Suicide is a rare but devastating outcome post traumatic brain injury (TBI). However, death by suicide is only the tip of the iceberg, as much larger numbers of people with TBI make suicide attempts or report suicidal ideation. Historically, suicides after TBI were first documented among brain-injured Veterans from the First and Second World Wars (e.g., Russell, Reference Russell1951). Early reports of civilian suicides were contained in broader TBI outcome studies conducted in the United Kingdom and Europe (e.g., Heiskanen & Sipponen, Reference Heiskanen and Sipponen1970; Lewin, Marshall, & Roberts, Reference Lewin, Marshall and Roberts1979). Since then, continued efforts to empirically investigate the prevalence of suicide and the impact of TBI on suicide risk have contributed to a growing body of literature on suicide-related outcomes among TBI survivors. Although studies examining prevalence of suicidal ideation, behaviour and death by suicide among TBI survivors have yielded variable rates, some studies have shown that, compared to the general population, those with a history of TBI are at increased risk of suicidal ideation (Anstey et al., Reference Anstey, Butterworth, Jorm, Chistensen, Rodgers and Windsor2004), suicide attempts (Silver, Kramer, Greenwald, & Weissman, Reference Silver, Kramer, Greenwald and Weissman2001) and death by suicide (Teasdale & Engberg, Reference Teasdale and Engberg2001). However, not all studies have found such a relationship, with two mortality studies not reporting an elevated rate of suicide deaths (Harrison-Felix, Whiteneck, DeVivo, Hammond, & Jha, Reference Harrison-Felix, Whiteneck, DeVivo, Hammond and Jha2006; Shavelle, Strauss, Whyte, Day, & Yu, Reference Shavelle, Strauss, Whyte, Day and Yu2001).
The purpose of this study was to conduct a systematic review of the literature in order to evaluate the evidence regarding prevalence and risk of suicidal thoughts, behaviours and death by suicide following TBI, and to examine the effectiveness of interventions to reduce suicide-related outcomes in those with TBI. The first dedicated review addressing the prevalence of suicidal thoughts and behaviours (deaths and attempts), risk factors for suicide and clinical management approaches among survivors of TBI was published in 2007 (Simpson & Tate, Reference Simpson and Tate2007). A scoping methodology was chosen to ascertain both the breadth and depth of evidence within the field. The structured review identified 48 peer-reviewed journal articles published before 2007 that addressed suicidality among survivors of TBI. This relatively large number of citations was deceptive, however, as few of the articles comprised suicide-specific studies per se. In the majority of cases, suicidal behaviours were incidental to the primary focus of the studies, which were investigating general post-injury mortality, psychosocial outcomes or depression.
Based on the most robust studies available (three population studies, one meta-analysis), the review concluded that, in comparison to the general population, individuals with TBI were at a 3.5–4 times greater risk of suicide (Harris & Barraclough, Reference Harris and Barraclough1997; Teasdale & Engberg, Reference Teasdale and Engberg2001); had a significantly higher lifetime history of suicide attempts (8.1% in TBI survivors versus 1.9% in the general population; Silver et al., Reference Silver, Kramer, Greenwald and Weissman2001) and higher levels of suicidal ideation (Anstey et al., Reference Anstey, Butterworth, Jorm, Chistensen, Rodgers and Windsor2004). The studies into suicide attempts and suicide ideation found that the elevated rates remained significant after adjusting for a range of demographic, socio-economic, psychosocial and psychopathological covariates.
Furthermore, the 2007 review found evidence for two domains of risk factors that modulated levels of suicidal behaviours. Importantly, the following findings were all derived from multivariate analyses that controlled for covariates, including sex, age at injury, time post-injury, length of post-traumatic amnesia, pre-morbid psychiatric disturbance and post-injury psychopathlogy. The first domain was injury severity. People with severe TBI were 1.4 times more likely to die by suicide than people with mild injuries (95% confidence interval (CI), 1.15, 1.75; Teasdale & Engberg, Reference Teasdale and Engberg2001). The second domain was post-injury psychopathology. Post-injury substance abuse, suicide ideation, hopelessness and/or the presence of any post-injury psychiatric history/emotional distress were significant predictors of either suicide attempts or suicide ideation (Simpson & Tate, Reference Simpson and Tate2002, Reference Simpson and Tate2005; Teasdale & Engberg, Reference Teasdale and Engberg2001). The risk of attempts or suicidal ideation among individuals with such psychopathology was 4.9–8.7 times greater than for people with TBI and no post-injury history of psychopathology (Simpson & Tate, Reference Simpson and Tate2002, Reference Simpson and Tate2005; Teasdale & Engberg, Reference Teasdale and Engberg2001). The review also found that among TBI survivors, little research into suicide prevention had been conducted. No treatments or clinical management approaches for people with TBI had been tested. The only experimental report was of the outcomes from a controlled trial of a suicide prevention training programme delivered to rehabilitation and disability staff working in the field of TBI (Simpson, Winstanley, & Bertapelle, Reference Simpson, Winstanley and Bertapelle2003).
Overall, the review found a consistent picture of elevated suicidal behaviours after TBI, but the underlying evidence-base was limited to a small number of studies. In the introduction to a recent special issue on suicide and TBI, Simpson and Brenner (Reference Simpson and Brenner2011) observed that there had been an upsurge in research activity in this field over the previous decade. Since the original 2007 review, several narrative reviews of the suicide literature focusing on TBI among civilians and/or military Veterans have been published (Brenner, Vanderploeg, & Terrio, Reference Brenner, Vanderploeg and Terrio2009; Reeves & Brister, Reference Reeves, Brister, Sher and Vilens2009; Reeves & Laizer, Reference Reeves and Laizer2012; Simpson & Tate, Reference Simpson, Tate, Sher and Vilens2009; Wasserman et al., Reference Wasserman, Shaw, Vu, Ko, Bollegala and Bhalerao2008). These reviews have canvassed much of the earlier literature, but have also highlighted a number of newer studies.
Therefore, the current review investigated literature published from the beginning of 2007. While certain aspects of the original review (i.e., risk of suicidal outcomes following TBI and clinical management of suicidal behaviours after TBI) have been preserved, the suicide nomenclature and review methodology have been updated to reflect contemporary developments. The latest standardised suicide nomenclature (the Self-Directed Violence Classification System; Brenner et al., Reference Brenner, Breshears, Betthauser, Bellon, Holman, Harwood and Nagamoto2011b) has been adopted, replacing the 1996 framework (O'Carroll et al., Reference O'Carroll, Berman, Maris, Moscicky, Tanney and Silverman1996) employed in the 2007 study. With respect to methodology, the current review has been conducted in accordance with relevant items from the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement (Liberati et al., Reference Liberati, Altman, Tetzlaff, Mulrow, Gøtzsche, Ioannidis and Moher2009; Moher, Liberati, Tetzlaff, Altman, & the PRISMA Group, Reference Moher, Liberati, Tetzlaff and Altman2010). Items included in the PRISMA statement reflect several conceptual and practical advances in the science of conducting systematic reviews (Moher et al., Reference Moher, Liberati, Tetzlaff and Altman2010), a number of which pertain to assessment of risk of bias.
Despite the centrality of risk of bias assessment in evaluating the strength of evidence in systematic reviews, there is little consensus on the best approach or preferred tool for assessing risk of bias. Given that the current review was designed to address multiple research questions pertaining to TBI and suicide-related outcomes, approaches and tools selected would need to take into account the heterogeneity of studies both with respect to design and study conduct. In the absence of a gold-standard tool for assessing risk of bias across different types of studies, a number of different potential tools and approaches were considered for the current review. The two tools finally selected to rate the study designs targeted in this review, namely, the Research Triangle Institute (RTI) Risk of Bias tool (Viswanathan & Berkman, Reference Viswanathan and Berkman2012) for observational studies and the PEDro rating scale (Sherrington, Herbert, Maher, & Moseley, Reference Sherrington, Herbert, Maher and Moseley2000) for randomised trials, met many of the recommended criteria for risk of bias measurement selection (Reeves, Deeks, Higgins, & Wells, Reference Reeves, Deeks, Higgins, Wells, Higgins and Green S2008; Viswanathan et al., Reference Viswanathan, Ansari, Berkman, Chang, Hartling, McPheeters and Treadwell2012). Specifically, they were designed for use in systematic reviews; demonstrated acceptable reliability and validity; provided explicit support for judgements; were easy to use; addressed items related to different sources of bias (i.e., study level and outcome level); avoided the use of uniform weights across items (RTI Risk of Bias tool only); were specific to the study designs being evaluated; and, when possible, the risk of bias assessment was not presented as a composite score, or if a composite score was used, its validity as an overall measure of methodological quality had been established previously (e.g., PEDro rating scale; deMorton, Reference deMorton2009). Informed by these advances in methodology, the review addressed two key questions (KQ):
KQ1. Among adult survivors of TBI, what is the association between history of TBI and post-TBI death by suicide, suicide attempts or suicidal ideation? KQ1 specifically investigated the prevalence of the suicidal behaviours (i.e., death by suicide, suicide attempts and suicidal ideation) and the extent to which the presence of TBI increased risk for suicidal thoughts and behaviours.
KQ2. What interventions are effective in reducing suicide-related outcomes in adult survivors of TBI?
Methods
The methodology and presentation of results followed the PRISMA Statement for reporting systematic reviews of studies that evaluate healthcare interventions (Liberati et al., Reference Liberati, Altman, Tetzlaff, Mulrow, Gøtzsche, Ioannidis and Moher2009; Moher et al., Reference Moher, Liberati, Tetzlaff and Altman2010). In particular, the research group used PRISMA items 1, 3–4, 6–13, 17–20 and 24–26, and the recommended study flow diagram. Items that were not included were outside the scope of the current review. For example, heterogeneity of methods, study conduct and overall study quality across the relatively small number of studies identified for each key question precluded quantitative synthesis of results. As such, items 14–16 and 21–23 were not reported as they pertain to summary statistics and meta-analyses. Following study selection and data extraction, risk of bias of each outcome of interest within individual studies was assessed and incorporated in a qualitative synthesis of findings from all studies for each key question and outcome.
Search Strategy
PubMed, PsycINFO, EMBASE and the Cochrane Central Register of Controlled Trials (Central) were searched on 1 October 2012 for peer-reviewed articles published in English from 1 January 2007 through 1 October 2012 to gather relevant articles to address the aims examined in the key research questions listed above. Terms relating to suicide and self-directed violence were crossed with terms related to traumatic brain injury (see Table 1). Prior to the search strategy being finalised, preliminary searches across all databases were conducted that included additional self-harm terms from the National Institute for Health and Clinical Excellence (NICE) commissioned report on self-harm (NICE, 2012). Searches were also conducted using additional brain injury terms from the World Health Organisation (WHO) report on mild traumatic brain injury (mTBI) (Carroll, Cassidy, Holm, Kraus, & Coronado, Reference Carroll, Cassidy, Holm, Kraus and Coronado2004). After running the preliminary searches with these additional terms and browsing the results, it was determined by unanimous consensus within the research group that while highly sensitive, the search yield was not specific enough for the purposes of this review. For example, the vast majority of studies that were identified were not specific to TBI, but instead covered a wide range of physical injuries and illnesses throughout the body. Based on these issues, the search terms were further refined to improve detection of TBI-specific studies while filtering out studies that were focused on other types of injury.
TABLE 1 PubMed Search Strategy
Study Selection
Data were exported from each database and abstracted and de-duplicated using EndNote X3 (Build 4094) by a research assistant with experience working on TBI-related research studies. When identifying duplicates in EndNote, records were removed from the count of the database with the lower priority. Databases were assigned priority a priori and results were de-duplicated according to the following priority: EMBASE > PubMed > PsycINFO > CENTRAL. Using a standardised electronic template, all abstracts were reviewed by two ‘blind’ reviewers (L.B. and N.B.) with expertise in TBI and suicide, to determine whether they met inclusion criteria. Studies were included if they were believed to have met the following study characteristics (Population, Intervention, Comparators, Outcomes, Timing, Setting).
Population(s)
This review was focused on adults who experienced TBI. The ‘adult’ age filters were used during the literature search to target studies that included adults. For PubMed, adults were defined as age 19 and above. For PsycINFO and EMBASE, adults were defined as age 18 and above. Studies that did not differentiate between adult and child populations were excluded. A clear case definition for TBI must also have been provided.
Intervention(s)
Randomised and non-randomised interventions that contribute to suicide prevention and reported a suicide-related outcome.
Comparator(s)
Similar populations that have not been diagnosed with TBI; comparison group was not required for inclusion.
Outcome(s)
Suicidal ideation and/or behaviour as defined according to the Self-Directed Violence Classification System (Brenner et al., Reference Brenner, Breshears, Betthauser, Bellon, Holman, Harwood and Nagamoto2011b), which can be accessed at http://www.mirecc.va.gov/visn19/docs/SDVCS.pdf
Timing
No limitations based on timing.
Setting
No limitations based on study setting.
Additional criteria included: (1) the full-text article was in English; (2) the article addressed a TBI population and measured post-TBI suicide-related outcomes (studies with samples from the general population who suffered a TBI as a result of self-inflicted injury were excluded); (3) the article presented original study data (dissertations, commentaries, editorials, letters, books/book chapters and reviews were excluded); and (4) the study used a quantitative design (qualitative studies were excluded). Although excluded, any systematic reviews and meta-analyses identified were reviewed for additional reference mining. At the abstract review level (PRISMA Screening Stage), disagreements regarding inclusion criteria were resolved by including a third reviewer for consensus.
Full-text was obtained for all articles that met the screening inclusion criteria. Each article was examined by two reviewers (three ‘blind’ reviewers in total taking part). If upon full-text review (PRISMA Eligibility Stage), it was determined that the article did not meet inclusion criteria (as noted above), it was excluded. Disagreements regarding the inclusion of an article at the Eligibility Stage were similarly resolved by consensus of a third reviewer. Reviewers discussed any remaining studies and ultimately reached a unanimous decision regarding the inclusion status of all articles.
Additional searches were conducted of the reference lists of all included articles, systematic reviews and meta-analyses identified in the literature search, as well as the grey literature (using Google Search and Google Scholar). For the grey literature, an advanced search was conducted searching for all of the words ‘traumatic brain injury’ and ‘suicide’. The first 11 pages of results were reviewed for possible inclusion according to the same criteria as the database literature search. Any review articles identified in these searches were also mined for additional references.
Data Abstraction
The following data were abstracted for observational studies with prevalence of suicidal ideation (SI), suicide attempt (SA) or both as outcome of interest: study design, sample size and setting, sample demographics (sex, age), TBI severity, source or measure of SI/SA, and time frame, time post-injury and prevalence of SI/SA. For observational studies that investigated whether the presence of TBI increased risk for SI/SA, data abstracted included additional information pertaining to analyses and results. Studies in which death was the outcome of interest abstracted the following: study design, population/sample, study admission (target period), TBI severity, reference population, prevalence of suicide, and standard mortality ratios (SMR) or odds ratios (OR). Data abstracted from treatment studies included: design, sample size and setting, sample demographics (sex, age), TBI severity, time post injury, primary outcomes, measures of SI, attrition and treatment outcome.
Assessment of Risk of Bias of Observational Studies
Procedures and tools for assessing risk of bias for observational studies were largely informed by guidelines established in the Agency for Healthcare Research and Quality methods guide for systematic reviews (Viswanathan & Berkman, Reference Viswanathan and Berkman2012; Viswanathan et al., Reference Viswanathan, Ansari, Berkman, Chang, Hartling, McPheeters and Treadwell2012) and included the procedures described below.
Classification of Study Design
Correct classification of study design and identifying critical sources of bias and confounding for that type of design are critical to accurately assessing risk of bias (Viswanathan & Berkman, Reference Viswanathan and Berkman2012). The design for each study meeting inclusion criteria following full-text review was assessed by two independent raters using the Taxonomy of Study Design Tool (Hartling et al., Reference Hartling, Bond, Harvey, Santaguida, Viswananthan and Dryden2010). Disagreements were discussed until consensus was achieved.
Risk of Bias Components Analysis
For observational studies, the RTI Risk of Bias tool (Viswanathan & Berkman, Reference Viswanathan and Berkman2012) was utilised to assess risk of bias, confounding and precision. Using a components approach, the RTI tool was specifically developed to assess risk of bias across different types of observational studies (i.e., cohort, case-control, cross-sectional and case-series). Sources of bias assessed include selection bias (e.g., differential selection of study participants, inappropriate selection of controls, inclusion/exclusion criteria inconsistently applied within or across groups), detection bias (e.g., inaccurate assessment or misclassification of exposure and outcomes, use of unreliable or poorly validated measures), performance bias (e.g., variations in procedures administered, protocol deviations), reporting bias (i.e., differential or incomplete reporting of outcomes and study findings), attrition bias (e.g., high or differential loss to follow-up), and confounding (e.g., failure to identify or account for important confounders through design or analysis) (Viswanathan et al., Reference Viswanathan, Ansari, Berkman, Chang, Hartling, McPheeters and Treadwell2012). In addition to risk of bias, three additional RTI items rate the precision of findings/estimates in situations where the heterogeneity of findings prevents pooling of data. Detailed instructions for the reviewer and response options pertaining to each of the questions are provided to increase clarity, accuracy and ease of use. In addition to completing response options, reviewers are instructed to provide an explanation for their ratings, thereby increasing the transparency of the evaluation.
Although the RTI Risk of Bias tool is a new tool, its development and refinement were based on a rigorous, multiphase process that consisted of face validity testing, cognitive testing, content validity testing and inter-rater reliability testing. Specifically, inter-rater reliability of the original 40-item measure ranged from 90% for questions concerning presentation and 88% for those concerning soundness of information, to 56% for questions concerning follow-up (Viswanathan & Berkman, Reference Viswanathan and Berkman2012). The items that had poor inter-rater reliability were either removed or revised to improve clarity and usefulness. Following this process, further evaluation and testing of the measure through expert consensus contributed to the refined 16-item measure used in this systematic review.
Prior to evaluating risk of bias for the individual studies, reviewers met and discussed the form to clarify specific criteria pertaining to some of the questions. Decisions were made regarding important confounding variables, measures and indicators of exposure status, and measures considered to be valid and reliable. These criteria and guidelines were added to the review form to help facilitate accuracy and reliability across reviewers.
Each observational study that met inclusion criteria following full-text review was evaluated using RTI items that reflected sources of bias specific to its study design. For example, the number of core items pertaining to each of the observational designs is as follows: case series (8), case-control (8), cohort (12) and cross-sectional (10). Each risk of bias criterion was evaluated using the appropriate criteria for that study design and for each predetermined outcome. Following completion of all items, indications of bias and precision were summarised in a table by category (e.g., selection bias, detection bias). These summary results were used to evaluate the overall risk of bias for the study for each selected outcome.
Global rating of the risk of bias
Global ratings of bias for each study were classified as low (results are valid or represent true effects), moderate (results are valid and/or represent true effect; however, study is susceptible to some bias, but not to the degree that the results would be considered invalid), high (a study with significant flaws and marked by biases of various natures that are likely to invalidate the results) or unknown (missing information which makes it difficult to judge limitations) (Viswanathan et al., Reference Viswanathan, Ansari, Berkman, Chang, Hartling, McPheeters and Treadwell2012). Two reviewers independently assessed risk of bias (individual criteria and global rating). Disagreements were resolved through consensus and, if needed, a third researcher was consulted. As two of the authors of this review were also authors on 6 out of the 16 papers evaluated, individuals were not primarily responsible for review of the articles on which they were authors.
Assessment of Risk of Bias of Randomised Trials
The single randomised clinical trial (RCT) included in this review was independently assessed by two reviewers using the PEDro scale (Sherrington et al., Reference Sherrington, Herbert, Maher and Moseley2000), an 11-item scale designed for rating methodological quality of RCTs. Reliability and validity of the scale has been established across several studies (deMorton, Reference deMorton2009; Macedo et al., Reference Macedo, Elkins, Maher, Moseley, Herbert and Sherrington2010; Maher, Sherrington, Herbert, Moseley, & Elkins, Reference Maher, Sherrington, Herbert, Moseley and Elkins2003). Items address various components related to the conduct of the study and sources of bias that can impact the validity of findings. These include, but are not limited to, randomisation, concealed allocation, blinding, outcome reporting and follow-up/attrition. Each satisfied item (except for item 1) contributes one point to the total PEDro score (range = 0–10 points). A search for the trial was then performed on Psycbite (www.psycbite.com), an extensive database of cognitive, behavioural and other treatments for psychological problems resulting from acquired brain impairment (ABI) and independently rated for their methodological quality (Tate et al., Reference Tate, Perdices, McDonald, Togher, Moseley, Winders and Savage2004). Scores from the current review were compared to the Psycbite PEDro score.
Current standards listed in the PRISMA statement indicate that critical appraisal of studies should consider both study level (e.g., allocation concealment) and outcome level (e.g., reliability and validity of outcome data) sources of bias. Although the PEDro scale incorporates several items that address sources of bias with respect to study-level characteristics (e.g., randomisation, allocation, ‘blinding’ of therapists), the number of items that specifically assess outcome-measurement bias are limited and primarily focused on ‘blinding’ of outcome assessors. Taking this into consideration, information related to measurement bias not explicitly addressed by the PEDro scale (i.e., reliability and validity of measures used to assess exposure and outcomes) was noted and considered in conjunction with PEDro scores when determining the overall risk of bias and quality rating for the trial.
Results
Study Selection
A total of 999 titles and abstracts obtained from the electronic searches were reviewed. Fifteen additional studies were identified from other sources. Applying inclusionary/exclusionary criteria, 83 articles were reviewed (see Figure 1). Of these articles, 67 were excluded as described in Figure 1. Thirteen studies were identified for KQ1 (five deaths, eight ideation and/or attempts) and three treatment-related studies were identified for KQ2.
FIGURE 1 Literature flow diagram.
Study Characteristics and Risk of Bias
Individual study characteristics, indicators of bias and global ratings of bias for individual studies are presented in Tables 2–6.
TABLE 2 Prevalence and Risk of Suicide After TBI
SMR, Standardized Mortality Ratio; OR, Odds Ratio; CI, Confidence Interval; VHA, Veterans Health Administration; TBI, Traumatic Brain Injury; TIH, Traumatic Intracranial Haemorrhage; Mod, Moderate; Sev, Severe; ICD-10, International Statistical Classification of Diseases-10; NP A'x, Neuropsychological Assessment; NR, Not Reported; NA, Not Applicable.
aDetermined using the Taxonomy of Study Design Tool (Hartling et al., Reference Hartling, Bond, Harvey, Santaguida, Viswananthan and Dryden2010).
bRTI Risk of Bias tool (Viswanathan & Berkman, Reference Viswanathan and Berkman2012); potential sources of bias include selection bias (SB), detection bias (DB), performance bias (PB), reporting bias (RB), attrition bias (AB), confounding (CON) and precision (PRE).
cSMR reported as statistically significant but p value not provided.
dInjuries classified as lesions included cerebral contusion and intracranial haemorrhage.
*p <.0001, adjusted model. **p = .0002, adjusted model. †p = .006, adjusted model.
TABLE 3 Prevalence of Suicide Attempts (SA) After TBI
TBI, Traumatic Brain Injury; Mod, Moderate; Sev, Severe; M, Male; F, Female; H'x, History; IP, Inpatient; M, Mean; Mdn, Median; NA, Not Applicable; SD, Standard deviation; yrs, years.
aDetermined using the Taxonomy of Study Design Tool (Hartling et al., Reference Hartling, Bond, Harvey, Santaguida, Viswananthan and Dryden2010).
b RTI Risk of Bias tool (Viswanathan & Berkman, Reference Viswanathan and Berkman2012); potential sources of bias include selection bias (SB), detection bias (DB), performance bias (PB), reporting bias (RB), attrition bias (AB), confounding (CON), and precision (PRE).
TABLE 4 Prevalence of Suicidal Ideation (SI) After TBI
TBI, Traumatic Brain Injury; Mod, Moderate; Sev, Severe; M, Male; F, Female; BDI-II, Beck Depression Inventory-II; M, Mean; SD, Standard deviation; Mdn, Median; H'x History; IP, Inpatient; NA, Not Applicable; yrs, years.
aDetermined using the Taxonomy of Study Design Tool (Hartling et al., Reference Hartling, Bond, Harvey, Santaguida, Viswananthan and Dryden2010).
bRTI Risk of Bias tool (Viswanathan & Berkman, Reference Viswanathan and Berkman2012); potential sources of bias include selection bias (SB), detection bias (DB), performance bias (PB), reporting bias (RB), attrition bias (AB), confounding (CON), and precision (PRE).
TABLE 5 Risk of Suicide Attempts (SA) and/or Suicidal Ideation (SI) After TBI
TBI, Traumatic Brain Injury; M, Male; F, Female; NR, Not Reported; OR, Odds Ratio; M, Mean; SD, Standard deviation; H'x, History; IP, Inpatient; PTSD, Post-traumatic Stress Disorder; PTA, Post-traumatic Amnesia; GCS, Glasgow Coma Scale; BDI-II, Beck Depression Inventory-II; mTBI, mild traumatic brain injury; SCID-I/P, Structured Clinical Interview for DSM-IV (Patient Version); NA, Not Applicable; ns, not significant; yrs, years.
aDetermined using the Taxonomy of Study Design Tool (Hartling et al., Reference Hartling, Bond, Harvey, Santaguida, Viswananthan and Dryden2010).
bRTI Risk of Bias tool (Viswanathan & Berkman, Reference Viswanathan and Berkman2012); potential sources of bias include selection bias (SB), detection bias (DB), performance bias (PB), reporting bias (RB), attrition bias (AB), confounding (CON) and precision (PRE).
*p = .0005
TABLE 6 Treatment Studies
RCT, Randomised Controlled Trial; Mod, Moderate; Sev, Severe; M, Male; F, Female; yrs, years; wks, weeks. T'x, Treatment; GCS, Glasgow Coma Scale; NR, Not Reported; CBT, Cognitive Behavior Therapy; mg, milligram; NSI, Neurobehavioral Symptom Inventory;NS, not significant.
aDetermined using the Taxonomy of Study Design tool (Hartling et al., Reference Hartling, Bond, Harvey, Santaguida, Viswananthan and Dryden2010).
bRTI Risk of Bias tool (Viswanathan & Berkman, Reference Viswanathan and Berkman2012); potential sources of bias include selection bias (SB), detection bias (DB), performance bias (PB), reporting bias (RB), attrition bias (AB), confounding (CON), and precision (PRE).
* p< .05
Synthesis of Evidence
KQ1: Death by Suicide
Death by suicide as an outcome was reported in five studies (Table 2). The purposes of the studies varied. One study specifically examined suicide-related mortality among military Veterans with and without TBI (Brenner, Ignacio, & Blow, Reference Brenner, Ignacio and Blow2011c). Two studies investigated mortality among civilians with TBI and included data on cause-specific deaths, including suicide (Harrison-Felix et al., Reference Harrison-Felix, Whiteneck, Jha, DeVivo, Hammond and Hart2009; Himanen et al., Reference Himanen, Portin, Hamalainen, Hurme, Hiekkanen and Tenovuo2011). Finally, two studies examined individuals with TBI who died by suicide among more broadly defined populations: (1) all suicides in a province of Finland (Mainio et al., Reference Mainio, Kyllonen, Viilo, Hakko, Sarkioja and Rasanen2007); and (2) all suicides among United States serving military (Skopp, Trofimovich, Grimes, Oetjen-Gerdes, & Gahm, Reference Skopp, Trofimovich, Grimes, Oetjen-Gerdes and Gahm2012). Interestingly, the rates of TBI among the general suicide deaths in both studies were very similar (Finish study 5.5%; United States Military study, 7.3%). Three of these studies sought to quantify the level of risk of death by suicide associated with TBI (Brenner et al., Reference Brenner, Ignacio and Blow2011c; Harrison-Felix et al., Reference Harrison-Felix, Whiteneck, Jha, DeVivo, Hammond and Hart2009; Skopp et al., Reference Skopp, Trofimovich, Grimes, Oetjen-Gerdes and Gahm2012), while the other two were descriptive only.
Findings from two retrospective cohort studies (Brenner et al., Reference Brenner, Ignacio and Blow2011c; Harrison-Felix et al., Reference Harrison-Felix, Whiteneck, Jha, DeVivo, Hammond and Hart2009) supported an increased risk for death by suicide among persons with TBI, while results from one case-control study (Skopp et al., Reference Skopp, Trofimovich, Grimes, Oetjen-Gerdes and Gahm2012) did not show a significantly higher rate of TBI among those who died by suicide. Global rating of bias for one of the cohort studies (Brenner et al., Reference Brenner, Ignacio and Blow2011c), was low, and results supported an increased risk for death by suicide among US Veterans with TBI (ranging from 1.3 to 2.0 times higher than Veterans without TBI). Harrison-Felix et al. (Reference Harrison-Felix, Whiteneck, Jha, DeVivo, Hammond and Hart2009) found elevated rates of suicide among a civilian cohort of TBI patients (about three times higher than persons in the general population of similar age, sex and race). However, this study had a moderate risk of bias. Although a number of important known confounders were taken into account, presence of TBI and other health-related risk factors in the comparison group (i.e., US general population) introduced sources of selection bias and other potential confounders. Furthermore, use of national death rates as opposed to general population rates for the State of Colorado also contributed to the moderate rating as age-adjusted suicide rates in the state of Colorado are notably higher than national death rates (Centers for Disease Control and Prevention, 2012). Lastly, using a case-control design, Skopp et al. (Reference Skopp, Trofimovich, Grimes, Oetjen-Gerdes and Gahm2012) compared the profile of mild TBI, psychiatric and relationship status among all 1764 suicides that occurred among serving military in the United States from 2001 to 2009 with a matched control group. The authors did not find a significantly higher rate of mild TBI among the suicide group compared to the controls. This study also had a moderate risk of bias.
KQ1: Suicide Attempts
Two retrospective suicide-specific studies reported the prevalence of suicide attempts as an outcome (Table 3). Both studies conducted archival reviews of the files of Veterans with mixed injury severity (mild to severe) in the chronic phase of TBI (14 years, 15 years). Breshears, Brenner, Harwood and Gutierrez (Reference Breshears, Brenner, Harwood and Gutierrez2010) found that 7.1% of their sample had a post-injury history of a suicide attempt within the two-year study period, with almost half of these individuals having more than one event. Gutierrez, Brenner and Huggins (Reference Gutierrez, Brenner and Huggins2008) identified a case series of 22 Veterans with TBI who had a post-injury history of psychiatric inpatient admissions, with a file review finding reports of suicide attempts among 27.3% (6/22) of the sample. Both studies were classified as having moderate risk of bias.
KQ1: Suicidal Ideation
Two retrospective single-centre studies reported on the prevalence of suicide ideation as an outcome (Table 4). Both were suicide-specific studies, addressing civilian (Tsaousides, Cantor, & Gordon, Reference Tsaousides, Cantor and Gordon2011) and Veteran (Guitierrez et al., Reference Gutierrez, Brenner and Huggins2008) samples. The first study, rated as having a low risk bias, found a 28.3% rate of suicide ideation (item nine on the BDI-II; Beck, Steer, & Brown, Reference Beck, Steer and Brown1996) over the previous two-week period among a large sample of community-dwelling adults with TBI in the chronic phase post-injury. The second study (Gutierrez et al., Reference Gutierrez, Brenner and Huggins2008), rated as having a moderate risk of bias, found a prevalence rate of 72.7% among their sample of individuals who also had a history of post-injury psychiatric hospitalisation.
KQ1: Risk of Suicide Attempts and Suicidal Ideation after TBI
Five heterogeneous studies applied this question to a diverse range of issues (Table 5). Two of the five studies were rated as having a moderate risk of bias (Brenner et al., Reference Brenner, Betthauser, Homaifar, Villarreal, Harwood, Staves and Huggins2011a; Wood, Williams, & Lewis, Reference Wood, Williams and Lewis2010), with the remainder rated as having a high risk of bias. In a controlled prospective cross-sectional suicide-specific study, Wood et al. (Reference Wood, Williams and Lewis2010) reported a 33.3% rate of suicide ideation (item nine on the BDI-II; Beck et al., Reference Beck, Steer and Brown1996) among 90 patients of mixed injury severity. This rate was significantly greater than that reported by a matched comparison group of healthy controls.
Three studies examined the relationship between post-traumatic stress disorder (PTSD), TBI or mild TBI and suicide risk in US Veteran samples. In an archival case-controlled study (moderate risk of bias), Brenner et al. (Reference Brenner, Betthauser, Homaifar, Villarreal, Harwood, Staves and Huggins2011a) examined a sample of Veterans with a history of suicide attempts, and compared them to a matched control group with no such history. The naturally occurring proportion of Veterans with TBI in both groups was high, virtually identical at approximately 30%. In a series of logistic regressions, the relative association of PTSD versus TBI was tested, finding that while a history of PTSD was associated with an increased risk for having a history of suicide attempts, a similar relationship was not found for TBI. Two other studies (Barnes, Walter, & Chard, Reference Barnes, Walter and Chard2012; Romesser et al., Reference Romesser, Shen, Reblin, Kircher, Allen, Roberts and Marchand2011; both high risk of bias) examined whether a comorbid mild TBI among Veterans with PTSD played an additive role, increasing the likelihood of suicidal behaviours, compared to Veterans with PTSD alone. Both studies reported non-significant results. The aim of the final study (Yurgelun-Todd et al., Reference Yurgelun-Todd, Bueler, McGlade, Churchwell, Brenner and Lopez-Larson2011) was to examine the relationship between frontal white matter systems and measures of impulsivity and suicidality in Veterans with TBI. Descriptive data regarding SI were also reported. Risk of bias was moderate.
KQ2: Interventions for Reducing Suicide-related Outcomes in Persons with TBI
Three treatment studies (two psychosocial, one pharmacological) were identified in which suicide ideation was an outcome (Table 6). However, suicide ideation was not the primary target of any of the three treatments. One study specifically aimed to reduce suicide risk by treating hopelessness. It was the only study which tested an a priori hypothesis pertaining to suicide ideation. The study's primary hypothesis was that a psychological treatment would reduce hopelessness after severe TBI (primary outcome). The study also hypothesised that this reduction in hopelessness would be associated with a related reduction in suicide ideation (a secondary outcome), due to the intercorrelation between the two clinical phenomena. This hypothesis was tested in a RCT (Simpson, Tate, Whiting, & Cotter, Reference Simpson and Brenner2011; low risk of bias). Although the suicide ideation scores decreased from pre- to post-intervention among the treatment group while scores of the waiting list group members increased (suggesting increased ideation), these trends were non-significant.
The other two studies were rated as an unclear risk (Rapoport et al., Reference Rapoport, Chan, Lanctot, Herrmann, McCullagh and Feinstein2008) and high risk of bias (Rees & Bellon, Reference Rees and Bellon2007). In both studies, changes in suicidal ideation were incidental to the primary treatment target (depression, Rapoport et al., Reference Rapoport, Chan, Lanctot, Herrmann, McCullagh and Feinstein2008; post-concussional symptoms, Rees & Bellon, Reference Rees and Bellon2007) and were reported along with other symptoms on depression measures.
Discussion
The World Health Organisation asserts that suicide is preventable (World Health Organisation, 2012). One application of this principle at an organisational level is to ensure that sufficient knowledge regarding those at risk is available to guide resource allocation (e.g., research, clinical). The current review identified 16 studies that addressed the issue of suicide after TBI, of which three had a low risk of bias. These three studies investigated different indicators of self-directed violence among those with TBI as their primary aim. Two of the studies addressed the associations between TBI and suicide deaths (Brenner et al., Reference Brenner, Ignacio and Blow2011c) or suicidal ideation (Tsaousides et al., Reference Tsaousides, Cantor and Gordon2011). The third was an RCT of a suicide prevention treatment (Simpson et al., Reference Simpson, Tate, Whiting and Cotter2011). Nine of the remaining studies were determined to have a moderate risk of bias, with the final four being rated as having high or unclear levels of bias.
The review found new robust evidence of the association between TBI and elevated risk of suicide. The report by Brenner et al. (Reference Brenner, Ignacio and Blow2011c) was the first suicide-specific study among Veterans with TBI since Achte, Lonnqvist and Hillbom's (Reference Achte, Lonnqvist and Hillbom1971) seminal work reporting on Second World War Finish Veterans. This elevated rate among Veterans was also reported in the meta-analysis by Harris and Barraclough (Reference Harris and Barraclough1997) and complements the findings from the civilian population study by Teasdale and Engberg (Reference Teasdale and Engberg2001). The elevated rate of suicide was also found in a single-centre study investigating mortality among a rehabilitation cohort (Harrison-Felix et al., Reference Harrison-Felix, Whiteneck, Jha, DeVivo, Hammond and Hart2009; moderate risk of bias).
These two positive findings contribute to the debate about whether there is an elevated risk of suicide after TBI. Some studies have not found a significant association (e.g., Harrison-Felix, Whiteneck, DeVivo, Hammond, & Jha, Reference Harrison-Felix, Whiteneck, DeVivo, Hammond and Jha2004; Lewin et al., Reference Lewin, Marshall and Roberts1979; Shavelle et al., Reference Shavelle, Strauss, Whyte, Day and Yu2001). However, Harrison-Felix et al. (Reference Harrison-Felix, Whiteneck, DeVivo, Hammond and Jha2004) have raised the issue that findings based on small numbers of suicides (e.g., one or two) need to be viewed with caution because the corresponding standardised mortality ratios are too unstable. Given the low base rate of suicide (typically 1–2 per 10,000), studies investigating death by suicide need to be adequately powered. As such, large-scale studies are required to address meaningfully this question. Interestingly, the large-scale studies conducted to date have all found evidence of increased suicide risk.
In addition to issues of statistical power, selection of an appropriate comparison group is one of the most critical aspects in the design of a cohort study. Understanding the true effect of TBI on suicidal outcomes requires selection of a comparison group that is similar to the exposed TBI cohort on all important characteristics except for TBI status. Of the three retrospective cohort studies, only one (Brenner et al., Reference Brenner, Ignacio and Blow2011c) used a comparison group of persons without a history of TBI that were selected from the same source population as those with TBI, while the other two (Harrison-Felix et al., Reference Harrison-Felix, Whiteneck, Jha, DeVivo, Hammond and Hart2009; Himanen et al., Reference Himanen, Portin, Hamalainen, Hurme, Hiekkanen and Tenovuo2011) relied on external comparison groups (i.e., general population rates) to examine the effect of TBI on overall mortality or death by suicide. Although convenient, use of external comparison groups limits understanding of the true effects of TBI on suicide outcomes. Even if the general population is chosen to be as similar as possible to the TBI cohort in relation to basic demographic and geographic variables, presence of TBI and other unidentified risk factors in the comparison group may lead to either an underestimation or overestimation of its true effect.
Despite the upsurge of research activity in the area of TBI and suicide in the past 5 years, there continues to be a dearth of quality research examining the prevalence of suicidal ideation and attempts among those with TBI. Most notably, since the first review (Simpson & Tate, Reference Simpson and Tate2007), no new population-level studies investigating ideation or attempts among those with TBI were identified. At the level of clinical studies, the 28.3% prevalence rate of suicide ideation found by Tsaousides et al. (Reference Tsaousides, Cantor and Gordon2011; low risk of bias) was similar to rates reported in the three studies identified in the 2007 review. Together, the four studies all highlight significant levels of suicide ideation present in the chronic phase post-TBI. The one study employing a non-brain-damaged (healthy) control group found that the rate of suicide ideation among people with TBI was significantly higher (Wood et al., Reference Wood, Williams and Lewis2010; moderate risk of bias).
A new development in this review was the emergence of studies that examined whether the increased risk of suicide identified in TBI samples/populations could be detected among the general population or other clinical groups (i.e., PTSD). Two studies examined suicide deaths (Skopp et al., Reference Skopp, Trofimovich, Grimes, Oetjen-Gerdes and Gahm2012) and suicide attempts (Brenner et al., Reference Brenner, Betthauser, Homaifar, Villarreal, Harwood, Staves and Huggins2011a) among active duty and Veteran populations. Using a case-control methodology (suicidal behaviour present versus absent), they investigated whether a greater proportion of cases in the suicide-present groups had a history of TBI. Neither of these studies found that TBI was a significant risk factor. Similarly, the two studies which examined whether the presence of co-morbid TBI in Veterans with PTSD added to the level of suicidal ideation (Barnes et al., Reference Barnes, Walter and Chard2012; Romesser et al., Reference Romesser, Shen, Reblin, Kircher, Allen, Roberts and Marchand2011) were also non-significant. Potential reasons for these non-significant findings include study design, the low-base rate of suicidal behaviour, small sample sizes, and/or dependence on chart review for data regarding exposure (TBI) and outcomes (suicidal thoughts or behaviours).
The review identified one RCT (Simpson et al., Reference Simpson, Tate, Whiting and Cotter2011), a psychological treatment for hopelessness among people with severe TBI. Although the intervention did not directly target a suicidal behaviour, hopelessness is one of the strongest predictors of suicide and is closely correlated with suicide ideation. Despite this advance, the treatment still requires replication in larger trials of high-quality design.
Overall, the studies displaying moderate or high risk of bias varied significantly in terms of methodology and assessment of TBI. Many did not use psychometrically sound tools to measure outcomes of interest. Few studies adjusted the results for the most important potential confounding factors (i.e., age and gender) contributing to significant sources of bias. The variability noted in terms of both exposure and case ascertainment of TBI and controls further calls into question the strength of existing evidence. Moreover, few new studies were identified wherein suicidal ideation, attempts or death were examined as primary outcomes in TBI-specific samples designed to address the association between TBI exposure and suicidal outcomes. Some of the studies reviewed were notable for their poor reporting of methods and procedures. This lack of transparency made it difficult to rate bias and/or to determine the strength of the existing evidence pertaining to Key Questions 1 and 2. As such, researchers are encouraged to follow reporting guidelines specific to their study design (e.g., STROBE (von Elm et al., Reference von Elm, Altman, Egger, Pocock, Gøtzsche and Vandenbroucke2008) for observational studies).
Some limitations of this review should be considered in interpreting the results. Three additional studies addressing TBI and suicide were identified; however, they did not meet review inclusion criteria (McMillan & Teasdale, Reference McMillan and Teasdale2007; McMillan, Teasdale, Weir, & Stewart, Reference McMillan, Teasdale, Weir and Stewart2011; Ventura et al., Reference Ventura, Harrison-Felix, Carlson, Diguiseppi, Gabella, Brown and Whiteneck2010). In all three, findings regarding those younger than age 18 were mixed with adult data; thereby precluding separate evaluation regarding the results of interest. An inherent limitation of such high specificity is the possibility of excluding quality studies that do not fit within the predetermined parameters, but may otherwise be important contributions to the body of evidence. Additionally, it is important to note that two of the authors of the current review were also authors on 6 of the 16 papers reviewed. As such, various procedures were implemented throughout the systematic review process to reduce biases and ensure objectivity when critically appraising studies. Furthermore, individuals were not primarily responsible for review of the articles on which they were authors.
Findings from this review highlight the need for further research to establish the prevalence of SI and SA among those with a history of TBI. Understanding the true prevalence of these outcomes in TBI populations will support validation of suicide-related outcome measures, and ultimately allow for accurate assessment of change in interventional trials. Moreover, knowledge regarding the prevalence of SI and SA will highlight the resources needed to care for members of this population who, according to the data, are at risk of dying by suicide.
Although the question of increased risk of suicide-related outcomes following TBI was addressed in the current review, specific factors that contribute to increased risk of these outcomes were not examined. Future systematic reviews are also needed to clarify the existing evidence regarding risk and protective factors, as well as warning signs for suicidal thoughts and behaviours among those with TBI. In addition, no reviews have been completed in the aim of establishing evidence-based assessment strategies regarding suicide risk.
Research examining the impact of TBI severity on suicide risk is another area that warrants further investigation. Although studies have shown an increased risk of suicide across all levels of TBI severity, the extent to which TBI severity influences the pathway to suicidal behaviour or the trajectory of risk has yet to be examined extensively. Along these lines, research examining neurobiological correlates and markers of suicide-related outcome among TBI survivors (e.g., Yurgelun-Todd et al., Reference Yurgelun-Todd, Bueler, McGlade, Churchwell, Brenner and Lopez-Larson2011), and the influence of TBI severity on such markers, represent an emerging area of research that holds great potential for advancing the field.
