A Phase 2 interventional study of Written Exposure Therapy (WET) and methylphenidate (MPH) in PTSD - Post Traumatic Stress Disorder, sponsored by VA Office of Research and Development. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-29.
Sponsored by VA Office of Research and Development · Phase 2, Interventional, and Treatment
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.
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.
147 studies on the registry are indexed under Combat Disorders; 76 are open to participants now.
This study's planned enrollment of 138 is above the median of 71 across 124 interventional studies indexed under Combat Disorders.
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Of its 212 completed or terminated interventional studies of FDA-regulated products, 185 (87%) have results posted.
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Exclusion Criteria:
Written Exposure Therapy plus methylphenidate (MPH 40mg)
Behavioral: Written Exposure Therapy (WET) · Drug: methylphenidate (MPH)
Written Exposure Therapy plus placebo (PBO)
Behavioral: Written Exposure Therapy (WET) · Drug: placebo (PBO)
WET will administered per manualized protocol, either in-person or via telehealth technology
active medication
Also known as: Ritalin
non-active medication
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Post-traumatic stress disorder (PTSD) symptom severity will be measured via the diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), where the CAPS-5 score range = 0 - 80. Higher scores = more severe PTSD symptoms.
Time frame: Change from pre-treatment to 4-weeks post-treatment
Adverse Event Checklist (AE Checklist)
The Adverse Event Checklist (AE Checklist) is a list of standard complaints that includes frequent side effects of methylphenidate. The AE Checklist will be used to guide evaluation of adverse events and to help determine AE occurrence, AE-related medication dose adjustments, AE-related medication discontinuation, or AE-related study withdrawal. Greater number of items endorsed = greater occurrence of adverse events.
Time frame: The Modified-FIBSER is collected at every WET session (sessions 1-5), over a timeframe of up to 10 weeks
Modified Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) Scale
Self-rated severity of within session side effects as measured by a Modified Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) Scale . The FIBSER scale is a self-report measure providing 3 global ratings of frequency, intensity, and burden to assess side effects of pharmacotherapy. The scale was modified to measure perceived within-session medication side-effects and the degree to which they interfere with Written Exposure Therapy session goals. The M-FIBSER will be used to guide evaluation of side effects and to help determine study medication tolerability. The M-FIBSER score has three items ranging 0 - 6. Higher scores = more severe frequent/severe/or burdensome side effects.
Time frame: The Modified-FIBSER is collected at every WET session (sessions 1-5), over a timeframe of up to 10 weeks
Fear Extinction learning
Fear potentiated startle is a behavioral indicator of conditioned fear responses, collected during extinction, measured using eyeblink electromyogram (EMG) response. Extinction learning (change in response to conditioned fear cue) as measured by EMG during extinction training session is the secondary outcome measure. EMG responses are measured as arbitrary digital units 0-4095 AU (0.5 mV input unit=2500 mV output unit).
Time frame: Change from pre-treatment to 4-weeks post-treatment
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Post-traumatic stress disorder (PTSD) symptom severity will be measured via the diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), where the CAPS-5 score range = 0 - 80. Higher scores = more severe PTSD symptoms.
Time frame: Change from pre-treatment to 20-weeks post-treatment
Plan to share: Yes — Upon completion of the study and no later than 6 months after breaking the blind the data will be uploaded to the VA CESAMH Biorepository. The VA CESAMH Biorepository will house the data for future analyses. Requests for data will be approved through the Biorepository Board and with appropriate Data Use Agreement across the VA and requesting institution. US-based academic and Veteran Affairs institutions may apply for data access.
Supporting information: Study protocol, Informed consent form
Time frame: VA CESAMH Biorepository has no time limits except the limitation on the repository life itself (\~99 years).
Access criteria: Data will be made available to the Biorepository no later than 6 months after study completion and blind has been broken. Once it is housed in the repository, VA Handbook 1200.12 repository guidelines will apply for approved data request and transfers.
No publications or documents are linked to this record.
Start is estimated for Jul 2027; primary completion for Sep 2030, 38 months later.
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Methylphenidate
VA Office of Research and Development →