A Randomized Clinical Trial of Quetiapine Monotherapy vs. Treatment as Usual Polypharmacy for Postconcussive Syndrome in Veterans

Apr 15, 2024

Mild traumatic brain injury (mTBI) is a signature wound of post-9/11 wars, affecting hundreds of thousands of military veterans. After surviving the injury, many may continue to struggle not only with a variety of postconcussive symptoms, but also with the side effects of the multiple medications typically used to treat them.

With no FDA-approved therapies for postconcussive syndrome, treatment usually involves several prescriptions to treat various physical, neurological, and psychological symptoms as patients present with them. So one patient may be on a cocktail of medicines to help with headaches, concentration problems, neuropathic pain, fatigue, insomnia and anxiety. Each of those medications has its own side effects, most of which match other postconcussive and posttraumatic stress symptoms.

It’s easy to see, then, how patients can feel like nothing is helping, and doctors can have difficulty determining what’s working, what’s not, and how to make effective treatment adjustments.

Testing whether less is better

Seeing the problems of current polypharmacy approaches, STRONG STAR investigators are conducting a large randomized clinical trial (RCT) to evaluate the efficacy of using one medication – quetiapine – to treat a variety of postconcussive symptoms and improve patients’ function and quality of life. Quetiapine is an atypical antipsychotic medication that acts on multiple neurotransmitter receptors and therefore has the potential to help with multiple symptoms.

The study team is led by Muhammad Rais Baig, MD, with the Polytrauma Rehabilitation Center at the South Texas Veterans Health Care System and on the faculty at The University of Texas Health Science Center at San Antonio.

Dr. Baig previously led a pilot study evaluating quetiapine therapy compared to treatment as usual in veterans with posttraumatic stress disorder (PTSD), which frequently co-occurs in mTBI patients and has many symptoms in common. In that pilot study, quetiapine led to increased engagement in and completion of trauma-focused therapy. Importantly, it also resulted in overall improvement in both PTSD and mTBI symptoms.

Those findings led to the hope that quetiapine may be a useful monotherapy for those who have experienced mTBI, allowing providers to address multiple symptoms and patients to experience better outcomes with fewer negative side effects.

RCT design

In the current trial, 146 veterans with symptoms of mTBI and posttraumatic stress will be enrolled at the South Texas and the New Mexico VA Health Care Systems. Half will be randomly assigned to continue “treatment as usual” with their currently prescribed prescription medications. The other half will be assigned to the quetiapine arm. They will gradually reduce other prescribed medications for mTBI symptoms until they are taking quetiapine only.

At the end, investigators will examine whether quetiapine alone was more effective in reducing postconcussive symptoms and related functional disability, and whether it led to improved quality of life for participants.  They also will explore whether quetiapine monotherapy enhances mTBI recovery by reducing medication side effects and increasing engagement in other rehabilitation services.

Expected benefits

An evidence-based monotherapy could greatly improve the outcomes of veterans suffering from postconcussive symptoms following mTBI, as they could benefit from greater symptom reduction with fewer adverse side effects. This in turn could lead to their greater utilization of complementary rehabilitation services and even better outcomes. At the national level, positive findings from this study could be expected to influence the joint Department of Veterans Affairs/Department of Defense Clinical Practice Guidelines, minimize polypharmacy practices, and reduce the ongoing demands of an unremitted chronic condition affecting thousands of veterans.