Discussion
To our knowledge, this study is the first to investigate the relationship between pre-existing depression and mortality, LOS, ICU LOS, or operative intervention after major trauma, as defined by ISS >15. A history of depression was associated with a reduced OR for mortality in our study, which matched for comorbidities, age, gender, injury severity, and GCS score. However, depression was associated with significantly longer stay in hospital and ICU.
Our data are in contrast to studies in non-trauma populations which generally associate depression with increased mortality.26 However, two studies of orthopedic trauma patients have also reported reduced mortality in patients with depression.17 20 Our LOS findings are in keeping with prior evidence that identified depression as a risk factor for LOS and ICU LOS.15–17 19 Increased LOS in hospital and ICU may reflect impaired functional recovery, which is also in keeping with previous reports that patients who develop depression after injuries have impaired long-term functional recovery.7 27 Since long ICU stays may be associated with increased complication rates,28 and poorer long-term morbidity and mortality,29 a history of depression should serve as an important prognostic indicator and might alert clinicians to anticipate the requirement for additional support with rehabilitation.
Depression is also associated with increased perception of pain,30 which may impair patients’ ability to mobilize and engage with physical therapy,31 possibly contributing to this impaired functional recovery and delayed discharge.31 32 There is also evidence that patients with depression are more likely to have poorer health behaviors, such as smoking and physical inactivity,33 which may predispose them to complications and increased LOS.34 Thus, the influence of pain perception and health behaviors on the functional recovery of trauma patients with depression warrants further investigation.
It is common for trauma patients to develop new depressive symptoms when admitted to ICU,35 and trauma patients are at high risk of delirium during both hospital and ICU stays.36 It seems likely that the impact of ICU stays on mental health may be greater for patients with pre-existing mental health difficulties and may therefore require more prolonged management. These patients may require additional input from other services including psychiatry, psychology, and occupational health to support their onward recovery. Although this prolonged multidisciplinary care would increase LOS, this may contribute to the improved mortality observed in this study, since a multidisciplinary approach to care may improve mortality among critically ill patients.37 The effect of a multidisciplinary approach to trauma is an important area of research and interventional studies are needed to investigate the effect on mortality and functional recovery.
There is a possible biological mechanism for the associations observed in this study. It is increasingly recognized that the immuno-inflammatory response plays an important role in trauma.38 A deranged inflammatory response may result in potentially fatal complications such as multiple organ failure and adult respiratory distress syndrome.39 In depression, there is an increase in proinflammatory cytokines as well as changes to the hypothalamic–pituitary–adrenal axis.40 Indeed, when Weinberg et al14 identified increased postoperative complication rates in orthopedic trauma populations, it was suggested that this may have been the result of an increased acute inflammatory response. However, our finding of reduced mortality in patients with depression does not support this hypothesis and it is possible that more complex differences in the acute inflammatory response may contribute to the outcomes observed in this study. Differences in the inflammatory response to trauma in patients with depression must be assessed in further prospective studies. Such research may have implications for all major trauma patients as identifying possible pathways for immuno-inflammatory modulation and could help produce novel treatment options.
Patients with pre-existing depression in our cohort were more likely to undergo operative intervention. It has been demonstrated in non-trauma populations that low self-efficacy can predict reduced participation in treatment decision making,41 as well as poorer long-term surgical outcomes.42 Considering that depression is associated with low self-efficacy,43 44 the increase in operative intervention may be driven by differences in how patients with depression consider and communicate their treatment preferences to clinicians. However, it is not clear from our data whether the differences in operative intervention are due to different patterns of injury, differences in clinicians’ propensity to operate, or patients’ willingness or capacity to consent to surgery. Nonetheless, in orthopedic trauma, patients with depression are more likely to have postoperative complications14; therefore, it is important that further investigations are undertaken to explore why these patients underwent surgical intervention more frequently.
The 6% of patients identified in our study cohort with a pre-existing diagnosis of depression is likely to be lower than the true population prevalence.2 3 The underidentification of patients with depression in trauma has also been reported by other studies, with one study suggesting that 30.2% of depression diagnoses have been missed during patient assessment.14 Since the true prevalence of depression was likely underdiagnosed in the current study, there may be some selection bias according to how detailed a history was available during initial presentation. In trauma, a thorough history may prevent missed injuries which would otherwise increase mortality if left undiagnosed.45 Additionally, knowledge of previous medications and comorbidities is important for guiding appropriate treatment. It is unknown whether the quality of the clinicians’ history might have influenced the results and there is a paucity of literature examining the effect of accurate history taking on trauma mortality. Moreover, although depression is recorded by TARN, it may not be asked about routinely by the treating clinician. Therefore, investigation is needed to identify whether inclusion of depression as a predefined field within prehospital or ED proformas can enable better identification of these patients and whether this may improve patients’ outcomes.
The effect of antidepressant medication on patients’ outcomes is currently an area of debate. Whereas some studies suggest that antidepressants may increase surgical complications,46 others suggest that this is probably mediated by depression itself rather than the antidepressant medications.47 For orthopedic trauma patients, Weinberg et al14 reported that prescribing antidepressant medication to patients with depression did not affect surgical complication rates.14 However, a further study in orthopedic trauma suggested that delays to prescribing antidepressant medication may mediate increased LOS by inducing withdrawal symptoms and preventing effective engagement with therapy.15 In major trauma patients, there is little evidence to suggest whether antidepressant medication affects outcomes. Our study did not investigate antidepressant prescription and it is possible that this may have contributed to the outcomes. Further investigations of the effect of antidepressants in major trauma may help identify the optimum pharmacological management of depression.
Limitations
The most significant limitation of our study methodology is the utilization of a database, with risk of omissions in relevant medical history, including depression. However, TARN is known to be a reliable source of data and is commonly used for similar retrospective cohort studies.21 48 49 Furthermore, it was not possible to assess the severity of a patient’s depression nor how long before the admission they were diagnosed. Additionally, antidepressants may be indicated for other medical conditions and non-pharmacological psychotherapy was not reliably disclosed in clinical records, thus making it impractical to stratify patients based on current treatment. It was therefore not possible to distinguish patients with chronic, well-managed depression from patients with more recent onset, severe or unmanaged depression. Moreover, as previously mentioned, the proportion of patients identified to have depression was lower than expected compared with the UK population. This indicates that some diagnoses of depression are likely to have been missed, which potentially increases the risk of selection bias in this study.
To classify patterns of injury, the mechanisms of injury and AIS scores for each body region were compared between each group. Although there was no significant difference in AIS scores, the groups were not perfectly matched by mechanisms of injury. Although this is an expected limitation of a cohort study design, it is possible that differences in these factors may have influenced the results. Differences in injury patterns may also affect cause of death (such as from hemorrhage or brain injury), but we did not have access to precise causes of death for each patient. The reduced mortality observed in both the current cohort of major trauma patients and two studies of orthopedic trauma populations is conflicting with a study of the general trauma population, but it is unknown what may have caused these differences.17 18 20 Additionally, although hospital and ICU admissions have varied over time (figure 2), we did not have access to any changes in precise indications for admission to ICU during the study period. Multicentered prospective studies with greater granularity of data may be warranted to better delineate the relationship between outcomes and different levels of severity of depression and different treatment modalities. We were also unable to measure outcomes once patients left the hospital and therefore could not assess longer-term outcomes.