Selective serotonin reuptake inhibitors in the treatment of major depressive disorder after brain trauma: Systematic review and meta-analysis

Abstract

Background: Traumatic brain injury (TBI) poses a considerable risk to human health. After TBI, individuals are susceptible to a range of psychiatric disorders, with depression being a primary complication. Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of depression; however, their efficacy in addressing major depressive disorder (MDD) in adults following TBI remains uncertain.

Aim: To investigate the efficacy of SSRIs in the treatment of MDD after TBI.

Methods: A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, encompassing studies published until May 2024. This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI. Studies were assessed based sample size, treatment duration, treatment methodologies, severity of brain injury, assessment techniques, and drug response. A random-effects model was used to derive the summary effect size.

Results: Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment. The eight studies did not exhibit heterogeneity (I ² = 38%). The depression score for MDD after TBI in the SSRI group decreased more than that in the control group [odds ratio (OR) 1.68, 95%CI: 1.09-2.58, P = 0.02]. The adverse reactions after treatment included diarrhea, dizziness, dry mouth, nausea, or vomiting. There was no difference in the incidence of adverse reactions after treatment between the two groups (OR 1.16, 95%CI: 0.78-1.73, P = 0.46]. These studies did not show significant heterogeneity (I ² = 44%).

Conclusion: SSRIs may be effective in treating patients with MDD after TBI. Adequately powered, randomized, controlled trials are required to confirm these findings.

Keywords: Antidepressant; Depression; Meta-analysis; Selective serotonin reuptake inhibitors; Traumatic brain injury.

Figure 1

Studies included and excluded from the meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RCT: Randomized clinical trial.

Figure 2

Risk of bias in included studies. A: Risk of bias summary: Each bias risk item of all included studies was judged by review authors; B: Risk of bias graph: The review authors quantified each bias risk item of included studies as a percentage. The risk of bias assessment for each included study in accordance with “Cochrane RoB 2”. Low risk (+), unclear (?), and high risk (-).

Figure 3

Forest plot of major depressive disorder after selective serotonin reuptake inhibitor treatment of traumatic brain injury. A: Forest plot of the reduction in depression scores of major depressive disorder (MDD) after selective serotonin reuptake inhibitor (SSRI) treatment of traumatic brain injury (TBI); B: Forest plot of the incidence of adverse reactions in SSRI-treated MDD after TBI. Diamond: Pooled estimate; squares: Individual study effects; horizontal lines: Confidence intervals; MDD: Major depressive disorder; SSRI: Selective serotonin reuptake inhibitor.

Figure 4

The funnel plot of this study. A: The reduction in depression scores of major depressive disorder; B: Adverse reactions. OR: Odds ratio.