Many Veterans with post-traumatic stress disorder (PTSD) do not fully benefit from the best current treatments, some of which focus on helping the brain regulate trauma memories. While therapies like Prolonged Exposure and Written Exposure Therapy work for many, about half of Veterans still struggle with symptoms even after treatment. Research suggests that methylphenidate (commonly known as Ritalin), a safe and widely used medication, may improve PTSD symptoms and related mechanisms. This project will test whether adding methylphenidate to Written Exposure Therapy will result in a greater reduction in PTSD symptoms compared to Written Exposure Therapy alone. The investigators will also study body and behavior markers to better understand how and why some Veterans respond to treatment. If successful, this approach could give providers a new, practical tool to improve recovery from PTSD. Ultimately, this work could lead to more personalized, effective care for Veterans, helping them return to fuller and healthier lives.
Enhancing Written Exposure Therapy in Veterans With Posttraumatic Stress: Clinical, Physiological and Behavioral Markers of Adjunctive Methylphenidate Treatment
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.