Can Sertraline Help Prevent Depression Following a TBI?

Approximately 30 to 50 percent of patients with a traumatic brain injury (TBI) develop a depressive disorder during the first year post-injury—a factor that compromises patients’ ability to make full recovery and increases risk of long-term refractory depression.

Ricardo Jorge, M.D.

A study appearing this month in JAMA Psychiatry now suggests that giving patients a low dose of the selective serotonin reuptake inhibitor (SSRI) sertraline early after TBI may help to prevent depression.

“This is the first trial, to our knowledge, indicating that antidepressants are efficacious to prevent the onset of depression following TBI,” Ricardo Jorge, M.D., a professor of psychiatry and behavioral sciences at Baylor College of Medicine, and colleagues wrote. “Given the prevalence and functional effect of depression among patients with TBI, these findings have profound therapeutic implications.”

For the study, 94 adults who had experienced and recovered from a mild or moderate TBI and showed no symptoms of depression were randomly assigned to receive sertraline (dose increased from 25 mg/day to 100 mg/day over the study) or placebo for 24 weeks. (Sertraline is commonly prescribed at 150 to 200 mg/day for depression management.) Study participants were regularly evaluated for changes in depressive symptoms as well as cognitive function throughout the trial.

After 24 weeks, only 6 percent of patients receiving sertraline developed depression, compared with 22 percent in the placebo group. This rate calculated out to a number needed to treat of 5.9 for sertraline—that is, for every six TBI patients given sertraline prophylactically, the findings suggest one case of depression was prevented. The intervention was generally well tolerated, with mild adverse events reported in the sertraline and placebo groups.

“The fact that small doses of sertraline are efficacious to prevent depression after TBI stands in sharp contrast to the lack of efficacy of antidepressants to treat depression in the chronic stage of TBI,” the authors wrote. “Overall, these results suggest that sertraline is efficacious to prevent the onset of depressive disorders when administered early after TBI but that it has a questionable antidepressant action when depressive disorders are already present and follow a chronic course.”

Jorge and his team also explored whether sertraline might confer some cognitive benefits that would accelerate the improvement of the TBI patients. A clinical study published in 2010 by Jorge and his colleagues found that escitalopram, another SSRI, could improve cognitive functioning in recovering stroke patients.

In the current study, the sertraline group did not display any improvements in attention, working memory, or other neuropsychological measures when compared with the placebo group.

Before any clinical recommendations can be made regarding the use of sertraline for the prevention of depression following TBI, Jorge told Psychiatric News that larger and longer trials are needed. Understanding whether combining antidepressants with behavioral interventions optimizes outcomes for these patients over the long term will also be important, he said.

“These are not the first data to suggest that antidepressants can have a preventive effect on depression, but it is a little-studied area of psychiatry, and we don’t know what changes go on in the brain that offer protection for an at-risk individual,” Jorge said.

Jorge’s study was funded by a grant from the National Institute of Neurological Disorders and Stroke. ■