE therapy among Veterans with PTSD. Pharmacological phase will start simultaneously with PE session 1. Infusions will be administered 24 h. prior to PE session for the first 3 weeks. After PE is completed (session 10), patients will be assessed during a 3-month follow-up period at various time points. We estimate that out of 100 veterans, 80 will reach time point for primary outcome measure and will be considered for primary analysis. Secondary outcomes include severity of depression and anxiety scores, safety and tolerability of ketamine-enhanced PE therapy, cognitive performance during treatment and early improvement during PE related to the rate of dropouts during PE therapy., Discussion: Results of the proposed RCT could provide scientific foundation to distinguish the essential components of this approach, enhance the methodology, elucidate the mechanisms involved, and identify sub-PTSD populations that most likely benefit from this intervention., Competing Interests: Declaration of competing interest The authors report no financial relationships with commercial interests., (Published by Elsevier Inc.)

The STRONG STAR Consortium (South Texas Research Organizational Network Guiding Studies on Trauma and Resilience) and the Consortium to Alleviate PTSD are interdisciplinary and multi-institutional research consortia focused on the detection, diagnosis, prevention, and treatment of combat-related posttraumatic stress disorder (PTSD) and comorbid conditions in military personnel and veterans. This manuscript outlines the consortia's state-of-the-science collaborative research model and how this can be used as a roadmap for future trauma-related research. STRONG STAR was initially funded for 5 years in 2008 by the U.S. Department of Defense's (DoD) Psychological Health and Traumatic Brain Injury Research Program. Since the initial funding of STRONG STAR, almost 50 additional peer-reviewed STRONG STAR-affiliated projects have been funded through the DoD, the U.S. Department of Veterans Affairs (VA), the National Institutes of Health, and private organizations. In 2013, STRONG STAR investigators partnered with the VA's National Center for PTSD and were selected for joint DoD/VA funding to establish the Consortium to Alleviate PTSD. STRONG STAR and the Consortium to Alleviate PTSD have assembled a critical mass of investigators and institutions with the synergy required to make major scientific and public health advances in the prevention and treatment of combat PTSD and related conditions. This manuscript provides an overview of the establishment of these two research consortia, including their history, vision, mission, goals, and accomplishments. Comprehensive tables provide descriptions of over 70 projects supported by the consortia. Examples are provided of collaborations among over 50 worldwide academic research institutions and over 150 investigators., (Published by Elsevier Inc.)

Objective: Age at onset of first major depressive episode (MDE) does not necessarily translate into different treatment outcomes to antidepressants in late-life depression. The influence of genetic variants may affect this relationship., Design: Post hoc data set analysis of the association between variants in the promoter region (indel, rs25531) and within intron 2 (Stin2 VNTR) of the SCL6A4 gene and treatment outcomes among older participants in the first treatment arm of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D)., Setting: Participants were enrolled from 23 psychiatric and 18 primary care settings., Participants: Two hundred twenty-one, white non-Hispanic subjects, aged 60 to 75 years, with 16-item Quick Inventory of Depressive Symptomatology-Clinician Rating (QIDS-CR16) initial score ≥10, and who remained in the study for at least 6 weeks, were genotyped., Intervention: Citalopram treatment for up to 14 weeks., Measurements: Main outcome was remission rate defined as a score of ≤5 on the QIDS-CR16. Response was a secondary outcome defined as a reduction of ≥50% of baseline QIDS-CR16., Results: Polymorphism in the indel promoter region was associated with remission among subjects whose first lifetime episode of major depression occurred later than age 55. In this group, subjects with L/L genotype had significantly higher remission (80% versus 43%) compared to those subjects with any other indel promoter genotype. Multivariate analysis demonstrated that the genetic effect of the indel promoter region on remission increases along with age at onset of MDE., Conclusions: Variants in the indel promoter region of the SLC6A4 gene have a more robust effect to antidepressant outcome among older subjects who experienced their first MDE at a later age. The mechanism of action of these variants remains to be determined., (Published by Elsevier Inc.)