RECONSOLIDATION OF TRAUMATIC MEMORIES TO RESOLVE POSTTRAUMATIC STRESS DISORDER (RECONTROL PTSD)

Rationale: Since 2001, 2.7 million U.S. SMs have deployed to Iraq or Afghanistan: an estimated 13-20% have PTSD. Despite billions spent by DoD and VA on PTSD, serious comorbidities including suicide are common. Current treatments for PTSD are costly and may take months or years. Reconsolidation of Traumatic Memories (RTM) is a novel treatment that uses reconsolidation blockade to update long-term trauma memories. Reconsolidation includes: accessing and quickly terminating the target memory; introducing novel information relevant to the original memory during an ensuing 1-6 hour period of memory malleability; and retesting the reminder after ≥ 24 hours. RTM is a standardized protocol targeting traumatic memories primarily manifest in nightmares, flashbacks, and high reactivity. RTM activates the traumatic memory with a brief reminder, while the therapist monitors for signs of sympathetic arousal (e.g, flushing, facial expression, muscular tone, tearing). They interrupt the arousal, and intervene to facilitate return to a safe, present time orientation. We believe that this renders the memory malleable for several hours. Dissociative exercises change the salience of the memory on an unconscious level. Alterations of the memory may include: color, clarity, speed and direction, distance, perspective, and outright rescripting. This is all done in the context of an imaginal movie theater. The movie is imagined as a fast (~45 secs), black and white movie of the trauma memory. If at any point the participant expresses discomfort, they are reoriented and calmed to ensure the termination of overt sympathetic response; the current version of the movie is adjusted so that the patient can comfortably watch it, and the treatment continues. Recent waitlist RCTs of RTM report remission of PTSD in ≥ 65% of completers, with symptom reductions ~40 points (PSS-I and PCL-M). The stage is now set for a randomized, controlled, single-blind study comparing RTM directly with PE, the PTSD therapy with the strongest current evidence base.Hypotheses: 1) RTM will prove non-inferior to PE in reducing PTSD symptom severity (PSS-I score) at treatment completion and 1-year follow up. 2) Among treatment completers, RTM will achieve faster remission, with fewer dropouts, than PE. 3) Cognitive function (NIH toolbox) will significantly improve in successful treatment completers. 4) Epigenetic markers will correlate with treatment response.Research: We will randomize 108 active or retired SMs with PTSD to ≤10 sessions of RTM or PE, affording power to test our hypotheses while allowing for ≤ 25% dropouts. Using an Intent to treat analysis, missing data for untreated drop-outs will be imputed using Baseline Observation Carried Forward (BOCF). Scores for mid- treatment and post treatment drop-outs will be imputed using Last Observation Carried Forward (LOCF). The therapist-administered PSS-I will be the primary outcome measure, with secondary measures of depression (PHQ-9), anxiety (GAD-7), sleep (PSQI), and functional status (WHOQOL-100), pre- and post-treatment, and at 2, 6, and 12 months. The PSS will be completed before sessions 2, 4, 6, and 8 to assess speed of response. If the initial trauma is resolved, secondary trauma(s) may be treated, and treatment ended upon remission. ANOVA will compare symptom severity over time within and between groups. Blood draws will be obtained pre- and post-treatment to assess predictors of treatment response and epigenetic markers of change. The NIH Toolbox Neurocognitive Assessment, pre- and post-treatment, will assess the impact on cognitive function.Innovation and Impact: RTM is a brief, non-traumatizing treatment for PTSD reporting responses in ≤ 6 sessions. Prior waitlist-controlled RTM trials report a dropout rate of ~8% (vs. 20-50% for other treatments) and an effect size of at least 1.2, suggesting RTM is an efficient and palatable intervention improving PTSD enrollment, attrition, and response rates. This novel approach manipulates structural elements of target memories using behavioral cues (rather than pharmaceuticals, e.g.: propranolol, DCS) to induce memory labilization. We have previously documented how persistent symptoms and cognitive impairments-post-TBI-are strongly related to PTSD symptom severity. We will track comorbid TBI, anticipating it will not adversely impact response. More palatable and effective therapies for PTSD, with and without TBI, must be developed and evaluated. RTM is a safe and promising approach that requires testing against evidence-based interventions in well-designed RCTs. Demonstration of corresponding biomarkers and neurocognitive improvements will markedly enhance the significance of our results, potentially facilitating more tailored treatment approaches in the future, along with the promise of being able to target neurocognitive improvement in those with comorbid PTSD and TBI.