Prophylaxis Pharmacotherapy to Prevent the Onset of Post-Traumatic Brain Injury Depression: A Systematic Review

Depression is a common psychiatric problem following traumatic brain injury (TBI) with reported prevalence rates of 30-77% in the first year post-TBI. Given the negative influence of post-TBI depression on cognition and interpersonal, social, physical, and occupational functioning, early initiation of pharmacotherapy to prevent post-TBI depression has been considered. This systematic review will synthesize the available evidence from published studies on the effectiveness and harms of pharmacotherapy for the secondary prevention of post-TBI depression. Studies published prior to October 2018 were eligible for inclusion. Six databases were searched, with additional searching of key additional documents. Studies meeting inclusion criteria were evaluated for methodological quality. Six articles addressing five studies met inclusion criteria. Study designs included three randomized controlled trials (RCTs), two retrospective cohorts, and one case-control. Prophylactic pharmacotherapy included antidepressants, beta-blockers and statins. In one RCT, the number needed to treat with sertraline to prevent one case of depression post-TBI at 24 weeks was 5.9 (95% confidence interval [CI]: 3.1-71.1). In a second RCT affected by significant attrition, sertraline had no effect. Prescribing beta-blockers prior to TBI reduced the depression risk regardless of the specific brain trauma. TBI patients with pre-existing hyperlipidemia not treated with statins had an increased risk for depression compared with those without hyperlipidemia. Overall, this systematic review yielded mixed evidence of prophylactic efficacy and insufficient evidence of harm. In the absence of tolerability data, existing data are insufficient to recommend sertraline prophylaxis. Optimal timing and treatment duration with identification of patients most likely to benefit from prophylaxis require further consideration. Dedicated prospective studies assessing the effects of beta-blockers and statins on post-TBI depression are required.