Disorders of mood, including agitation, anxiety disorders, and major depression are all common following an ABI and are associated with suffering, worsening of other ABI sequelae, and poorer outcomes. The most common mood disorder after brain injury is a major depressive episode or depression (Jorge et al. 2004). A major depressive episode can result in hopelessness, feelings of grief or guilt, agitation, hopelessness, poor appetite, loss of libido and alterations in sleep. While ABI itself may also cause symptoms of sadness, grief, hopelessness, etc., a major depressive episode may slow the process of rehabilitation and may interfere with an individual’s ability to return to work or their relationships with family and friends (Jorge et al. 2004). For a more detailed discussion of anti-depressants and the effect on depression post ABI please refer to Module 8.


Table: Effects of Sertraline on Depression


Two RCTs looked at the effects of sertraline on depression post ABI (Ashman et al. 2009; Lee et al. 2005). Ashman et al. (2009) compared sertraline to placebo and found improvements over time for both groups on all three outcomes (the Hamilton Rating Scale for Depression (HAM-D), the Beck Anxiety Inventory (BDI), and the Life-3 Quality of Life scales). No statistically significant differences were shown between the two groups; therefore the changes may not have been related to sertraline. The second RCT added a third arm to their trial. The authors randomized individuals with mild or moderate TBI to a sertraline, methylphenidate or placebo group (Lee et al. 2005). Similar to the first study, all participants improved on the depression measures (BDI and HAM-D). However, the study results indicated that those assigned to the sertraline and the methylphenidate groups reported significantly less depressive symptoms on these measures than the placebo group at study’s end (Lee et al. 2005). Further, fewer adverse events were reported for individuals receiving methylphenidate than those administered sertraline.


There is conflicting evidence that sertraline is effective in the treatment of major depression post TBI.


The effectiveness of sertraline in treating depression post TBI is unclear.



Table: Effects of Citalopram on Depression


Rapoport and colleagues (2008) administered 20 mg/day of citalopram for 6 weeks to one group while the second group began with 20 mg/day which was titrated to a maximum of 50 mg/day. The second group was studied for 10 weeks. For participants in both groups, their depression scores significantly decreased compared to baseline. In another study participants were randomly assigned to receive citalopram or placebo (Rapoport et al. 2010). Post-treatment relapse rates were calculated for each group and there were no significant differences noted between the groups with individuals relapsing (meeting criteria for major depressive disorder) 22 to 24 weeks post treatment; relapse occurred in 52.4% of patients. In both studies, adverse events were common (Rapoport et al. 2008; Rapoport et al. 2010). While citalopram on its own has shown potential to aid with depression, a study by Perino et al. (2001) found that when both citalopram and carbamazepine were given to patients diagnosed with post-TBI depression, scores on the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) significantly improved after 12 weeks.


There is Level 2 evidence that citalopram aids in the reduction of depression post ABI.

There is Level 4 evidence that citalopram and carbamazepine may be efficacious in the treatment of depression, anxiety and mood disorders.


Citalopram is helpful in the reduction of depression post ABI.

Citalopram and carbamazepine are effective in the treatment of mood disorders.



Table: Effects of Desipramine on Depression Post ABI


A single, small sample RCT found that desipramine was effective in treating long-standing depression. Three of those in the treatment group and three in the control group had near complete resolution of depression; however, because the control group was crossed over to the treatment group, further studies are necessary before firm conclusions are drawn on this medication.


There is Level 2 evidence to suggest that the administration of desipramine assists in improving mood and reducing depression.


Desipramine is effective in reducing depression.


Sertraline and Amitriptyline

Two studies examined the effect of antidepressants on reducing agitation and/or aggression in patients with brain injuries (Kant et al. 1998; Mysiw et al. 1988). Kant et al. (1998) examined the effect of sertraline, a serotonin selective reuptake inhibitors (SSRI), on reducing aggression and irritability in patients with brain injury, whereas Mysiw et al. (1988) examined the effect of amitriptyline (a tricyclic antidepressant (TCA) with both serotonergic and noradrenergic reuptake inhibition).

Table: Effects of Sertraline and Amitriptyline on Reducing Aggression and Irritability


Both studies showed potential to improve aggressive and agitated behaviour in patients with brain injuries. Kant et al. (1998) examined the effect of sertraline HCl (Zoloft) on reducing aggression and irritability in patients with closed head injuries of varying severities, two years post injury. The patients responded positively at both 4 and 8 week follow-ups, showing significant reduction in aggressive and irritable behaviour (Kant et al. 1998). The patients treated also had improvements in depression at week 4. Mysiw et al. (1988) focused on 20 individuals who displayed agitation during their rehabilitation program and received amitriptyline. A total of 70% of patients displayed significant reductions agitation within the first week (Mysiw et al. 1988). Both studies had similar limitations, those being small sample sizes and no true control groups.


There is Level 4 evidence that sertraline HCl can decrease the incidence of aggression and irritability.

There is Level 4 evidence that amitriptyline can be useful in reducing the incidence of agitated behaviour.


Sertraline HCl can be useful in reducing aggressive and irritable behaviours.

Amitriptyline can be used to decrease agitation.