The one year cumulative rate of MDD in this study sample is 7.9 (53.1%/6.7%) times greater than would be expected in the general population.26
Previous high quality studies may have underestimated the rates of MDD during the first year after TBI by reporting rates in the 12% to 42.3% range.7, 27, 28
Our rate estimate may be higher because we conducted frequent assessments and were able to capture the cases with transient (one month) major depressive episodes. In addition, the sample was characterized by high rates of depression related risk factors such as alcohol dependence and other preinjury mental health diagnoses. Nevertheless, due to incomplete data at each assessment time point, the rate and depression duration estimates are likely conservative.
Our data indicate that 15.7% of the sample was depressed at the time of injury and that 26.8% had a preinjury history of depression but were not depressed when injured (). Of the total sample, 11.4% had a major depressive episode both at injury and after the injury, 18.4% experienced a recurrence of major depressive episode after the injury, and 23.3% experienced MDD for the first time after the injury. Preinjury depression and depression at the time of injury heralded higher post-TBI rates of MDD compared to those with no depression history.
Nevertheless, by 12 months 41% of those with no preinjury depression history also had an episode of MDD. High rates of preinjury depression in this and other samples7, 29
compared to the lifetime prevalence of MDD in the general population (16.2%)30
is consistent with the notion that depression is a risk factor for TBI.29
Our estimate of preinjury depression may be higher than other studies because we included prior antidepressant treatment, prior psychotherapy for depression and history of suicide attempt as indicators of depression history.
Several features of MDD after TBI are pertinent to future detection and treatment efforts. About half of the cases that became depressed were identified by 3 months. These data contradict the theory that poor awareness of impairment precludes depressive reactions during the first 6 months after injury31
and suggest a window of opportunity for early identification and treatment or prevention efforts. Nevertheless, TBI survivors remained at risk of MDD throughout the first year regardless of preinjury depression history. Risk of post-TBI MDD probably persists beyond one year since the curves (, eFigures 3–5
) do not seem to level off by 12 months. In 27% of cases MDD lasted only one month and may not have required treatment. Depression after TBI was complicated by a history of substance abuse disorders and PTSD as well as cooccurring anxiety, conditions that can limit the efficacy of antidepressants.32
Multivariate risk factors for MDD following TBI are similar to those for primary MDD in the general population.33
History of depression around the time of injury and history of depression prior to that time were the strongest predictors of post-TBI depression. These data disconfirm the notion that prior history of psychiatric disorder is either unrelated to28
or inversely related to MDD following TBI.4
The relationship of alcohol dependence to both TBI34, 35
and depression merits particular attention as a potentially modifiable risk factor. We did not find a relationship between injury characteristics and rate of MDD. Severity of TBI as a predictor of MDD has been controversial.13
Other biological markers such as the APOE-ε4 allele, neurotransmitter and neuroendocrine changes, genetic polymorphisms, as well as psychosocial risk factors, merit further study,35
Depression after TBI was associated with comorbid anxiety and poorer functional outcomes in multiple domains one year after injury. After controlling for all variables associated with depression after TBI, MDD remained a significant predictor of poorer self-reported health and lower quality of life. These results are correlational; therefore, causality cannot be inferred. Prior research has linked post-TBI depression with a host of poorer subjective and objective outcomes.5–7
Effective depression treatment may reduce disability36
and this hypothesis deserves further research.
Depression was under-treated in the study sample. Moreover, based on primary care research, we suspect that an even smaller proportion received guideline level depression treatment.37
The dearth of rigorous pharmacotherapy and psychotherapy trials likely contributes to the inadequate treatment of MDD after TBI. Only one negative but underpowered Class I antidepressant (sertraline) treatment trial has been published.38
A randomized placebo-controlled depression prevention trial found that 50 mg of sertraline daily for 3 months after TBI resulted in significantly lower depression severity in the treated group versus controls at the end of the trial but not beyond.39
Psychotherapy was especially underutilized in our sample, possibly due to poor access to counseling. A trial of proactive telephone counseling has demonstrated that treated subjects reported less depressive symptomatology one year after TBI compared to usual care controls.40
Additionally, survey research indicates that people with TBI favor counseling and physical exercise over other depression treatment modalities.41
In-person or telephone counseling was preferred over Internet delivered depression treatment.
Characteristics and comorbidities of TBI related depression may influence treatment efficacy.35
For example, executive dysfunction, which is common following TBI, predicts poor response to selective serotonin reuptake inhibitors in non-TBI samples.42
Cognitive impairments may affect the feasibility and efficacy of standard psychotherapeutic interventions. Integrated medical and psychosocial interventions, including substance abuse interventions, might be required to produce satisfactory outcomes.
Systematic integration of mental health services into standard care of patients with TBI may be needed to improve long-term outcomes after TBI. Within inpatient rehabilitation, integrated clinical pathways can be used to organize early identification, risk assessment, diagnosis and guideline-driven treatment of MDD.43
Systematic depression screening and stepped care treatment protocols should be integrated into routine outpatient care. For those without or beyond routine follow-up, novel case-finding programs, possibly via scheduled telephone contacts,44
Internet based screening45
or other technology-assisted methods46
may be useful. The manner in which substance abuse treatment has been integrated into trauma care47
and depression treatment integrated into primary care48
may provide models of how to incorporate depression treatment into TBI care.
Several study limitations should be highlighted. First, the presence or absence of MDD was based upon structured telephone interviews using the PHQ-9, not more traditional diagnostic interviews such as the SCID. Nevertheless, we have reported excellent inter-rater reliability and good diagnostic sensitivity and specificity when comparing the PHQ-9 to the SCID in people with TBI.20
Caution should be exercised comparing these results to studies that have used other diagnostic approaches.
Next, the study was conducted at a single Level I trauma center serving the Northwestern United States. The patient population was characterized by high rates of Medicaid recipients and somewhat limited ethnic/racial diversity. The results of this study may not be generalizable to other regions or populations with different socioeconomic or ethnic/racial characteristics.
The recruitment rate for this study was 52%. While this rate seems low, other widely referenced prevalence studies were based on convenience or referral samples or did not report recruitment rates and did not assess selection bias.13
Trauma patients, especially persons with TBI, are difficult to recruit and follow49
resulting in unrepresentative samples. Our study sample was comparable to the non-recruited group on most dimensions, though they were younger, more likely to have completed high school and less likely to be on Medicaid.
We found no differences in rate of MDD among those with complicated mild, moderate or severe TBI. However, caution is advised extrapolating these results to persons with uncomplicated mild TBI, which constitute the majority of those who sustain TBI.1
Although a significant number of such cases seek medical attention, adequate information about rates of complicated recoveries is lacking and deserves future research.
In conclusion, MDD after TBI is highly prevalent and associated with increased comorbidity and disability. Because MDD after TBI is an invisible disorder within an often invisible injury, aggressive efforts are needed to educate healthcare providers about the importance of MDD in this population, to promote integrated systems of detection and multidisciplinary care, and to conduct intervention studies aimed at overcoming multiple barriers to effective treatment.