Buspirone for Traumatic Brain Injury Irritability and Aggression

Overseen By Flora Hammond, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Indiana University

Must not be taking: Buspirone

Disqualifiers: Schizophrenia, Psychosis, Neurologic disease, others

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: 5

Duration: 13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if buspirone, an anti-anxiety medication, can help manage irritability and aggression after a traumatic brain injury. Participants will receive either buspirone or a placebo to compare effects. Individuals with a closed head injury (a brain injury without an object penetrating the skull) for at least six months who are experiencing new or worsened irritability may qualify. An observer, such as a family member or close friend, must also report on the participant's behavior. As a Phase 4 trial, this research explores how an FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications, but it requires no changes in your medications during the month before and throughout the 91-day trial period.

What is the safety track record for Buspirone?

Research has shown that buspirone is safe and generally well-tolerated for treating various conditions. The FDA has already approved this medication for anxiety disorders, so its safety is well-documented. Studies have also found that buspirone can help with symptoms like irritability and aggression after a traumatic brain injury.

In past research, buspirone improved behavior in people with brain injuries and caused few side effects. Participants in these studies reported only minor issues, suggesting buspirone is generally safe. Most side effects, such as dizziness or headaches, were mild. This suggests buspirone might be a good option for those dealing with behavior problems after an injury. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Buspirone is unique because it targets irritability and aggression in patients with traumatic brain injury (TBI) through a mechanism that differs from the standard of care, which often includes medications like antipsychotics or mood stabilizers. Unlike those treatments, buspirone acts on the serotonin receptors, which may lead to fewer side effects and a better safety profile. Researchers are excited about buspirone's potential to provide a more targeted and tolerable option for managing TBI-related behavioral issues.

What evidence suggests that Buspirone might be an effective treatment for post-TBI irritability and aggression?

Research has shown that buspirone, which participants in this trial may receive, can reduce irritability and aggression in individuals with traumatic brain injury (TBI). One study found that 60% of patients experienced a 50% reduction in aggressive symptoms. Another study reported that 90% of patients exhibited improved behavior after taking buspirone for at least three months. Buspirone has also proven effective in treating aggression related to other conditions, such as intellectual disabilities and dementia. This suggests that buspirone might help manage similar symptoms in people with TBI. ^{1 6 7 8 9}

Who Is on the Research Team?

Flora Hammond, MD

Principal Investigator

Indiana University/Rehabilitation Hospital of Indiana

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with traumatic brain injury (TBI) who have experienced increased irritability or aggression since their injury, which occurred at least 6 months prior. Participants must not plan any medication changes during the study and need a reliable observer to report on their behavior.

Inclusion Criteria

Vision, hearing, speech, motor function, and comprehension sufficient for compliance with all testing procedures and assessments

Voluntary informed consent of patient and observer

Observer-rated NPI Irritability Domain score 6 or greater to include only moderate-severe irritability

Exclusion Criteria

History of schizophrenia or psychosis

I have taken buspirone in the last month.

I am showing signs of an active infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either buspirone or placebo, with 4 clinic visits for assessments

13 weeks

4 visits (in-person)

Continuation

All participants receive active buspirone for 1 month

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Buspirone

Trial Overview The trial tests whether Buspirone, a medication typically used for anxiety, can help control post-TBI irritability and aggression compared to a placebo. Patients will be randomly assigned to receive either Buspirone or an inactive pill.

How Is the Trial Designed?

Group I: Buspirone Treatment Experimental Treatment 1 Intervention

starting at 15 mg/day and ending at 60 mg/day as prescribed

Group II: Buspirone Placebo Placebo Group 1 Intervention

placebo tablets as prescribed

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

Approved in United States as Buspar for:

• Generalized anxiety disorder

Approved in European Union as Buspirone for:

• Generalized anxiety disorder

Approved in Canada as Buspirone for:

• Generalized anxiety disorder

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Published Research Related to This Trial

Buspirone operates primarily through the 5-HT1A serotonin receptor, which leads to minimal sedation and cognitive impairment, making it a unique anxiolytic compared to traditional medications like benzodiazepines.

Unlike benzodiazepines, buspirone has a slower onset of action and a lower risk of dependence, although it may not completely replace benzodiazepines in all clinical situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buspirone--frontrunner of a new genre of anxiolytics. Straughan, JL., Conradie, EA.[2014]

Buspirone is an anxiolytic medication that works differently from traditional benzodiazepines, showing comparable effectiveness to diazepam in reducing anxiety but with significantly less sedation and no abuse potential.

It acts as both a dopamine agonist and antagonist, interacting with various neurochemical systems in the brain, and has a rapid onset of action, achieving peak serum concentrations within one hour.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buspirone hydrochloride: a unique new anxiolytic agent. Pharmacokinetics, clinical pharmacology, abuse potential and clinical efficacy. Goldberg, HL.[2019]

In a study involving 96 male rats with traumatic brain injury (TBI), the serotonin(1A) receptor agonist buspirone (BUS) at a dose of 0.3 mg/kg significantly improved cognitive performance and provided histological protection by reducing cortical lesion size, compared to a saline control.

The results suggest that buspirone has a narrow therapeutic window, with the 0.3 mg/kg dose being optimal for enhancing spatial learning and memory after TBI, indicating its potential as a new treatment option for clinical TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traumatic brain injury-induced cognitive and histological deficits are attenuated by delayed and chronic treatment with the 5-HT1A-receptor agonist buspirone. Olsen, AS., Sozda, CN., Cheng, JP., et al.[2021]

Buspirone, an anxiolytic with a low side effect profile, was tested on 14 developmentally disabled individuals exhibiting anxiety and aggressive behaviors, with 9 showing favorable responses to the treatment.

The study highlights the potential of buspirone as a therapeutic option for managing anxiety and related behaviors in this population, supported by detailed case reports of 3 responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons. Ratey, JJ., Sovner, R., Mikkelsen, E., et al.[2013]

In a study of 25 prepubertal psychiatric inpatients, buspirone was associated with a significant reduction in depressive symptoms (52%) and aggressivity (29%) among the 19 children who completed the treatment, indicating some efficacy in managing anxiety and aggression.

However, 25% of participants experienced increased aggression or agitation, highlighting potential behavioral risks associated with buspirone in this population, suggesting that while it may help some children, it can also exacerbate symptoms in others.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buspirone treatment of psychiatrically hospitalized prepubertal children with symptoms of anxiety and moderately severe aggression. Pfeffer, CR., Jiang, H., Domeshek, LJ.[2013]

Buspirone is effective for treating generalized anxiety and depression, either alone or in combination with antidepressants, making it a versatile option for these conditions.

It may also help manage irritability and aggression in older adults with dementia and has potential benefits when combined with melatonin for promoting neurogenesis, although more studies are needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buspirone: Back to the Future. Howland, RH.[2015]

Buspirone, particularly at a dose of 0.1 mg/kg, significantly improved cognitive performance and reduced brain lesion size in postnatal day-17 male rats after traumatic brain injury, indicating its potential efficacy in treating pediatric TBI.

Combining buspirone with environmental enrichment led to even greater improvements in spatial learning and memory, suggesting an additive effect that could enhance rehabilitation strategies for children recovering from brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combined therapeutic regimen of buspirone and environmental enrichment is more efficacious than either alone in enhancing spatial learning in brain-injured pediatric rats. Monaco, CM., Gebhardt, KM., Chlebowski, SM., et al.[2021]

In a study of 20 hospitalized patients with organic-related psychiatric diagnoses, buspirone therapy was associated with significant improvements in aggressive behaviors, with 90% of subjects showing behavioral improvement over at least 3 months.

Buspirone was well tolerated and led to at least a 50% reduction in aggressive symptoms in 60% of the patients, suggesting its potential effectiveness for managing aggression in individuals with conditions like traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buspirone's efficacy in organic-induced aggression. Stanislav, SW., Fabre, T., Crismon, ML., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01821690

Buspirone for the Treatment of Traumatic Brain Injury (TBI) ... The purpose of this study is to improve behavior control displayed by persons with traumatic brain injury by assessing effectiveness of treatments for post-TBI ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8195453/

Buspirone's Efficacy in Organic-Induced Aggression Nine (90%) of 10 subjects for whom data were available for at least 3 months showed an improvement in behavior by study endpoint, and 6 (60%) showed at least a ...

3. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/jnp.10.1.113

Buspirone and Brain Injury Buspirone is potentially effective in treating aggression associated with mental retardation 1 and dementia.

4. cochranelibrary.com cochranelibrary.com/central/doi/10.1002/central/CN-01541332/

Buspirone for the Treatment of Traumatic Brain Injury (TBI) ... Buspirone for the Treatment of Traumatic Brain Injury (TBI) Irritability and Aggression. NCT01821690. https://clinicaltrials.gov/ct2/show/NCT01821690, ...

5. withpower.com withpower.com/trial/phase-aggression-4-2013-8723c

Buspirone for Traumatic Brain Injury Irritability and ... Buspirone was well tolerated and led to at least a 50% reduction in aggressive symptoms in 60% of the patients, suggesting its potential effectiveness for ...

6. journals.sagepub.com journals.sagepub.com/doi/abs/10.1089/neu.2012.2385

Evaluation of a Combined Treatment Paradigm Consisting ... CA3 cell loss was reduced in the TBI+EE+buspirone and TBI+EE+vehicle groups. Motor recovery, spatial learning, and memory retention were enhanced in the TBI+EE+ ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01821690

Buspirone for the Treatment of Traumatic Brain Injury (TBI) ... PURPOSE OF PROJECT: To study the effect expressed by persons with TBI through assessment of buspirone effectiveness for post-traumatic irritability and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3390982/

Traumatic Brain Injury-Induced Cognitive and Histological ... The aim of this study was to evaluate the potential efficacy of the serotonin1A (5-HT1A) receptor agonist buspirone (BUS) on behavioral and histological outcome ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4238252/

A Combined Therapeutic Regimen of Buspirone and ... The data demonstrate that both buspirone and EE can provide cognitive and histological benefits after pediatric TBI.