Pharmacological and non-pharmacological interventions of depression after traumatic brain injury: A systematic review

https://doi.org/10.1016/j.ejphar.2019.172775Get rights and content

Abstract

Individuals with traumatic brain injury (TBI) manifest a high incidence of depression, which is associated with an impaired recovery from TBI and a lower quality of life. Several neurobiological changes in patients with TBI contribute a form of depression that is unique to that of general depression. This is evinced by the poor efficacy of antidepressants in treating post-TBI depression relative to general depression. In general, however, the treatment of post-TBI depression has received relatively scattered attention in the literature. The purpose of this review is thus to discuss about the possible pathology of depression following TBI and summarize the recent findings on the treatment of it in clinical studies. While both pharmacological and non-pharmacological approaches can reportedly attenuate depressive symptoms in patients with TBI to a moderate extent, the various limitations of such studies require that further well-powered, randomized controlled trials with larger sample sizes and longer follow-ups are warranted to investigate the exact pathophysiology underlying post-TBI depression, the mechanism underlying treatment efficacy, and the optimal pharmacological and non-pharmacological interventions for this population. A combination of different treatments in a comprehensive therapeutic regimen may be an optimal direction for future research.

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.

References (136)

  • K. Fassbender et al.

    Temporal profile of release of interleukin-1beta in neurotrauma

    Neurosci. Lett.

    (2000)
  • J.R. Geddes et al.

    Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review

    Lancet

    (2003)
  • J. Gill et al.

    Lower health related quality of life in U.S. military personnel is associated with service-related disorders and inflammation

    Psychiatry Res.

    (2014)
  • S. Guetin et al.

    The effect of music therapy on mood and anxiety-depression: an observational study in institutionalised patients with traumatic brain injury

    Ann. Phys. Rehabil. Med.

    (2009)
  • J.M. Hoffman et al.

    A randomized controlled trial of exercise to improve mood after traumatic brain injury

    Pharm. Manag. PM R

    (2010)
  • A. Hudak et al.

    Brain morphometry changes and depressive symptoms after traumatic brain injury

    Psychiatry Res.

    (2011)
  • R.E. Jorge et al.

    Mood disorders after TBI

    Psychiatr. Clin. N. Am.

    (2014)
  • R.E. Jorge et al.

    Depression following traumatic brain injury: a 1 year longitudinal study

    J. Affect. Disord.

    (1993)
  • D.L. Kaelin et al.

    Methylphenidate effect on attention deficit in the acutely brain-injured adult

    Arch. Phys. Med. Rehabil.

    (1996)
  • Y. Kamisaki et al.

    Presynaptic inhibition by clonidine of neurotransmitter amino acid release in various brain regions

    Eur. J. Pharmacol.

    (1992)
  • A.E. Kline et al.

    The selective 5-HT(1A) receptor agonist repinotan HCl attenuates histopathology and spatial learning deficits following traumatic brain injury in rats

    Neuroscience

    (2001)
  • A. Kupferberg et al.

    Social functioning in major depressive disorder

    Neurosci. Biobehav. Rev.

    (2016)
  • A.M. Leaver et al.

    Modulation of intrinsic brain activity by electroconvulsive therapy in major depression. Biological psychiatry

    Cogn. Neurosci. Neuroimaging

    (2016)
  • G.M. Leggio et al.

    Dopamine D(3) receptor as a new pharmacological target for the treatment of depression

    Eur. J. Pharmacol.

    (2013)
  • X. Liu et al.

    Microglia and CNS interleukin-1: beyond immunological concepts

    Front. Neurol.

    (2018)
  • J.J. Maller et al.

    Volumetrics relate to the development of depression after traumatic brain injury

    Behav. Brain Res.

    (2014)
  • D.K. Menon et al.

    Position statement: definition of traumatic brain injury

    Arch. Phys. Med. Rehabil.

    (2010)
  • R.D. Mouradian et al.

    Noradrenergic potentiation of excitatory transmitter action in cerebrocortical slices: evidence for mediation by an alpha 1 receptor-linked second messenger pathway

    Brain Res.

    (1991)
  • P.M. Plenger et al.

    Subacute methylphenidate treatment for moderate to moderately severe traumatic brain injury: a preliminary double-blind placebo-controlled study

    Arch. Phys. Med. Rehabil.

    (1996)
  • K. Abe et al.

    Traumatic brain injury decreases serotonin transporter expression in the rat cerebrum

    Neurol. Res.

    (2016)
  • J.S. Albrecht et al.

    Patterns of depression treatment in medicare beneficiaries with depression after traumatic brain injury

    J. Neurotrauma

    (2015)
  • Y. Alway et al.

    A prospective examination of Axis I psychiatric disorders in the first 5 years following moderate to severe traumatic brain injury

    Psychol. Med.

    (2016)
  • A. Ansari et al.

    Role of sertraline in posttraumatic brain injury depression and quality-of-life in TBI

    Asian J. Neurosurg.

    (2014)
  • T.A. Ashman et al.

    Psychiatric challenges in the first 6 years after traumatic brain injury: cross-sequential analyses of Axis I disorders

    Arch. Phys. Med. Rehabil.

    (2004)
  • T. Ashman et al.

    Comparison of cognitive behavioral therapy and supportive psychotherapy for the treatment of depression following traumatic brain injury: a randomized controlled trial

    J. Head Trauma Rehabil.

    (2014)
  • C. Baeken et al.

    Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neurocircuitry in unipolar depression

    Dialogues Clin. Neurosci.

    (2011)
  • R.A. Bakay et al.

    Pathophysiology of cerebrospinal fluid in head injury: Part 1. Pathological changes in cerebrospinal fluid solute composition after traumatic injury

    Neurosurgery

    (1986)
  • L.A. Baker-Price et al.

    Weak, but complex pulsed magnetic fields may reduce depression following traumatic brain injury

    Percept. Mot. Skills

    (1996)
  • L. Baker-Price et al.

    Intermittent burst-firing weak (1 microTesla) magnetic fields reduce psychometric depression in patients who sustained closed head injuries: a replication and electroencephalographic validation

    Percept. Mot. Skills

    (2003)
  • S. Barker-Collo et al.

    Treatment for depression following mild traumatic brain injury in adults: a meta-analysis

    Brain Inj.

    (2013)
  • M. Bedard et al.

    Mindfulness-based cognitive therapy: benefits in reducing depression following a traumatic brain injury

    Adv. Mind Body Med.

    (2012)
  • M. Bedard et al.

    Mindfulness-based cognitive therapy reduces symptoms of depression in people with a traumatic brain injury: results from a randomized controlled trial

    J. Head Trauma Rehabil.

    (2014)
  • H. Blake et al.

    Exercise intervention in brain injury: a pilot randomized study of Tai Chi Qigong

    Clin. Rehabil.

    (2009)
  • J.A. Blumenthal et al.

    Exercise and pharmacotherapy in the treatment of major depressive disorder

    Psychosom. Med.

    (2007)
  • C.N. Bodnar et al.

    Depression following a traumatic brain injury: uncovering cytokine dysregulation as a pathogenic mechanism

    Neural Regen. Res.

    (2018)
  • C.H. Bombardier et al.

    Rates of major depressive disorder and clinical outcomes following traumatic brain injury

    J. Am. Med. Assoc.

    (2010)
  • P. Cassano et al.

    Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis

    Neurophotonics

    (2016)
  • L.C. Chang et al.

    The emerging use of ketamine for anesthesia and sedation in traumatic brain injuries

    CNS Neurosci. Ther.

    (2013)
  • J.K. Chen et al.

    Neural substrates of symptoms of depression following concussion in male athletes with persisting postconcussion symptoms

    Arch. Gen. Psychiatr.

    (2008)
  • H.A. Croft et al.

    Efficacy and safety of vilazodone in major depressive disorder: a randomized, double-blind, placebo-controlled trial

    J. Clin. Psychiatry

    (2014)
  • Cited by (6)

    View full text