Buspirone and Melatonin for Depression Following Traumatic Brain Injury

NCT04400266 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 2019P003783
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Traumatic brain injuries (TBIs) are common. Post-TBI depression is associated with anxiety, aggression, fatigue, distractibility, anger, irritability, and rumination. The current research group conducted a pilot clinical trial, which investigated the novel treatment combination of buspirone and melatonin (B+MEL) in outpatients with clinical depression. Compared to placebo, B+MEL was associated with a significant improvement in depressive symptoms. Depression following TBI may be different from clinical depression. The B+MEL combination has never been studied in patients with post-TBI depression. The B+MEL has shown promise in ameliorating cognitive difficulties in people with depression. Because cognitive problems are typical in people with post-TBI depression, we plan to measure the effect of the B+MEL combination on cognitive ability in post-TBI depression. Additionally, we are interested in measuring functional magnetic resonance imaging changes before and after treatment with B+MEL in order to gain insight into the brain mechanisms of our hypothesized clinical symptom changes. The goals of the proposed pilot research project are to assess changes in symptoms in patients with post-TBI depression following Buspirone + Melatonin combination (B+MEL), and the corresponding brain mechanisms underlying these hypothesized changes by measuring: 1) depressive symptoms; 2) cognitive symptoms; 3) functional magnetic resonance imaging.

Conditions

Depression; Brain Injuries, Traumatic

Outcome Measures

Primary Outcomes (1)

• Depression

  Hamilton Depression Rating Scale (HDRS); Min. value: 0; Max, value: 62; Higher number indicates higher severity of symptoms.

  6 weeks

Secondary Outcomes (1)

• Cognition

  6 weeks

Other Outcomes (1)

• Functional neuroimaging

  6 weeks

Study Arms (1)

Buspirone and Melatonin

EXPERIMENTAL

Buspirone 15mg and Melatonin 3mg

Drug: Buspirone; Drug: Mealatonin

Interventions

Buspirone DRUG

Buspirone 15mg once daily

Buspirone and Melatonin

Mealatonin DRUG

Melatonin 3mg once nightly

Buspirone and Melatonin

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with mild or moderate TBI will be included. To be included, a subject must meet the criteria below:
• Non-penetrating mild or moderate traumatic brain injury that occurred 3 or more months prior to study entry (to minimize natural recovery from TBI)
• Age: 18-64 years
• Meeting any one of the following severity criteria, as documented in the patient's medical records:
• Glasgow Coma Scale (GCS) score of 9-15 within 4 hours after injury
• Loss of consciousness (LOC) \>1 minute and \<=24 hours
• Post-traumatic amnesia (PTA) \< 7 days
• English-speaking
• Current DSM-5 diagnosis of Major Depressive Episode by medical record diagnosis
• HAM-D-21 score of 18 or higher
• Patients who are considered to be appropriate by their clinician and who are willing to be started on Buspirone and Melatonin for clinical purposes.

You may not qualify if:

• History of neurological disorder (e.g., stroke, epilepsy, multiple sclerosis, HIV, neurodegenerative disorders) or any acute or unstable medical condition that is likely to interfere with the assessments or with participation in treatment, as determined by history by the patient or review of their medical records.
• Evidence from the history of TBI severity greater than moderate, i.e., GCS of 8 or less, LOC \> 24 hours, or PTA \> 7 days.
• Inability to attend regular appointments
• Imminent risk of suicide, as determined by the assessing clinician; HAM-D, Question 3, answers \> 1; SDQ, Question 11, answers \> 3; spontaneous expressions of suicidal ideation will result in emergency evaluation by a licensed clinician member of study staff for appropriate assessment and triage.
• Lifetime history of schizophrenia or other primary psychotic disorders, as determined by history by the patient or review of their medical records.
• History of bipolar disorder, as determined by history by the patient or review of their medical records.
• Alcohol or substance dependence in the past 3 months, as determined by history by the patient or review of their medical records.
• Pregnancy or breast-feeding
• Concomitant use of buspirone, any psychostimulant, or modafinil/armodafinil
• Patients currently on an antidepressant or who have been on antidepressant in the past 4 weeks
• Patients with prior intolerances to buspirone or melatonin.
• Conditions that would preclude a subject from participating in the MRI procedures (e.g., metal implants, aneurysm clips, shrapnel/retained particles, pacemakers, claustrophobia).

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02144, United States

RECRUITING

Massachusetts General Hospital Home Base Program

Charlestown, Massachusetts, 02129, United States

RECRUITING

MeSH Terms

Conditions

Depression; Brain Injuries, Traumatic

Interventions

Buspirone

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds

Central Study Contacts

Kaloyan Tanev

CONTACT

6177267511; ktanev@partners.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a single-arm, open-label study of the Buspirone and Melatonin combination administered over 6 weeks.

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 22, 2020
• Study Start: August 1, 2020
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)