Depression is the most common psychiatric sequela after traumatic brain injury (TBI) and poses a variety of treatment challenges. There is a lack of clinical trials focused on biological interventions used to manage TBI depression.
The aim of this systematic review is to summarize the current evidence of psychotropic and neuromodulatory interventions used to treat TBI depression and to provide directions for future research.
Key words were used to describe the following search terms: “traumatic brain injury”, “depression”, “pharmacological/drug therapy”, and “neuromodulation”. Studies focused on pharmacotherapy or neuromodulation in TBI depression were identified in 5 databases: Medline (PubMed), EMBASE (, the Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), PsycINFO (EbscoHost), and Web of Science. Article inclusion/exclusion using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based systematic protocol of extraction and evaluation was applied. Level of evidence for each study was determined using the American Academy of Neurology criteria.
The initial search provided 1473 citations. Twenty-two studies met inclusion criteria. Sixteen studies explored pharmacological interventions with emphasis on serotonergic agents. Results between studies were conflicting, and interventions did not always outperform placebos, although sertraline provided the highest level of evidence for treatment of TBI depression. Six studies examining neuromodulatory interventions show preliminary evidence of efficacy with a range of interventions and modes of delivery used.
Additional research including large-sample randomized-controlled trials using pharmacological, neuromodulation, or combination treatment is needed. These studies should incorporate premorbid psychosocial functioning, preinjury psychiatric disease, cognitive deficits, and functional recovery when examining outcomes.

Copyright © 2020 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.