Depression

In Canada, it is estimated that approximately 11% of men and 16% of women will suffer from depression in their life-time (Health Canada 2009). For those who sustain an ABI, depression is the most common mood disorder diagnosed (Jean-Bay 2000; Jorge & Starkstein 2005; Seel et al. 2010; Underhill et al. 2003). It is however, very difficult to diagnose due to the complexities of the brain injury itself (Underhill et al. 2003). Studies have suggested the development of depression may be related to the location of injury, a pre-existing condition, personality type, family support, social support post injury and/or neurochemical imbalances (Jorge & Starkstein 2005; Ownsworth & Oei 1998; Rosenthal et al. 1998). Psychological stressors, being employed pre injury but not post, and older age are also predictors of depression among the ABI population (Sigurdardottir et al. 2013). Complicating the diagnosis is the lack of consistency in the tools used to measure depression post injury (Jorge & Starkstein 2005). 

Lesion Location and Depression

Research has investigated the link between the area of brain that has been damaged and the occurrence of depression. Results indicate that those found to have left anterior (dorsolateral frontal or basal ganglia), parietal-occipital, or right hemisphere lesions were more likely to be diagnosed with depression (Fedoroff et al. 1992; Jorge et al. 2004).  

Incidence and Prevalence

Studies looking at depression following ABI have noted that depression or depressive symptoms can begin within the first 3 months of injury but may also become evident much later. Depression occurring within the first year has been noted in 18 to 39% of those injured (McKinlay et al. 1981). However, in studies looking at depression in individuals who were one or more years post injury, prevalence rates ranged from 13 to 61% (Fleminger et al. 2003; Gordon et al. 1998; Osborn et al. 2014; Sigurdardottir et al. 2013). The risk for depression is high post ABI and remains this way for decades post injury (Hoffman et al. 2010). More specifically, a meta-analysis conducted by Osborn et al. (2014) report 21-43% of individuals have depression within the first 5 years of TBI and then after 5 years rates stabilized around 22%, which is still high compared to the general population. Further, distinguishing between depression and the behaviours resulting from the injury can prove to be challenging as there is overlap between symptoms. For example, the gradual decline in one’s ability to perform everyday tasks, the ability to cope with everyday stressors, and an increase in irritability and behavioural issues (e.g., anger, frustration, agitation) may be symptoms of depression or brain injury (Fleminger et al. 2003). Additional observational studies looking at depression can be found in the table below.

Table: Non-Intervention Studies Examining Depression

Pharmacological Treatments for Depressions

Post ABI, depression is often treated pharmacologically. Included among these Interventions are various antidepressants: serotonin selective re-uptake inhibitors such as paroxetine, sertraline, or citalopram; serotonin norepinephrine reuptake inhibitors such as duloxetine; and tricyclic antidepressants such as amitriptyline. The use of tricyclic antidepressants is however, often restricted to the treatment of headaches in those who have sustained a mild TBI because their side effects (memory impairment, sedation, etc.) have proven to be problematic in individuals who have sustained more a moderate or severe brain injury (Bajo et al. 1999). Anticonvulsants such as carbamazepine have also been used to treat depression post ABI.

Table: Pharmacological Interventions used to Treat Depression Post ABI

Discussion

Some research has been conducted exploring the effects of sertraline, citalopram, carbamazepine, desipramine and methylphenidate on the treatment of depression or depressive symptoms post ABI. A single, small sample Randomized Control Trial (RCT) found that desipramine was effective in treating long-standing depression (Wroblewski et al. 1996). Three of those in the treatment group and three in the control group had near complete resolution of depression; however, additional studies are necessary before firm conclusions are drawn on this medication.

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 and a placebo and found improvements over time for both groups on all three outcomes (the Hamilton Rating Scale for Depression, 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 Hamilton Rating Scale for Depression); 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 the end of the study (Lee et al. 2005). Further, fewer adverse events were reported for individuals receiving, methylphenidate than those administered sertraline.

The remaining three studies looked at citalopram. 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 citalopram and carbamazepine were given to patients post TBI diagnosed with depression, after 12 weeks, scores on the Brief Psychiatric Rating Scale and the Clinical Global Impression were significantly improved.

Conclusions

There is conflicting evidence that sertraline is effective in the treatment of major depression post-traumatic brain injury.

There is Level 2 evidence that citalopram aids in the reduction of depression post-acquired brain injury.

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

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

 

 

The effectiveness of sertraline in treating depression post-traumatic brain injury is unclear.

Citalopram and carbamazepine may be effective in the treatment of mood disorders.

Desipramine may be effective in reducing depression.

Results of various surveys indicate that those who have sustained an acquired brain injury have a higher incidence of depression post injury.

 

Non-Pharmacological Treatments for Depression

Several non-pharmacological Interventions have been used to treat depression post ABI including: exercise, team sports, providing them with supports through an interdisciplinary team, or counselling (Knottnerus et al. 2007). Various interventions are summarized in this section. 

Table: Non-Pharmacological Treatments used to Treat Depression Post ABI

Discussion

Several studies were found that specifically evaluated non-pharmacological interventions for depression post ABI. Among these studies the efficacy of exercise and its role in reducing the levels of depression was investigated (Bellon et al. 2015; Blake & Batson 2009; Damiano et al. 2016; Driver & Ede 2009; Gemmell & Leathem 2006; Gordon et al. 1998; Hoffman et al. 2010; Mackelprang et al. 2014; Weinstein et al. 2016; Wise et al. 2012). Overall, although improvements in mood were seen with exercise (Bellon et al. 2015; Driver & Ede 2009; Gordon et al. 1998; Weinstein et al. 2016), it was not always significantly better than the controls (Damiano et al. 2016; Gemmell & Leathem 2006). A major difference noted was for individuals who exercised more than 90 minutes per week and those who exercised less. Those in the first group (>90 minutes) showed significantly lower depression scores, better mental health and a higher perceived quality of life (Hoffman et al. 2010; Wise et al. 2012). Moreover, individuals who performed home-based aerobic exercise for 30 minutes a day did not have a significant reduction in depression; however, a decrease in depressive mood was associated with better sleep quality after working out (Damiano et al. 2016). Interestingly, there was a marked reduction in mood disturbance after only one supervised aerobic exercise session found in another study (Weinstein et al. 2016). Two studies investigated the benefits of the Chinese exercise methods Tai Chi Qigong (Blake & Batson 2009) and Tai Chi Chaun (Gemmell & Leathem 2006) on those who had sustained a TBI. Results from both these studies found an improvement in mood. However, due to the small sample sizes in each study limited conclusions can be drawn on their effectiveness in reducing depression.

Other non-pharmacological interventions are teaching coping skills, compassion focused therapy and CBT. In two RCTs conducted by Anson and Ponsford (2006a, 2006b), individuals who participated in the CSG, increased their adaptive coping skills. However, no significant changes in patients’ anxiety, self-esteem, depression or psychosocial scores were noted following the CSG. In the second study, those who had a greater self-awareness following their injuries demonstrated better outcomes post CSG intervention (Anson & Ponsford 2006b). Ruff and Niemann (1990) compared subjects who participated in an eight week cognitive remediation programme with subjects attending a treatment day program. As measured by the Katz Adjustment Scale, both groups experienced a decrease in depressed mood. In regards to compassion focused therapy, Ashworth et al. (2015) found a reduction in depression and anxiety, but also that individuals learned to be more positive and compassionate with themselves.

Two RCTs compared patients who received CBT for 12-16 weeks to patients who received supportive psychotherapy (Ashman et al. 2014; D'Antonio et al. 2013). Overall depression scores decreased compared to baseline, yet no between group differences were found (Ashman et al. 2014; D'Antonio et al. 2013). A third study compared CBT delivery methods and found no significant difference between treatment in person and treatment over the phone. However, individuals who underwent CBT had a larger decrease in depressive symptoms if they did not have a history of depression prior to TBI (Fann et al. 2015). Stalder-Lüthy et al. (2013) conducted a systematic review and report that CBT is effective for the treatment of depression for individuals who have experienced a TBI.

Three studies looking at the efficacy of mindfulness-based stress reduction (MBSR) programs on depression post ABI were conducted by Bedard and colleagues (Bedard et al. 2003; Bedard et al. 2012; Bedard et al. 2014). After a small pilot study (Bedard et al. 2003) and a pre-post study (Bedard et al. 2012) with positive results in favour of mindfulness-based stress reduction interventions reducing depression, Bedard (2014) investigated this therapy through an RCT. The programme consisted of 10 weeks of therapy designed to encourage a new way of thinking about life and disability. Results found that those in the intervention group showed a significantly greater reduction in Beck Depression Inventory scores compared to the control group with this reduction maintained at three month follow-up. In a recent pilot RCT, patients with TBI were randomly assigned to two variations of positive psychology interventions (“Three Good Things” or “Signature Strengths”) (Andrewes et al. 2014). No significant differences were found from pre-test to post test on the Authentic Happiness Scale or the Head Injury Semantic Differential Scale, although participants in the “Three Good Things” intervention, scored significantly higher on the happiness measure than patients in the “Signature Strengths” intervention.

Studies investigating music as an intervention have demonstrated positive results related to patient mood. In an early repeated measures design, patients who received standard rehabilitation plus music had greater improvements in reported mood in comparison to patients who received standard rehabilitation only (Nayak et al. 2000). More recently, both listening to music and active music therapy (e.g. playing a musical instrument, singing or writing a song) improved mood (symptoms of anxiety and depression) from initial assessments to final assessments (Guétin et al. 2009). Another study had participants in a treatment group participate in 4 sessions focussing on attention, memory, executive function and emotional adjustment followed by a 30 minute neurologic music therapy program while a control group completed various assessments and sat quietly for 30 minutes after the assessments (Thaut et al. 2009). Although there were no improvements on cognitive measures, participants in the intervention group improved on depression and anxiety subscales and both groups improved on the BSI-18 (Thaut et al. 2009).

Although there is preliminary evidence for a number of non-pharmacological interventions for mood, in particular the treatment of depression, given the limited evidence, non-pharmacological interventions cannot be considered as alternatives to pharmacological interventions. However, non-pharmacological treatments may help augment the action of antidepressants and should therefore be part of the treatment of depression post ABI.

Conclusions

There is Level 1a evidence that individuals with a traumatic brain injury who participate in exercise programs report feeling less depressed and report experiencing greater quality of life post injury.

There is Level 1b evidence that mindfulness-based stress reduction programmes may be efficacious in reducing depressed mood.

There is Level 3 evidence that music therapy does improve depression and anxiety post-acquired brain injury.

There is Level 4 evidence that Systematic Motivational Counselling may reduce negative affect.

There is Level 1b evidence that both Cognitive Behavioural Therapy and supportive psychotherapy may decrease symptoms associated with depression.

There is Level 2 evidence that positive psychology, involving patients writing down things they enjoy, is beneficial in improving happiness scores.

There is Level 4 evidence that rehabilitation decreases self-reported depression scores.

 

Music therapy may be more efficacious in improving anxiety and depression than standard rehabilitation alone.

Systematic Motivational Counselling may reduce negative affect.

Teaching coping skills to those who have sustained a traumatic brain injury helps to reduce anxiety and depression.

Compassion Focused Therapy may reduce depression and anxiety while improving self-compassion.

Exercise is associated with feeling less depressed and an improved quality of life post-traumatic brain injury.

A mindfulness-based stress reduction programme may be efficacious in reducing depressed mood.

Cognitive Behavioural Therapy and supportive psychotherapy may decrease patient symptoms associated with depression.

There is no difference in reduction of depressive symptoms between Cognitive Behavioural Therapy delivered over the phone or in person.

Positive psychology, involving patients writing down things they enjoy in life, may increase patient happiness.

Individualized rehabilitation may decreases feelings of depression.