# Understanding CNS Stimulant Use and Safety in Veterans with TBI

> **NIH VA I01** · U.S. DEPT/VETS AFFAIRS MEDICAL CENTER · 2024 · —

## Abstract

Project Summary/Abstract
Background: The use of central nervous system (CNS) stimulants such as amphetamine, dextroamphetamine,
methylphenidate, armodafinil and modafinil is discouraged in patients with traumatic brain injury (TBI) as they
have no proven benefits and carries the FDA black-box warning of a higher risk for developing substance use
disorders (SUD).
Significance: TBI is a major source of morbidity and mortality for Veterans, and a top HA/ORD/HSR&D priority.
Our preliminary data suggest that as of May 2021, nationwide 728,065 Veterans had a diagnosis of TBI in their
EHR. The TBI registry estimates that 81% of the Veterans have mild TBI. Veterans with TBI are more likely to
receive CNS stimulants than those without TBI. Our preliminary data suggests that 5.8% (42,437/728,065) of
the Veterans with TBI received prescriptions for CNS stimulants, which is over 10 times higher than that in
Veterans without TBI (0.56%). Findings of our preliminary study also suggest that compared to non-users of
CNS stimulants, users have a higher risk of SUD. Currently, there is no evidence-based therapy for treatment of
mild TBI and the VA mild TBI guidelines discourages the use of medications to ameliorate neurocognitive
symptoms. However, many Veterans with TBI receive prescriptions for CNS stimulants but less is known about
the safety of these drugs in Veterans with TBI.
Innovation & Impact: To the best of our knowledge, the study questions have never been answered before.
The key innovation of the proposed study is in the filling of the scientific knowledge gap, the potential clinical
implications of the findings, and the relevance to the Veteran population. Our methodological innovation will
include the use of deep machine learning approaches including the impact and the interaction scores developed
by our team to quantify the results of deep learning.
Specific Aims: 1) To characterize stimulant prescription pattern in Veterans with mild TBI; 2) To test the
hypothesis that initiation of stimulant therapy is associated with a higher risk of incident SUD, hospitalization,
and mortality in Veterans with mild TBI; and 3) To develop an explainable machine (deep) learning risk prediction
model that will allow a more accurate and precise assessment of clinical benefits vs. risk of stimulants in
individual Veterans.
Methodology: These aims will be achieved by using the VA TBI registry and EHR data. For Aims 1 and 3, we
will use all Veterans with a TBI diagnosis and any use of stimulants. For Aim 2, we will emulate the design of an
RCT, using Veterans with TBI free of prevalent SUD and new prescriptions of CNS stimulants after mild TBI
diagnosis. We will then conduct sensitivity analysis in the subset of Veterans with mild TBI using the
Comprehensive TBI Evaluation (CTBIE) tables. Propensity score matching will be used for outcome-blinded
assembly of cohorts balanced on measured covariates, and sensitivity analyses will be used to estimate impact
of unmeasured...

## Key facts

- **NIH application ID:** 10848181
- **Project number:** 5I01HX003552-02
- **Recipient organization:** U.S. DEPT/VETS AFFAIRS MEDICAL CENTER
- **Principal Investigator:** ALI AHMED
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848181

## Citation

> US National Institutes of Health, RePORTER application 10848181, Understanding CNS Stimulant Use and Safety in Veterans with TBI (5I01HX003552-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10848181. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*