Association of depression symptom severity with short-term risk of an initial hospital encounter in adults with major depressive disorder

Major depressive disorder (MDD) is a common and frequently recurrent psychiatric condition characterized by significant social and functional impairment [1, 2]. In 2018, 7.2% of adults in the United States reported they had experienced at least one major depressive episode in the prior year, with 65% reporting severe impairment [3]. In addition to an associated increased risk with poor health outcomes, including early onset and increased severity of chronic comorbid diseases and hospitalization [4‐6], MDD is associated with an increased risk of suicidal ideation and suicide attempt [7, 8], as well as all-cause mortality [6].

The American Psychiatric Association has established 9 symptom criteria for diagnosis of MDD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [9]; the number, frequency, and intensity of symptoms can range from none/minimal to severe [9, 10]. Clinicians may use validated instruments as screening tools to assist in making the diagnosis of MDD, to quantify symptom severity, and to monitor ongoing symptom severity. In 2016, the US Preventive Services Task Force (USPSTF) recommended routine screening for depression among adults in the US and suggested the 9-item Patient Health Questionnaire (PHQ-9) for this purpose [11].

The most recent data available, which was collected prior to 2016 USPSTF routine depression screening recommendations, shows that screening for depression in the primary care setting in the US has in the past been widely underused [12, 13]. Based on National Ambulatory Care Surveys (NACS), Samples et al. reported only a 3.0% rate during years 2005 to 2015 of depression screening among visits to outpatient physician offices in the US [12]; the rate was reported at 4.2% in another study of physician-patient encounters based on 2012–2013 NACS data [13]. Patients with acute worsening of depression symptoms may present to the emergency room (ER), and the underuse of outpatient depression screening may contribute to this presentation. A study based on data from the Nationwide Emergency Department Sample reported that in 2014, ER visits for depression had increased by nearly 26% since 2006 in the US; over half of such ER visits in 2014 led to an inpatient stay that lasted on average 5.6 days [5]. In years 2014–2015 in the US, the average inpatient stay for MDD was 6 days with an average cost of $6713 [14]. The growing burden of mental illness on the healthcare system in the US is detailed in the 2017 report of the National Council for Behavioral Health Medical Director Institute, which notes that across all care settings (inpatient, outpatient, community, workforce, etc) there is insufficient access for those who are mentally ill [15]. In particular, there is an extensive and widespread psychiatric inpatient bed shortage, which contributes to exorbitantly long wait times in the ER for psychiatric care (up to 23 h on average for some dispositions) [15].

A better understanding of the impact of depression symptom severity on future use of healthcare resources, specifically that provided by hospitals, may be helpful to better determine the most appropriate targeted interventions that can be implemented earlier in the course of worsening depression symptoms. A few small-scale studies conducted in the US have found depression severity to impact use of healthcare resources, including hospital encounters and mental health services [16, 17]. Adekkanattu et al. recently developed a natural language processing (NLP) method to extract PHQ-9 scores from unstructured data in electronic health records (EHRs) that exhibited high accuracy (97%) and sensitivity (98%) compared to a reference standard to identify patients with MDD and had utility for stratifying patients by depression severity [18]. Utilizing a similar NLP approach to extract PHQ-9 assessment data developed by Optum (Eden Prairie, MN), in this study we evaluated whether depression symptom severity, as measured by PHQ-9 score, in a large US population of patients diagnosed with MDD is associated with short-term risk of a hospital encounter.

This is the first large-scale study in the US to evaluate the association between depression symptom severity and short-term risk of hospital encounters of patients with MDD. Among more than 280,000 US adult patients diagnosed with MDD who had a PHQ-9 assessment in an outpatient care setting, 26.9% were categorized as having none/minimal depression symptom severity, 16.4% as mild, 24.7% as moderate, 19.6% as moderately severe, and 12.5% as severe. A notable finding of this study was the nearly stepwise manner that depression symptom severity was associated with an increased risk of an MDD-related hospital encounter in the short-term following a PHQ-9 assessment; the increased risk ranged from 27 to 164% among those with mild to severe depression symptom severity compared to those with none/minimal. These study findings were obtained after adjustment for differences in patient demographics and clinical characteristics, including presence of comorbid psychiatric disorders and receipt of depression treatment, indicating that depression symptom severity is a key driver of the short-term risk of presentation to the hospital setting. Moreover, our study findings imply that taking steps towards improving depression symptoms, even if by only one severity category, may be helpful to incrementally reduce the risk of short-term HRU, particularly among those in the highest severity categories.

The findings of this study significantly contribute to the accumulating evidence of the association of depression symptom severity with increased HRU in the US observed in a few other studies conducted on a considerably smaller scale of patients with MDD [16, 17]. Beiser et al. conducted a prospective cohort study of 999 adults who presented to the ER for care other than for a psychiatric illness at a single US academic medical center in 2015 [16]. Based on depression diagnostic screening and depression severity measurement administered via a tablet computer during the ER visit, patients identified with MDD (27%) had a significantly greater risk of a subsequent ER visit (61% increased risk) and hospitalization (49% increased risk) during the 1 year follow-up period than those without MDD; furthermore, each 10% increase in MDD severity was associated with a 10% greater relative risk of a subsequent hospital encounter [16]. In another study of 539 individuals who self-rated their MDD using the Quick Inventory of Depressive Symptomatology Self-Report (2001–2002), 13.8% were classified as having mild depression, 38.5% as moderate, and 47.7% as severe; those with moderate and severe MDD used mental health services to a greater extent than those with mild disease, as well as had greater prevalence of unemployment, reduced work productivity, and disability [17]. A relatively larger study of 10,443 individuals in Stockholm, Sweden (1998–2014) reported that those with subsyndromal, mild, moderate, and severe depression, according to scores on the Major Depression Inventory, had higher incidence rates of mental health-related hospitalizations and outpatient care visits than non-depressed individuals; similar to our study, Sun et al. reported that as depression severity level increased, so did the rate of HRU [26].

Another remarkable finding of this study pertains to the association of increased depression symptom severity with increased risk of all-cause hospital encounters. Compared to patients with MDD and none to minimal depression symptom severity, according to index PHQ-9 assessments, those with mild symptoms had a 7% increased risk of an all-cause hospital encounter in the short-term following their PHQ-9 assessment, those with moderate had an 18% increased risk, those with moderately severe had a 36% increased risk, and those with severe had a 60% increased risk. This stepwise association of depression symptom severity level with increased relative risk of an all-cause hospital encounter in the short-term following a PHQ-9 assessment was observed after adjustment for age and the presence of Elixhauser comorbidities. Reviewed in Kessler et al. [6], a number of other studies have previously shown that MDD is associated with early onset and/or increased severity of several comorbid chronic illnesses, including cardiovascular disease, diabetes, respiratory illnesses, and chronic pain. Reported in a systematic review of several studies, depressive symptoms are a significant predictor of general hospital admissions for non-psychiatric reasons (RR: 1.36, 95% CI: 1.28–1.44), as well as longer inpatient lengths of stay and higher readmission risk [27]. The findings of our study add to this existing evidence of the association of MDD with increased HRU for non-psychiatric reasons by demonstrating the impact of increased depression symptom severity on the increased likelihood of all-cause HRU in the short-term. The reasons surrounding the association of depression symptom severity with greater utilization of healthcare resources in general are not well understood, but could be related to suboptimal treatment options, inadequate adherence to medications or treatments, a greater prevalence of chronic conditions (eg, substance abuse disorders, smoking history), lack of follow-up care by patients and/or providers, sociodemographic disparities, access to psychiatric care facilities, etc.

Two other studies conducted in the last decade in the US have also examined the distribution of patients with MDD across symptom severity categories based on PHQ-9 assessments, although they did not explore HRU to a significant extent [28, 29]. In a study of 1019 patients diagnosed with MDD (2006–2010 population sample from 9 US states in different geographic regions), Valuck found a generally similar distribution of patients with MDD across PHQ-9 score categories [28]. In another population of patients with MDD in the US (N = 315, 2014–2016), Bushnell et al. reported 6.7% of patients with none/minimal (PHQ-9 score: 0–4), 26.7% with mild (PHQ-9 score: 5–9), 21.9% with moderate (PHQ-9 score: 10–14), 27.6% with moderately severe (PHQ-9 score: 15–19), and 17.1% with severe (PHQ-9 score: 20–27) depression [29]. In our study, PHQ-9 scores of patients diagnosed with MDD were documented in EHRs, and therefore likely do not fully represent the distribution of severity categories among the overall population of patients with MDD in the US, especially those who have not been diagnosed and/or are without access to routine healthcare. Furthermore, a large proportion of patients represented in this study were from the Midwest region of the US; this particular region also contributed disproportionately to the none/mild depression symptom severity category. These findings may suggest that the PHQ-9 is used more routinely and that there is greater access to depression treatment in the Midwest compared to other US regions. Additionally, African American patients with MDD disproportionately were in the highest depression symptom severity categories. Several factors could contribute to this finding, including reduced access to routine healthcare resources where lower severity MDD may be assessed and documented. Nevertheless, the distribution of MDD patients across the PHQ-9 categories observed in this analysis broadly matches that observed in other studies with much smaller populations [28, 29].

This study has strengths in that it included a very large population of patients diagnosed with MDD across the US who had a PHQ-9 assessment, a validated instrument for measuring depression symptom severity [19]. Since the PHQ-9 has been shown to have good agreement with clinician depression rating scales (eg, Hamilton Depression Rating Scale) commonly used in clinical trial settings [30], the population-level data herein may be useful to apply to clinical trial data for economic modeling and other treatment-related measurement purposes. Furthermore, Optum’s NLP technology allowed for the timely extraction of large amount of PHQ-9 score data from complex clinical notes available in the EHRs. In addition, the marginal structural model (MSM) allowed us to identify the adjusted absolute risk at each level of severity level, which is not possible with conventional regression techniques. MSM is also agnostic about the effect modification by any covariates, therefore the relative risk estimates are not subject to model misspecification with respect to any product terms between depression severity and baseline covariates that could be possibly mis-specified in conventional regression techniques.

This study of over 280,000 adults with MDD in the US is the largest study to date to evaluate how depression symptom severity, according to PHQ-9 assessments during an outpatient appointment, impacts the likelihood of presenting to a hospital in the short-term. The study findings highlight the nearly stepwise manner that depression symptom severity is associated with increased risk of initial all-cause and MDD-related hospital encounters in the 30 days following an outpatient PHQ-9 assessment. Additionally, they emphasize the importance of routine depression screening and timely intervention with efficacious treatments, including pharmacotherapy, psychotherapy, and other types of individualized patient management strategies potentially implemented in the outpatient setting, as prevention tactics to mitigate the course of acute worsening of symptoms of MDD and reduce some of the burden currently incurred by hospital systems.