The Effect of Antidepressants on Depression After Traumatic Brain Injury: A Meta-analysis

Abstract

Objective: Following traumatic brain injury (TBI), depressive symptoms are common and may influence recovery. We performed a meta-analysis to estimate the benefit of antidepressants following TBI and compare the estimated effects between antidepressants and placebo.

Participants: Multiple databases were searched to find prospective pharmacological treatment studies of major depressive disorder (MDD) in adults following TBI.

Main measures: Effect sizes for antidepressant medications in patients with TBI were calculated for within-subjects designs that examined change from baseline after receiving medical treatment and treatment/placebo designs that examined the differences between the antidepressants and placebo groups.

Design: A random-effects model was used for both analyses.

Results: Of 1028 titles screened, 11 were included. Pooled estimates showed nonsignificant difference in reduction of depression scores between medications and placebo (standardized mean difference of 5 trials = -0.3; 95% CI, -0.6 to 0.0; I = 17%), and a significant reduction in depression scores for individuals after pharmacotherapy (mean change = -11.2; 95% CI, -14.7 to -7.6 on the Hamilton Depression Scale; I = 87%).

Conclusions: This meta-analysis found no significant benefit of antidepressant over placebo in the treatment of MDD following TBI. Pooled estimates showed a high degree of bias and heterogeneity. Prospective studies on the impact of antidepressants in well-defined cohorts of TBI patients are warranted.

Figure 1.

Exclusions for prior antidepressant use were defined as excluding for any prior use of antidepressants. Note that the following studies were defined as not excluding for prior antidepressant use for the following reasons: Lee et al, Newburn et al, and Rapoport et al excluded patients who had taken antidepressants recently or were currently taking antidepressants. Rao excluded patients with good response to other antidepressants in the past as well as patients with poor response to escitalopram in the past and patients currently taking antidepressants. Saran had a washout period of 1 week prior to study onset.

Figure 2.

Standardized mean difference in reduction of self-reported depression after treatment with antidepressant versus treatment with placebo. The combined estimate was not significant, and 80% of the studies individually did not find significant improvement in depression scores in patients who received a pharmacological treatment over patients who received a placebo.

Figure 3.

Mean change in HAM-D scores, baseline to posttreatment. Depression score was significantly reduced after pharmacological treatment post-TBI for the 8 studies reporting HAM-D score as their outcome measure, however, with high heterogeneity. HAM-D indicates Hamilton Depression Scale.