| Summary: | Abstract Background Depression is a common complication of traumatic brain injury (TBI). New evidence suggests that antidepressant medication may be no more effective than placebo in this population. Main body Selective serotonin reuptake inhibitors are recommended as first-line treatment for depression in contemporary expert consensus clinical practice guidelines for management of TBI. This recommendation is based on multiple prior meta-analyses of clinical trials in depression after TBI as well as depression in the general population. The evidence is mixed. A recent clinical trial and new meta-analysis including that trial found no benefit of antidepressants for depression following TBI. We argue that this finding should not change practice, i.e., patients who present with depression after TBI should still be considered for antidepressant treatment, because they may (1) benefit from robust placebo effects, (2) benefit from an alternative or adjunctive medication if the agent prescribed first does not achieve a depression remission, and (3) make improvements that are not captured well by traditional depression outcome measures, which are confounded by TBI sequelae. Patients with mild TBI are especially appropriate for antidepressant therapy because they, on average, more closely resemble patients with no known TBI history enrolled in typical primary Major Depressive Disorder clinical trials than patients enrolled in TBI trials in placebo-controlled trials published to date. Conclusion TBI, and especially mild TBI, is not a contraindication for antidepressant therapy. Health providers should routinely screen and initiate treatment for depression after TBI.
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