Sertraline Monotherapy May Not Be Enough for Patients With Complicated TBI, MDD

More than 50 percent of patients with traumatic brain injury (TBI) may develop major depressive disorder (MDD), but it is still unclear how antidepressants can best be used for this population.

So far, studies show that the selective serotonin reuptake inhibitor (SSRI) sertraline is more effective in preventing, rather than treating, depression in people with TBI. A 2016 JAMA Psychiatry study found when sertraline was used as a preventive agent soon after a TBI, only 6 percent of participants taking the medication (100 mg/day) developed MDD after 24 weeks, compared with 22 percent in the placebo group.

A study published in the September/October 2017 issue in the Journal of Head Trauma Rehabilitation evaluated sertraline when used as a treatment, and found it was no more effective than placebo for MDD in participants during the first year following a complicated mild to severe TBI. The mean number of months since injury was 4.3 for the sertraline group and 4.9 for the placebo group.

Principal investigator Jesse Fann, M.D., M.P.H., a professor of psychiatry and behavioral sciences at the University of Washington School of Medicine, and colleagues conducted the double-blind, placebo-controlled trial to determine the effect of sertraline on depression symptoms after 12 weeks.

Although depression improved from baseline to 12 weeks in both treatment groups (as indicated by 17-item Hamilton Depression Rating Scale), “there were no significant differences between the sertraline and placebo groups after 12 weeks on depression severity, response, or remission,” wrote Fann and colleagues.

Fann told Psychiatric News that a higher discontinuation rate in the sertraline group, high psychiatric comorbidity in the sample, and high response to placebo due to frequent in-person follow-ups may explain why there were no differences between the groups. Of the 62 participants randomized to sertraline or placebo, 32 percent had sustained severe TBI, 68 percent had significant anxiety, 63 percent had a history of prior MDD, and 69 percent had a history of alcohol or drug dependence.

Fann also noted that in the treatment study, over half of the participants had moderate-to-severe TBI, while in the prevention study, nearly 80 percent had mild TBI (sertraline may be more effective in cases where TBI is not as severe).

“One cannot conclude from this study that sertraline may not be potentially helpful for a given person with TBI and depression. What we can conclude is that many patients with complicated mild-to-severe TBI may need more than a single trial of an antidepressant and may benefit from further treatment adjustments, such as augmentation with or switch to a different medication or psychotherapy,” Fann said. “Many people with TBI have depression that is associated with significant psychosocial stressors; therefore, antidepressants alone may not adequately treat these cases.” The sertraline group showed significant improvement on speed of information processing compared with the placebo group, according to the study.

No large studies have been conducted comparing different antidepressants in this patient population, said Fann. “There have been other trials that have suggested efficacy with other medications, but most of them have significant methodological shortcomings, such as small sample size and inadequate controls,” he said. “Clearly, more research is needed in this area, including the study of multifaceted and stepped care approaches to treatment.”

The research was supported by the National Center for Medical Rehabilitation Research, the National Institute of Child Health and Human Development, and the National Institutes of Health. ■