Antidepressants for Depression Associated with Traumatic Brain Injury: A Meta-analytical Study of Randomised Controlled Trials.

Introduction: Depression following traumatic brain injury is experienced by 16% to 60% of affected patients. The present study aimed to update the best evidence-based pharmacological treatments for tackling such chronic and debilitating disorders.

Methods: We systematically reviewed and meta-analysed randomised controlled trials published from 1990 until August 2017 that compared the efficacy of antidepressants with placebo in the treatment of post-traumatic brain injury depression. We searched MEDLINE, SCOPUS, and the Cochrane Central Register of Controlled Trials (CENTRAL).

Results: Four studies were eligible for the meta-analysis. The antidepressants studied were the selective serotonin reuptake inhibitors sertraline and citalopram. The rate of non-responders at the end of the follow-up period was lower in the treatment groups compared with placebo (odds ratio = 0.42, 95% confidence interval: 0.15-1.17); this difference was not statistically significant (p = 0.10). In subgroup analysis of the studies that reported mean Hamilton Depression Rating Scale score differences between treatment and control groups in both baseline and endpoint evaluations, the pooled mean difference was reduced from 2.11 (95% confidence interval: -1.25 to 5.46) to -2.36 (95% confidence interval: -5.59 to 0.87), in favour of the treatment group, though not statistically significant (p = 0.06). No evidence of heterogeneity was detected. In the subgroup analysis according to the antidepressant used in the included studies, there was a trend towards statistical significance for sertraline only (odds ratio = 0.28, 95% confidence interval: 0.08-1.03; p = 0.05); this was not evident in the study that reported the use of citalopram (odds ratio = 0.83; 95% confidence interval: 0.15-4.64; p = 0.84).

Conclusions: Sertraline might be effective, though not statistically significant, in treating patients with post-traumatic brain injury depression. Adequately powered randomised controlled trials - extended to the plethora of newer antidepressants aiming to prove their non-inferiority to the selective serotonin reuptake inhibitors studied - are needed to confirm our results. The dearth of quality studies of this devastating problem of public health is rather impressive.