This multisite, prospective longitudinal study of 186 ALI survivors demonstrates that incident depressive symptoms and incident impaired physical function are common and long-lasting during the first 2 years after ALI. Our analyses indicate that depressive symptoms are not only relatively persistent in ALI survivors but also an independent risk factor for subsequent impairment in physical function. Hence, early identification and treatment of depressive states should be evaluated as a potential intervention to minimize the suffering and impairment that affect so many of these patients.
The cumulative 2-year incidences of depressive symptoms and impaired physical function after ALI were high at 40 and 66%, respectively. Incidence was highest by 3-month follow-up, as might be expected after a severe critical illness. However, the presence of additional incident cases throughout the 2-year follow-up period suggests that events after the ALI hospitalization (e.g., further illness and hospitalization, and financial and other stressors [38
]) contribute to ongoing morbidity for ALI survivors. Importantly, most survivors with post-ALI incidence of depressive symptoms or impaired physical functioning were affected at the last follow-up. The most common pattern was to have incidence by 3-month follow-up and persistence through the last follow-up. Given that depressive symptoms and impaired physical function are common and persistent/recurrent in ALI survivors, comprehensive and ongoing evaluation, treatment, and rehabilitation of these patients are necessary (40
The point prevalences of substantial depressive symptoms in the current report (24–32% during the first 2 yr post-ALI) are comparable to those in previous studies of ALI survivors (range 17–43%, median 28% during the first 2 yr post-ALI) (1
). These point prevalences are substantially higher than the 8% point prevalence of an HAD depression score greater than or equal to 8 in a large nonclinical sample of adults (17
We identified several risk factors for incident depressive symptoms in ALI survivors: lower education, baseline disability or unemployment, baseline comorbid medical conditions, and lower blood glucose in the ICU. We previously reported that lower in-ICU blood glucose appeared particularly relevant to depressive symptoms early in the follow-up period (i.e., at 3-mo follow-up) (30
). Having 12 or fewer years of education was a particularly strong and independent risk factor for incident depressive symptoms in this study. Lower education and other indicators of low socioeconomic status are well-established risk factors for depressive illness (41
We also identified two risk factors for incident physical impairment in ALI survivors: longer ICU length of stay and prior depressive symptoms. Having prior depressive symptoms was a particularly strong and independent risk factor for incident physical impairment in this study. Importantly, although a history of depression is often noted in patients admitted to an ICU, antidepressants are often stopped in this setting; starting or restarting antidepressants and/or psychotherapy early during patient recovery might improve long-term physical and psychiatric outcomes in ALI survivors (42
Several possible mechanisms may explain why depressive symptoms are a risk factor for impaired physical function in ALI survivors. First, depressive symptoms may decrease motivation for, and reward from, physical activities necessary for recovery or maintenance of functioning (43
). This is consistent with our clinical experience that depressed patients are more difficult to engage in physical therapy, which is often crucial for recovery of function (28
). Second, depressive symptoms can amplify symptoms of general medical illnesses (44
), and an increased physical symptom load could negatively affect functioning. Third, depressive symptoms can affect adherence to medication regimens (46
), which could worsen the course of general medical illnesses. Fourth, depressive symptoms could affect functioning through direct neurobiologic pathways, including neuroendocrine and inflammatory mechanisms (47
). Finally, it is possible that depressive symptoms negatively influence patients’ perceptions of what they are able to do; nevertheless, like others (48
), we do not doubt that depression-associated impairments in functioning are real, based on our clinical experience with these patients.
There are several potential limitations of this study. First, we measured depressive symptoms using a well-validated self-report questionnaire (15
), rather than psychiatric diagnoses using expert clinicians with specialized training to perform semistructured interviews and incorporate informant and medical record data (49
). We believe that, given the added burden for participants, the latter method would have pushed the limits of feasibility and resulted in substantially higher losses to follow-up and incomplete data, especially during the first 12 months when patients were still in early recovery and required three follow-up assessments. Obtaining psychiatric diagnoses also would have been logistically difficult, given the need for expert clinicians to be physically present in patients’ homes or long-term care facilities (58% of participants required at least one such visit during 2-yr follow-up).
Second, we used medical records to identify baseline (pre-ALI) depression, likely a relatively specific, but insensitive, method that could lead to an overestimate of the incidence of post-ALI depressive symptoms due to nondetection of baseline depression. On the other hand, chart review may have detected depression that had remitted well before ALI, thus potentially underestimating the incidence of post-ALI depressive symptoms. Such potential biases are generally unavoidable, given the infeasibility of directly assessing patients’ mood status immediately before ALI onset. To examine the validity of our method, we compared retrospectively ascertained pre-ALI SF-36v2 Mental Health domain scores in patients with and without baseline depression identified via their medical records. Pre-ALI Mental Health domain scores were substantially lower in patients with baseline depression (mean = 52, SD = 23) than in patients without baseline depression (mean = 72, SD = 23) (P < 0.001).
Third, we did not account for possible effects of treatment of depression or impaired physical function. Thus, we may have missed instances of depressive symptoms or impaired physical function that occurred and resolved before the first follow-up or in between follow-ups.
Fourth, although we statistically controlled for several potential confounders in our analyses of risk factors, residual confounding could have influenced the associations detected in this study. However, because it is not possible to randomize patients to depressive symptoms, physical impairment, or indeed many of the potential risk factors we examined, observational studies provide essential information regarding likely relationships. Given the findings of the current study, it is important to evaluate interventions for early identification and treatment of depressive states as part of a comprehensive post-ICU rehabilitation program (40
), to determine if such an intervention would improve patients’ mood states and physical functioning, as demonstrated previously in populations of elderly depressed persons (48
Incident depressive symptoms and incident impaired physical function are common and long-lasting during the first 2 years after ALI. Depressive symptoms are an independent risk factor for impaired physical function in this population. Hence, early identification and treatment of depressive states should be evaluated as a potential intervention to improve ALI survivors’ long-term outcomes.