A Randomized Clinical Trial of Quetiapine to Reduce Post-Concussive Syndrome Polypharmacy
Abstract
An unprecedentedly high number of mild traumatic brain injuries (mTBIs) were survived by combat Veterans who deployed in support of conflicts following 9/11 and thus became known as one of the signature injuries of modern combat. Combat-related mTBI is frequently associated with a concurrent psychological comorbidity, including post-traumatic stress disorder (PTSD) and high levels of disability and health care service utilization as long-term physical, psychological, and cognitive consequences in Veterans. Unfortunately, there are no FDA-approved or otherwise established medications or strong recommendations in the DOD/VA clinical practice guidelines for pharmacologic treatment of post-concussive symptoms. This lack of evidence to guide care often results in the use of multiple central nervous system-acting medications in the attempt to provide symptomatic relief for post-concussive symptoms and comorbid psychological conditions – resulting in polypharmacy practices which lead to adverse outcomes. Unfortunately, even this polypharmacy practice often fails to provide adequate symptom relief for either post-concussive symptoms or psychological comorbidity and adds undesired side effects to the burden of Veterans. Therefore, a huge need in the field of mTBI research is to find a single effective medication that reduces the burden of post-concussive symptoms without adding to the burden of Veterans through polypharmacy. Quetiapine, an atypical antipsychotic approved by the FDA, has a broad spectrum of actions at several receptors. Quetiapine’s ability to reduce irritability and anxiety and improve sleep without impairing sleep architecture is a distinct benefit over other medications and theoretically may benefit patients with post-concussive symptoms. Though quetiapine does have risks and side effects as an atypical antipsychotic, none of these prevent its effective use in short-term treatment for mTBI rehabilitation. Compared to other anti-psychotics, quetiapine has less risk of extra-pyramidal symptoms. Also, the risks for diabetes and heart disease are dose related effects on metabolic dysregulation that are associated with the high doses used to treat psychotic disorders. However, thorough medical screening for metabolic risk factors coupled with low- moderate quetiapine doses use can prevent any of these complications. Furthermore, starting a low dose scheduled at bedtime and slowly titrating up to a desired level of sedation may regularize the circadian rhythm and greatly improve sleep without interfering with the sleep. Both the psychopharmacological rationale, available safety data, and preliminary findings from our group, strongly argue for the need of a larger-scale phase 3 randomized clinical trial to determine the effectiveness of quetiapine monotherapy. We propose the need for a randomized pragmatic trial evaluating the efficacy of quetiapine in Veterans with co-morbid mTBI and PTSD specifically as an adjunct to comprehensive rehabilitation services delivered as a standard of care. Herein, we propose a randomized, pragmatic, open-label trial evaluating the efficacy of quetiapine monotherapy compared to TAU polypharmacy, as an adjunct to standard of care rehabilitation services in Veterans with mTBI and comorbid posttraumatic stress symptoms. The proposed project addresses the Treat Focus Area for a Level 2 CTA under the TBIPHRP BAA. Veterans (N=146) from South Texas Veterans Healthcare System and New Mexico VA Healthcare System. with PTS symptoms following an mTBI who are not currently using quetiapine will be enrolled in a phase 3, two-site, 16-week, randomized open-label pragmatic trial of quetiapine monotherapy vs. TAU polypharmacy as an adjunct to standard of care outpatient rehabilitation treatment. TAU Participants will continue their standard care prescribed medication adjusted to maximize benefits and minimize risk. Participants in the quetiapine group will be cross-tapered off ot
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310829
Entities
People
- Muhammad Baig
Organizations
- United States Army