NCT04400266 · Massachusetts General Hospital
Buspirone and Melatonin for Depression Following Traumatic Brain Injury
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Buspirone
Buspirone 15mg once daily
DRUG
Mealatonin
Melatonin 3mg once nightly
Primary outcome measures
Depression
Time frame: 6 weeks
Hamilton Depression Rating Scale (HDRS); Min. value: 0; Max, value: 62; Higher number indicates higher severity of symptoms.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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).
Where
- Boston, Massachusetts
- Charlestown, Massachusetts
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 6, 2026 · Source of record for eligibility and locations