Buspirone and Melatonin for Depression Following Traumatic Brain Injury

Buspirone and Melatonin for Depression Following Traumatic Brain Injury (NCT04400266) is a Phase 4 interventional studying Depression and Brain Injuries, Traumatic, sponsored by Massachusetts General Hospital. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 10 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: Patients with mild or moderate TBI will be included. To be included, a subject must meet the criteria below: 1. Non-penetrating mild or moderate traumatic brain injury that occurred 3 or more months prior to study entry (to minimize natural recovery from TBI) 2. Age: 18-64 years 3. Meeting any one of the following severity criteria, as documented in the patient's medical records: 1. Glasgow Coma Scale (GCS) score of 9-15 within 4 hours after injury 2. Loss of consciousness (LOC) \>1 minute and \<=24 hours 3. Post-traumatic amnesia (PTA) \< 7 days 4. English-speaking 5. Current DSM-5 diagnosis of Major Depressive Episode by medical record diagnosis 6. HAM-D-21 score of 18 or higher 7. Patients who are considered to be appropriate by their clinician and who are willing to be started on Buspirone and Melatonin for clinical purposes. Who Should NOT Join This Trial: 1. 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. 2. Evidence from the history of TBI severity greater than moderate, i.e., GCS of 8 or less, LOC \> 24 hours, or PTA \> 7 days. 3. Inability to attend regular appointments 4. 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. 5. Lifetime history of schizophrenia or other primary psychotic disorders, as determined by history by the patient or review of their medical records. 6. History of bipolar disorder, as determined by history by the patient or review of their medical records. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: Patients with mild or moderate TBI will be included. To be included, a subject must meet the criteria below: 1. Non-penetrating mild or moderate traumatic brain injury that occurred 3 or more months prior to study entry (to minimize natural recovery from TBI) 2. Age: 18-64 years 3. Meeting any one of the following severity criteria, as documented in the patient's medical records: 1. Glasgow Coma Scale (GCS) score of 9-15 within 4 hours after injury 2. Loss of consciousness (LOC) \>1 minute and \<=24 hours 3. Post-traumatic amnesia (PTA) \< 7 days 4. English-speaking 5. Current DSM-5 diagnosis of Major Depressive Episode by medical record diagnosis 6. HAM-D-21 score of 18 or higher 7. 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: 1. 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. 2. Evidence from the history of TBI severity greater than moderate, i.e., GCS of 8 or less, LOC \> 24 hours, or PTA \> 7 days. 3. Inability to attend regular appointments 4. 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. 5. Lifetime history of schizophrenia or other primary psychotic disorders, as determined by history by the patient or review of their medical records. 6. History of bipolar disorder, as determined by history by the patient or review of their medical records. 7. Alcohol or substance dependence in the past 3 months, as determined by history by the patient or review of their medical records. 8. Pregnancy or breast-feeding 9. Concomitant use of buspirone, any psychostimulant, or modafinil/armodafinil 10. Patients currently on an antidepressant or who have been on antidepressant in the past 4 weeks 11. Patients with prior intolerances to buspirone or melatonin. 12. Conditions that would preclude a subject from participating in the MRI procedures (e.g., metal implants, aneurysm clips, shrapnel/retained particles, pacemakers, claustrophobia).

Treatments Being Tested

DRUG

Buspirone

Buspirone 15mg once daily

DRUG

Mealatonin

Melatonin 3mg once nightly

Locations (2)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Massachusetts General Hospital

Boston, Massachusetts, United States

Massachusetts General Hospital Home Base Program

Charlestown, Massachusetts, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04400266), the sponsor (Massachusetts General Hospital), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04400266 clinical trial studying?

Who can participate in NCT04400266?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04400266?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04400266. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04400266. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.