Pharmacological and non-pharmacological interventions of depression after traumatic brain injury: A systematic review
Introduction
Traumatic brain injury (TBI) is a form of brain damage whose onset usually results from insults received during military engagements, contact or extreme sports, and traffic accidents that can result in transient or permanent disorders, including movement dysfunction, mood changes and some other symptoms such as cognitive impairment (Arulsamy et al., 2018; Gill et al., 2014; Menon et al., 2010). Improvements in medical technology mean that increasing numbers of victims of TBI, even those with severe cases, can be saved. However, this entails more and more people living with various comorbidities and low quality of life. Many patients with TBI, including veterans, boxers and motorcycle riders, are young and may usually earn the main source of income for their families. Treating and taking care of such patients has thus become a considerable burden for both their families and society. As many studies have noted, mood disorders are common subsequent complications of TBI, among which depression is the most common psychiatric complication (Alway et al., 2016; Ashman et al., 2004; Fann et al., 1995). Methodological heterogeneity has yielded widely varying incidence rates of post-TBI depression from 6% to 77% (Jorge and Arciniegas, 2014). But it is clear that victims of TBI are more likely to develop depression than those without TBI (Lavoie et al., 2017).
The onset of depression following TBI is increasingly recognized as a distinct (Jorge and Starkstein, 2005) and highly prevalent (Bombardier et al., 2010) complication of TBI that is associated with greater disability and mortality after the injury event (Fann et al., 1995; Satz et al., 1998; Williamson et al., 2013). Such depression aggravates the other TBI-induced symptoms and care burden, diminishes work capability and quality of life, increases the risk of suicide (Alway et al., 2016; Fisher et al., 2016), and deteriorates the recovery outcomes of patients with TBI (Mooney et al., 2005). The consequences will, in turn, exacerbate the depression (Han et al., 2018), which forms a vicious cycle for the patients.
While much research has focused on spontaneous depression, post-TBI depression has received relatively insufficient attention clinically and remains under-treated (Bombardier et al., 2010). The lack of reliable interventions and clinical guidelines informing the treatment of depression developed after TBI may partly account for the underwhelming clinical response to the condition (Albrecht et al., 2015; Barker-Collo et al., 2013; Fann et al., 2009), warranting the exploration of solid evidence-based treatments for post-TBI depression. Moreover, the frequent resistance of patients with post-TBI depression to typical antidepressant pharmacotherapies should, along with reported efficacy in treating the condition, be gathered and discussed to inform clinical approaches to this form of depression (Saran, 1988).
While previous reports have considered pharmacological, psychological, and electrophysiological interventions for the treatment of depression following TBI, most of the studies were subject to various limitations, including small sample sizes, short follow-ups, non-strict trial designs, and high heterogeneity in the baseline conditions of patients. Consequently, different studies employing the same methods can reach discrepant conclusions. Several reviews and meta-analyses have demonstrated that pharmacotherapy and psychotherapy remain the first-line treatment options for depression following TBI (Salter et al., 2016; Waldron et al., 2013; Yue et al., 2017), while another review examined the use of non-drug treatments, including psychological and electrophysiological interventions (Gertler et al., 2015). However, other treatments have yet to be considered by reviews, and none has presented all possible methods, including pharmacotherapy and non-pharmacotherapy interventions of treating post-TBI depression.
Here, we discussed the possible association between TBI and depression, and reviewed the literature to elaborate on what has been elucidated thus far concerning the different possible treatments for depression following TBI. The information regarding the treatments we gathered and discussed herein will help researchers and clinical doctors to approach this intractable disease more optimally and resourcefully. Our review firstly considers the existence of an association between TBI and depression, and then discusses pharmacotherapy and non-pharmacotherapy interventions. Non-pharmacotherapy-based treatments was further divided into psychological interventions and other interventions (Fig. 1).
Section snippets
Association between TBI and depression
Traumatic brain injury has been proposed to be a risk factor for the development of depression and subsequent illnesses. Morbidity of depression after TBI is reportedly elevated relative to non-TBI cohorts, even at 15 years following the injury event (Hawthorne et al., 2009). Research has provided evidence for an association between TBI and depression as well as other neurological and psychiatric diseases such as anxiety and cognitive dysfunction (Maller et al., 2014a; Perry et al., 2016).
Pharmacological interventions
A summary of pharmacological interventions can be found in Table 1.
Psychological interventions
A summary of psychological interventions can be found in Table 2.
Other interventions
A summary of other interventions can be found in Table 3.
Comparison of pharmacological and non-pharmacological interventions
The current literature indicates that several antidepressants are available, with selective serotonin reuptake inhibitors especially sertraline being the most widely used in the treatment of depression following TBI. However, the efficacy of antidepressants is consistently reduced and treatment-resistance is more common in post-TBI depressive patients than general people due to the complexity of pathology as well as adverse effects and high dropout rates. While some non-pharmacological
Conclusion
After searching the literature for research on the pathology and treatment of post-TBI depression, we concluded that the pathology of depression following TBI is much more complicated than that in general population. Most investigations concerning its treatment have considered pharmacotherapeutic approaches, while psychological interventions have been studied to a lesser extent, and a relatively small proportion of the literature has focused on other treatment modalities: transcranial magnetic
Author contributions
QQL and RJC wrote the manuscript. RL, WRQ YW and BJL provided the critical revisions. All authors approved the final version of the manuscript for submission.
Declaration of competing interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgements
This work was supported by NSFC (grants from the Natural Science Foundation of China 31971078, 81871070, 81971276 and 81901365), Jilin Science and Technology Agency funding (20180519003JH, 20190701078GH and 20180414050GH) and Program for JLU Science and Technology Innovative Research Team.
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