Written Exposure Therapy Plus Adjunctive Methylphenidate Treatment for Veterans With PTSD

There is a critical need for novel, and efficacious treatment strategies for post-traumatic stress disorder (PTSD) in Veterans. Gold standard treatments at the VA include evidence-based therapies that leverage fear extinction mechanisms such as Prolonged Exposure and Written Exposure Therapy (WET). Although these treatments are effective, \~50% of Veterans do not show remission after treatment, indicating efforts to further enhance treatment efficacy are critical. Preclinical, translational, and clinical studies support the potential success of using methylphenidate (MPH; Ritalin) to improve PTSD symptoms and augment fear extinction. However, methylphenidate (MPH) has not been tested as an adjunctive treatment for exposure-based therapy (or any therapy) in those with PTSD. This project aims to (1) conduct a Phase 2a randomized controlled trial (RCT) of MPH to assess initial safety, tolerability, and potential to enhance efficacy of Written Exposure Therapy, and (2) to identify physiological and behavioral markers of treatment response. If successful, this work will provide clinically actionable information on the feasibility and efficacy of a scalable, mechanism-informed enhancement to behavioral therapies for PTSD in Veterans, supporting more efficient VA care delivery, precision medicine approaches, and improved clinical outcomes. This study evaluates the efficacy of WET plus MPH (WET+MPH) versus WET plus placebo (WET+PBO) to treat Veterans with PTSD. Specifically, this design tests the ability of serial, acute, pre-session doses of 40mg of MPH, relative to PBO, to augment PTSD symptom recovery in the context of Written Exposure Therapy, using a double-blind, placebo-controlled, randomized controlled trial design in n=138 Veterans. The primary objective is to assess PTSD symptom reduction, hypothesizing superior outcomes with WET+MPH. Additional aims examine safety and tolerability of WET+MPH and psychophysiological markers of fear extinction learning. The investigators expect that measures of safety and tolerability will be comparable across groups, and that WET+MPH will enhance extinction learning compared to WET+PBO. This study will advance our mechanistic understanding of therapeutic change by incorporating validated clinical, behavioral, and physiological assessments to enable precise characterization of how MPH alters learning processes central to PTSD recovery.