Buspirone and Melatonin for Depression Following Traumatic Brain Injury

Recruiting now · Phase 4

Conditions studied: Depression, Brain Injuries, Traumatic

In brief

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.

Key facts

Study ID: NCT04400266
Run by: Massachusetts General Hospital
People needed: 10
Starts: 2020-08-01
Expected to finish: 2028-07-31
Last updated by the study team: 2026-05-06

Who can join

Age: 18 and older, up to 64. Sex: any. Healthy volunteers: not accepted.

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).

Where it is running

Massachusetts General Hospital — Boston, Massachusetts, United States (enrolling)
Massachusetts General Hospital Home Base Program — Charlestown, Massachusetts, United States (enrolling)

Full record on ClinicalTrials.gov

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