Impact of Early Administration of Sertraline on Depressive Symptoms in the First Year after Traumatic Brain Injury

Abstract

The potential for sertraline administered in the first 3 months after moderate to severe traumatic brain injury (TBI) to decrease the incidence of depression in the first year after injury was assessed in a double-blinded randomized control trial. Subjects were enrolled an average of 21 days after injury (none >8 weeks) followed by oral administration of placebo (50 subjects) or sertraline 50 mg (49 subjects) for 3 months. Subjects were not depressed at the time of study initiation. Outcome was assessed using the Hamilton Depression Rating Scale (HDRS) and the Depression Scale of the Neurobehavioral Functioning Inventory (NFI). Based on intent-to-treat and efficacy subset analyses, those receiving placebo exhibited significantly greater depressive symptoms than those receiving sertraline during the first 3 months after injury while receiving placebo/drug (10% of placebo group achieving a score of 6 or greater on the HDRS, 0% of the sertraline group; p < 0.023.). There was no significant difference in depressive symptoms during the remainder of the year between the two groups. Sertraline is effective in diminishing depressive symptoms even among those not clinically depressed while the medication is being taken. However, the results do not support the idea that administration early in recovery diminishes the expression of depressive symptoms after the drug is stopped. There is no basis from this study to assume that sertraline administered early in recovery after TBI, when neurotransmitter functioning is often altered, has ongoing effects on the serotonin system after sertraline is discontinued.

Evaluating the Psychometric Properties of 3 Depression Measures in a Sample of Persons With Traumatic Brain Injury and Major Depressive Disorder

“…The HAM-D has been used in depression trials among those with TBI. [32][33][34][35][36] Despite its frequent use, to date only 1 study has validated the 17-item HAM-D as a screen for MDD in a TBI sample. 37 The HAM-D had a sensitivity of 93% and specificity of 78% on the basis of a cut-point of 7.…”

Towards clinical management of traumatic brain injury: a review of models and mechanisms from a biomechanical perspective

“…Potential TBI pharmacotherapies were tested in 11 post-acute RCTs, with positive treatment effects reported in six studies, including for methylphenidate (Whyte et al, 2004; Willmott and Ponsford, 2009), CDP-choline (Calatayud Maldonado et al, 1991) and pyritinol (Kitamura, 1981). A trial of phenytoin and carbamazepine was negative (Smith et al, 1994), and sertraline, carbamazepine, rivsatigmine and modafinil were found to have no significant treatment effects (Banos et al, 2010; Jha et al, 2008; Novack et al, 2009; Tenovuo et al, 2009). …”

Depression Trajectories during the First Year after Traumatic Brain Injury

“…1,3,6 Depression is associated with adverse outcomes including greater physical disability, 2 unemployment, 7 functional dependence, 8 post-concussive symptoms, 8,9 lower quality of life, 2,9 poor psychosocial functioning and community participation, 2,4,10,11 and suicidal ideation. [12][13][14] Thus far, there is mixed evidence for the efficacy of telephone counseling or antidepressants to prevent [15][16][17] or treat patients with depression after TBI. [18][19][20] A major gap in our knowledge has to do with the course of depressive symptoms after TBI.…”