Pharmacotherapy May Reduce Depressive Symptoms After Traumatic Brain Injury

In comparison with the effectiveness of treatment for major depressive disorder, researchers were inconclusive in determining that pharmacotherapy is effective for treating depression after a traumatic brain injury.

Pharmacologic treatment may be effective to relieve depressive symptoms in patients with traumatic brain injury, but further studies with larger samples are needed to support efficacy outcomes, according to a study published in The Journal of Neuropsychiatry and Clinical Neurosciences.

The investigators of this study sought to systematically review available evidence for the effectiveness of pharmacotherapy to treat depression following a traumatic brain injury. The study investigators searched relevant online databases (PubMed, Cochrane Database, Google Scholar, and the National Institute of Health and Care Excellence Healthcare Databases Advanced Search) for studies measuring the effect of pharmacologic treatments for depression in patients with traumatic brain injury. In the current meta-analysis, the investigators evaluated 12 studies for sample size, treatment duration, treatment used, severity of brain injury, method of assessment (randomized controlled trials or single intervention groups), and medication response; effect sizes were calculated for each study using pre- and postintervention scores. All effect sizes were then weighted and pooled to find the average effect size for both 2-group and single-group studies.

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Of the 12 included studies, 7 compared pharmacologic effects in patients with traumatic brain injury with placebo or control groups, while 5 studies contained no control group. The investigators calculated 14 different effect sizes (2 studies had multiple outcome measures) and found the summary effect size to be mild to moderate (Cohen’s d=-0.49; 95% CI, -0.96 to -0.02; P =.02). Of the 14 effect sizes, 10 were statistically significant with effect sizes larger than the pooled estimate, and 4 were considered insignificant as they had very small sample sizes, were nonrandomized, and had no control group. The weighted pooled effect size was significantly greater for single-group design studies (Cohen’s d=-1.35; 95% CI, -2.14 to -0.56) vs studies that included a comparison group (Cohen’s d=.001; 95% CI, -0.59 to 0.58).

A limitation to the meta-analysis was including single-group designs, which produced a larger pooled effect size and had a higher risk of selection bias. The inability to control for the type and severity of brain trauma, or the time since injury, also limited the meta-analysis by contributing to high heterogeneity among study outcomes.   

Findings from the current meta-analysis suggest that pharmacologic treatment for reducing depressive symptoms in patients with traumatic brain injury may be mildly to moderately effective. However, there is a lack of evidence from individual randomized controlled trials to support the beneficial effects of pharmacologic interventions for this population; future studies should focus on higher-quality designs with lower heterogeneity.


Slowinski A, Coetzer R, Byrne C. Pharmacotherapy effectiveness in treating depression after traumatic brain injury: a meta-analysis [published online January 14, 2019]. J Neuropsychiatry Clin Neurosci. doi: 10.1176/appi.neuropsych.18070158