Quetiapine for Post-Concussion Syndrome

Recruiting at 1 trial location

Overseen By Lizette Aviles, BS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Foundation for Advancing Veterans' Health Research

Must be taking: CNS active psychotropics

Must not be taking: Antipsychotics

Disqualifiers: Moderate TBI, Schizophrenia, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

146 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests quetiapine (also known as Seroquel or Seroquel XR) to determine its effectiveness for veterans with mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) symptoms. Researchers aim to compare quetiapine's effectiveness to the usual medications veterans typically take. Veterans who have experienced mTBI for at least six months and currently take three or more medications for symptoms might be suitable candidates. The trial seeks to improve the quality of life for those facing the challenges of mTBI and PTSD. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potential new treatment options.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications, but you need to be stable on at least three CNS active psychotropic medications for over a month. You cannot be taking any antipsychotics or prohibited medications within the past month.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that quetiapine is generally well tolerated. In past studies, quetiapine did not cause serious side effects such as involuntary movements or major changes in blood tests, suggesting its safety for treatment. Although the FDA mainly approves quetiapine for conditions like schizophrenia and depression, researchers are also studying its potential to reduce irritability, anxiety, and sleep problems without affecting sleep patterns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for post-concussion syndrome?

Unlike standard treatments for post-concussion syndrome, which typically involve a combination of rest, pain relievers, and sometimes antidepressants, Quetiapine Fumarate is unique because it targets the condition's symptoms through a different mechanism. Quetiapine is an antipsychotic that works by balancing neurotransmitters in the brain, which could potentially address a broader range of symptoms such as mood swings and sleep disturbances. Researchers are excited about Quetiapine because it offers a new approach that might be more effective for patients who don't respond well to the usual care, potentially improving their quality of life faster and more comprehensively.

What evidence suggests that quetiapine might be an effective treatment for post-concussion syndrome?

Research has shown that quetiapine may help individuals with mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD). One study found that quetiapine can reduce irritability, anxiety, and sleep problems, which often occur after a concussion. In a small pilot study, participants with brain injuries were less aggressive and irritable when taking quetiapine. In this trial, participants will either receive quetiapine, cross-tapered up to a maximum dose of 200 mg, or continue with Treatment As Usual (TAU). These findings suggest that quetiapine might alleviate certain symptoms of post-concussion syndrome. However, more research is needed to fully understand its benefits for this condition. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for veterans aged 18-65 with mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD), who have been stable on at least three CNS psychotropic medications for over a month. Participants must have PTSD symptoms and report post-concussion syndrome (PCS) symptoms, with the mTBI occurring at least six months prior to screening.

Inclusion Criteria

I am a veteran aged 18-65 seeking treatment for a mild traumatic brain injury.

I have had a mild traumatic brain injury and still experience symptoms after six months.

I've been on a stable dose of 3 or more psychiatric meds for over a month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive quetiapine monotherapy or Treatment As Usual (TAU) for managing symptoms of mTBI and PTSD

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Quetiapine Fumarate

Trial Overview The study compares quetiapine monotherapy—a medication that can affect neurotransmitters in the brain—to standard treatment as usual (TAU). It's designed to see if quetiapine is more effective in managing symptoms of mTBI and PTSD in veterans undergoing rehabilitation therapy.

How Is the Trial Designed?

Group I: Quetiapine Experimental Treatment 1 Intervention

Quetiapine will be cross-tapered up to a maximum dose of 200 mg (as tolerated) as other standard of care medications are discontinued.

Group II: Treatment As Usual (TAU) Active Control 1 Intervention

Participants in the TAU group will have doses adjusted over the same period as indicated by usual care criteria.

Quetiapine Fumarate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Seroquel for:

• Schizophrenia
• Bipolar disorder
• Major depressive disorder

Approved in European Union as Seroquel for:

• Schizophrenia
• Bipolar disorder
• Major depressive disorder

Approved in Canada as Seroquel for:

• Schizophrenia
• Bipolar disorder
• Major depressive disorder

Who Is Running the Clinical Trial?

Foundation for Advancing Veterans' Health Research

Lead Sponsor

Trials

3

Recruited

330+

The University of Texas Health Science Center at San Antonio

Collaborator

Trials

486

Recruited

92,500+

Biomedical Research Institute of New Mexico

Collaborator

Trials

11

Recruited

2,300+

Published Research Related to This Trial

In a study involving 286 patients with schizophrenia, high-dose quetiapine (up to 750 mg/d) significantly reduced positive symptoms compared to placebo, demonstrating its efficacy as an antipsychotic.

Quetiapine was well tolerated, showing a favorable safety profile without causing extrapyramidal symptoms or significant changes in blood parameters, suggesting it is a safe treatment option for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group. Small, JG., Hirsch, SR., Arvanitis, LA., et al.[2022]

In a 6-week pilot study involving 7 participants with aggression due to traumatic brain injury, quetiapine was found to be effective in reducing irritability and aggression.

Quetiapine was well-tolerated at doses ranging from 25 to 300 mg daily, and its use was associated with improvements in cognitive functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of quetiapine treatment of aggression due to traumatic brain injury. Kim, E., Bijlani, M.[2019]

Quetiapine fumarate effectively reduced symptoms of schizophrenia in animal models, showing significant improvement in both negative and positive symptoms when tested against phencyclidine and amphetamine.

The study indicated that quetiapine fumarate has a lower risk of inducing extrapyramidal side effects compared to other antipsychotics, as evidenced by its minimal impact on forelimb retraction time in the paw test.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atypical antipsychotic effects of quetiapine fumarate in animal models. Guan, HJ., Dai, J., Zhu, XZ.[2013]

In a 12-week study involving 20 patients (10 with bipolar disorder and 10 with schizoaffective disorder), quetiapine significantly improved symptoms as measured by the Brief Psychiatric Rating Scale, Young Mania Rating Scale, and Hamilton Rating Scale for Depression, indicating its efficacy in treating these mood disorders.

Quetiapine was well tolerated, with a mean dose of 202.9 mg/day and a reported average weight gain of 10.9 lbs, suggesting that while effective, monitoring for weight changes is important during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine alone and added to a mood stabilizer for serious mood disorders. Sajatovic, M., Brescan, DW., Perez, DE., et al.[2019]

In a 6-week study involving 119 Chinese Han patients with schizophrenia, quetiapine (750 mg/day) showed comparable efficacy to risperidone (4 mg/day) in improving symptoms, with no significant differences in overall treatment outcomes.

Quetiapine had a significantly lower rate of extrapyramidal symptoms and hyperprolactinemia compared to risperidone (13.3% vs. 43.3%), although dizziness was more common in the quetiapine group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of quetiapine and risperidone in Chinese Han patients with schizophrenia: results of a single-blind, randomized study. Li, Y., Li, H., Liu, Y., et al.[2022]

In a study involving 10 adolescents aged 12.3 to 15.9 years with chronic or intermittent psychotic disorders, quetiapine fumarate was found to be well tolerated, with no unexpected side effects and no serious adverse events reported.

Quetiapine effectively improved both positive and negative symptoms of psychosis, as evidenced by significant reductions in various psychiatric rating scales, indicating its potential as a safe treatment option for adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders. McConville, BJ., Arvanitis, LA., Thyrum, PT., et al.[2019]

In a 16-week trial involving 6 boys with autistic disorder, quetiapine fumarate showed no significant overall improvement in symptoms, with only 2 subjects considered responders by the end of the study.

The treatment was poorly tolerated, leading to significant side effects such as sedation, behavioral activation, increased appetite, and weight gain, which caused several participants to drop out before completing the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label quetiapine in the treatment of children and adolescents with autistic disorder. Martin, A., Koenig, K., Scahill, L., et al.[2015]

A case report of a patient with schizophrenia who suffered a traumatic brain injury showed that treatment with quetiapine led to significant recovery, allowing him to be discharged to a rehabilitation unit.

Quetiapine may have neuroprotective effects by reducing blood-brain barrier permeability and promoting neurogenesis, suggesting its potential role in treating neurological deficits following traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of quetiapine in protection of neurodegeneration after traumatic brain injury. Morra, JA., Alao, AO.[2020]

Quetiapine fumarate ('Seroquel') is an atypical antipsychotic that has shown promise in treating schizophrenia, particularly in patients with therapy-resistant forms of the disorder, as demonstrated in a case study of a 58-year-old man treated successfully for 5 years.

This medication has a unique mechanism of action, with a greater affinity for serotonin receptors and a lower risk of causing extrapyramidal symptoms or increasing prolactin levels, which may improve patient compliance and overall treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of quetiapine in treatment-refractory schizophrenia: A case report. Reznik R Benatov P Sirota, I.[2014]

Quetiapine fumarate is effective and well-tolerated for treating schizophrenia, making it suitable for initial treatment or for patients needing to switch from other antipsychotics due to side effects.

The recommended titration schedule for quetiapine starts at 50 mg and increases to 400 mg over five days, with effective maintenance doses ranging from 150 to 750 mg per day, allowing for individualized treatment with minimal risk of relapse or withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosing and switching strategies for quetiapine fumarate. Cutler, AJ., Goldstein, JM., Tumas, JA.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06333990?cond=%22Traumatic%20Brain%20Injury%22&intr=%22Antipsychotic%20Agents%22&viewType=Table&rank=1

Quetiapine to Reduce Post Concussive Syndrome After ... A two site, 2-arm, Phase III randomized pragmatic clinical trial evaluating the effectiveness of quetiapine monotherapy in comparison to Treatment As Usual (TAU) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7545554/

Quetiapine augmentation of prolonged exposure therapy in ... Quetiapine attenuates irritability, anxiety and sleep disturbances without impairing sleep architecture, [63] and theoretically may benefit ...

3. withpower.com withpower.com/trial/phase-3-brain-injuries-3-2024-a4356

Quetiapine for Post-Concussion Syndrome In a 6-week pilot study involving 7 participants with aggression due to traumatic brain injury, quetiapine was found to be effective in reducing irritability ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33032657/

Quetiapine augmentation of prolonged exposure therapy in ... This randomized, open-label study was designed to evaluate the feasibility of completing a randomized trial of quetiapine vs. treatment as usual to promote ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06333990/quetiapine-to-reduce-post-concussive-syndrome-after-mild-traumatic-brain-injury-mtbi

Quetiapine to Reduce Post Concussive Syndrome After ... A two site, 2-arm, Phase III randomized pragmatic clinical trial evaluating the effectiveness of quetiapine monotherapy in comparison to ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK459145/

Quetiapine - StatPearls - NCBI Bookshelf - NIH Quetiapine is FDA approved for schizophrenia, acute manic episodes, and adjunctive treatment for major depressive disorder.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00326144

NCT00326144 | Efficacy and Safety of Quetiapine ... The purpose of this study is to demonstrate superior efficacy of Quetiapine fumarate sustained release (SEROQUEL) compared with placebo when used as a mono- ...