Pharmacological and Non-Pharmacological Interventions for Depression after Moderate-to-Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

The objective of this study was to systematically review the literature and perform a meta-analysis of randomized controlled trials (RCTs) on the effectiveness of pharmacological and non-pharmacological interventions for depression in patients with moderate-to-severe traumatic brain injury. Databases searched were: Embase, PubMed, PsycInfo, Cochrane Central, Web of Science, and Google Scholar. Depression score on a self-report questionnaire was the outcome measure. Outcomes were collected at baseline and at the first follow-up moment. Data extraction was executed independently by two researchers. Thirteen RCTs were identified: five pharmacological and eight non-pharmacological. Although not all individual studies had significant results, the overall standardized mean difference (SMD) was -0.395, p ≤ 0.001, indicating that interventions improved the depression scores in patients with TBI. The difference in effectiveness between pharmacological interventions and non-pharmacological interventions was not significant (ΔSMD: 0.203, p = 0.238). Further subdivision into methylphenidate, sertraline, psychological, and other interventions showed a significant difference in effectiveness between methylphenidate (ΔSMD: -0.700, p = 0.020) and psychological interventions (reference). This difference was not found if other depression outcomes in four of the included studies were analyzed. The SMD of low-quality studies did not differ significantly from moderate- and high-quality studies (ΔSMD: 0.321, p = 0.050). Although RCTs targeting interventions for depression after TBI are scarce, both pharmacological and non-pharmacological interventions appear to be effective in treating depressive symptoms/depression after moderate-to-severe TBI. There is a need for high-quality RCTs in which the add-on effects of pharmacological and non-pharmacological interventions are investigated.