Buspirone for Traumatic Brain Injury Irritability and Aggression

Overseen by Flora Hammond, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Indiana University

Must not be taking: Buspirone

Disqualifiers: Schizophrenia, Psychosis, Neurologic disease, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing buspirone, a medication usually used for anxiety, to see if it can help reduce irritability and aggression in people who have had a traumatic brain injury. The study involves 74 participants who will receive buspirone. The goal is to see if buspirone can make a positive difference in their behavior by calming the brain. Buspirone is a new anxiolytic agent that has been shown to reduce aggression and anxiety without causing sedation or cognitive side effects.

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 data supports the effectiveness of the drug buspirone for treating irritability and aggression in traumatic brain injury?

Research suggests that buspirone may help reduce aggressive behaviors in individuals with brain injuries, as one study found that 90% of patients showed improved behavior after treatment. Additionally, in animal studies, buspirone improved cognitive performance after brain injury, indicating potential benefits for similar conditions. ^{1 2 3 4 5}

Is buspirone generally safe for humans?

Buspirone is generally considered safe for humans, with a low side effect profile and minimal sedation or cognitive dysfunction. It has been well tolerated in studies involving individuals with aggressive behaviors and anxiety, including those with traumatic brain injury and developmental disabilities. ^{1 2 3 4 6}

How is the drug buspirone unique for treating irritability and aggression after traumatic brain injury?

Buspirone is unique because it is a serotonin receptor agonist that can improve cognitive performance and reduce aggression without the sedating effects common in other treatments. It also has no abuse potential, making it a safer option for managing irritability and aggression in traumatic brain injury patients. ^{1 3 5 7 8}

Research Team

Flora Hammond, MD

Principal Investigator

Indiana University/Rehabilitation Hospital of Indiana

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Buspirone (Anxiolytic)

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.

Participant Groups

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 Canada for the following indications:

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+

Alan Palkowitz

Indiana University

Chief Executive Officer since 2020

PhD in Chemistry from Indiana University

David Ingram

Indiana University

Chief Medical Officer since 2020

MD from Indiana University School of Medicine

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Buspirone's efficacy in organic-induced aggression. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Buspirone treatment of psychiatrically hospitalized prepubertal children with symptoms of anxiety and moderately severe aggression. [2013]

3. United States 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. [2021]

4. South Africa pubmed.ncbi.nlm.nih.gov

Buspirone--frontrunner of a new genre of anxiolytics. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons. [2013]

7. United States 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Buspirone: Back to the Future. [2015]