Treatment of Depression after Traumatic Brain Injury: A Systematic Review focused on Pharmacological and Neuromodulatory Interventions

Abstract Background Depression is the most common psychiatric sequela following 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. This systematic review summarizes the current evidence of psychotropic and neuromodulatory interventions used to treat TBI depression and provides directions for future research. Methods 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 five databases: Medline (PubMed), EMBASE ( Embase.com ), the Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), PsycINFO (EbscoHost), and Web of Science. Article inclusion/exclusion using PRISMA-based systematic protocol of extraction and evaluation was applied. Level of evidence for each study was determined using American Academy of Neurology criteria. Results 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, though 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. Conclusion Additional research including large-sample randomized-controlled trials using pharmacological, neuromodulation, or combination treatment are needed. These studies should incorporate premorbid psychosocial functioning, pre-injury psychiatric disease, cognitive deficits, and functional recovery when examining outcomes.