Participant Demographic and Health Characteristics

Out of 74,994 survey respondents, a total of 10,710 participants had a self-reported diagnosis of MDD and were compared with 52,687 participants who did not self-report a diagnosis of MDD or bipolar disorder. Of the participants with MDD, 5905 (55%) were classified in the minimal/mild cohort, 2206 (21%) in the moderate cohort, 1565 (15%) in the moderately severe cohort, and 1034 (10%) in the severe cohort. Participants with MDD had a mean (SD) duration of MDD of 13.8 (10.9) years.

Demographic and health characteristics of participants with versus without MDD are shown in Table 1. On average, the cohort of participants with MDD was younger than the cohort without MDD (44.4 vs 49.4 years, P < 0.05) and included more female participants (70.6% vs 53.1%, P < 0.05). Additionally, MDD was consistently associated with poorer socioeconomic status. For example, a significantly higher proportion of participants with MDD relative to those without MDD were single, unemployed, had less than a university education, reported long- or short-term disability, and had an annual household income of less than $25,000 per year (each comparison, P < 0.05). MDD was also associated with poorer general health. Relative to participants without MDD, those with MDD reported a greater comorbidity burden as measured by the CCI, a greater level of anxiety as measured by the GAD-7, a greater number of mental health diagnoses, and greater average BMI; they were also more likely to currently smoke and less likely to exercise (each comparison, P < 0.05).

Table 1 Demographic and health characteristics in participants with MDD versus without MDD

Furthermore, socioeconomic status and general health decreased with increasing MDD severity (Supplementary Table 1). For instance, relative to participants with minimal/mild MDD, those with severe MDD were more likely to be unemployed (43.0% vs 52.6%), have an annual household income of less than $25,000 per year (19.5% vs 33.9%), report short- or long-term disability (6.3% vs 15.8%), have less than a university education (40.5% vs 58.5%), and be uninsured (8.0% vs 15.4%; each comparison, P < 0.05). Additionally, compared with the minimal/mild MDD cohort, participants with severe MDD reported a higher BMI (29.6 vs 30.8, P < 0.05), a higher number of comorbid mental health diagnoses (1.3 vs 2.3, P < 0.05), a higher comorbidity burden as measured by the CCI (0.61 vs 0.79, P < 0.05), and a greater level of anxiety as measured by the GAD-7 (4.6 vs 15.1, P < 0.05). They were also more likely to currently smoke (16.7% vs 26.3%, P < 0.05) and less likely to exercise (36.6% vs 48.3%, P < 0.05).

Analysis of MDD treatment revealed approximately 60% of participants with MDD were currently using a prescribed medication for treatment. Of these participants, over 80% were on a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI). The second most common prescription was for bupropion (21%), followed by atypical antipsychotics/antipsychotic combination pills (8%). Of those not currently on medication for MDD, 63% had previously been prescribed a treatment. In the overall MDD cohort, the mean (SD) medication adherence was 87.3% (22.9) as measured on a 0–100 VAS. Participants in the minimal/mild MDD cohort had a longer duration of medication use than participants with severe MDD (81.8 months vs 59.6 months, P < 0.05) and higher medication adherence as measured on a 0−100 VAS (90.0% vs 82.1%, P < 0.05); current use of a prescription medication and type of medication used generally did not significantly differ across MDD severity levels.

Impact of MDD on Health-Related Quality of Life, Health Care Resource Utilization, and Cost OutcomesHealth-Related Quality of Life

Relative to participants without MDD, participants with MDD reported significantly lower HRQoL, with lower scores on both the mental and physical components of the SF-36v2 and EQ-5D VAS (Fig. 1a). Additionally, MDD severity was strongly associated with HRQoL—as depression severity increased, HRQoL decreased as shown by significantly lower scores in SF-36v2 (both mental and physical components) and EQ-5D VAS scores across the moderate, moderately severe, and severe MDD cohorts versus the minimal/mild MDD cohort (Fig. 1b).

Fig. 1

HRQoL of a participants with MDD versus without MDD and b across MDD severity levels. ***P < 0.001 vs participants without MDD; †††P < 0.001 vs the minimal/mild MDD cohort; higher scores indicate better HRQoL. aEstimates shown were derived from separate models predicting SF-36v2 MCS, SF-36v2 PCS, and EQ-5D VAS scores. Model covariates for comparing to the general population a included sex, age, race and ethnicity, education, employment status, income, insurance status, marital status, smoking history, CCI, and BMI, while severity comparisons b included additional covariates relating to early-onset MDD diagnosis status, number of comorbid mental health conditions, and current medication use for MDD. bSE values are labeled in the figure rather than shown as error bars given the small scale. BMI body mass index, CCI Charlson Comorbidity Index, EQ-5D VAS EuroQol Five-Dimension Visual Analogue Scale, HRQoL health-related quality of life, MCS mental component summary, MDD major depressive disorder, Mod Severe moderately severe, PCS physical component summary, SE standard error, SF-36v2 Short Form 36v2 Health Survey

Health utility scores followed a similar pattern to the SF-36v2 and EQ-5D VAS. The average SF-6D health state utility score for participants with MDD was significantly lower than those without MDD (0.64 vs 0.75, P < 0.001), and the average EQ-5D-5L utility score was significantly lower for participants with MDD (0.74) relative to patients without MDD (0.86; P < 0.001). Furthermore, utility scores decreased with increasing MDD disease severity. The SF-6D health state utility scores decreased across minimal/mild (0.66), moderate (0.59), moderately severe (0.56), and severe MDD (0.52; each comparison vs mild MDD cohort, P < 0.001). Additionally, the average EQ-5D-5L utility scores were 0.77, 0.71, 0.65, and 0.57 for patients with minimal/mild, moderate, moderately severe, and severe MDD, respectively (each comparison vs minimal/mild MDD cohort, P < 0.001).

Health Care Resource Utilization

Relative to participants without MDD, participants with MDD reported a significantly greater number of HCP visits and ED visits during the 6 months prior to survey completion; the number of hospitalizations was similar (Fig. 2a). Increasing MDD severity was also associated with greater HCRU. Compared with the minimal/mild MDD cohort, participants with moderate, moderately severe, or severe MDD had a greater average number of HCP visits (minimal/mild = 5.47, moderate = 6.05, moderately severe = 6.51, severe = 6.91), ED visits (minimal/mild = 0.26, moderate = 0.33, moderately severe = 0.37, severe = 0.46), and hospitalizations (minimal/mild = 0.01, moderate = 0.17, moderately severe = 0.18, severe = 0.22) in the past 6 months. All HCRU differences between the minimal/mild cohort and the moderate, moderately severe, and severe cohorts were significant (each comparison, P < 0.05; Fig. 2b).

Fig. 2

HCRU of a participants with MDD versus without MDD and b across MDD severity levels. ***P < 0.001 vs participants without MDD; †P < 0.05, ††P < 0.01, †††P < 0.001 vs the minimal/mild MDD cohort. aEstimates shown were derived from separate models predicting the number of HCP visits, ED visits, and hospitalizations. Model covariates for comparing to the general population a included sex, age, race and ethnicity, education, employment status, income, insurance status, marital status, smoking history, CCI, and BMI, while severity comparisons b included additional covariates relating to early-onset MDD diagnosis status, number of comorbid mental health conditions, and current medication use for MDD. bSE values are labeled in the figure rather than shown as error bars given the small scale. BMI body mass index, CCI Charlson Comorbidity Index, ED emergency department, HCP health care provider, HCRU health care resource utilization, MDD major depressive disorder, Mod Severe moderately severe, SE standard error

Average Direct Medical Costs

Annualized mean total direct medical costs were significantly higher for participants with MDD ($8814) than for participants without MDD ($6072; P < 0.001; Fig. 3a). Participants with versus without MDD also had significantly higher annualized mean direct medical costs for HCP visits ($3571 vs $1662; P < 0.001), ED visits ($559 vs $366; P < 0.001), and hospitalizations ($4408 vs $3495; P < 0.01). Furthermore, increasing severity of MDD was associated with incrementally higher annualized mean total direct medical costs, with significant differences versus the minimal/mild MDD cohort for all severity levels (each comparison, P < 0.05; Fig. 3b). The average costs of HCP and ED visits increased with increasing MDD severity (HCP costs: minimal/mild = $3414; moderate = $3811; moderately severe = $4083; severe = $4352; each comparison vs minimal/mild MDD cohort, P < 0.01; ED costs: minimal/mild = $553; moderate = $711; moderately severe = $775; severe = $1063; each comparison vs minimal/mild MDD cohort, P < 0.01). While the average cost attributable to hospitalizations was numerically higher in the more severe groups, the differences were not statistically significant (minimal/mild = $3927; moderate = $5121; moderately severe = $5187; severe = $6398, each comparison vs minimal/mild MDD cohort, P > 0.05).

Fig. 3

Annualized direct medical costs of a participants with MDD versus without MDD and b across MDD severity levels. **P < 0.01, ***P < 0.001 vs participants without MDD; †P < 0.05, ††P < 0.01, †††P < 0.001 vs the minimal/mild MDD cohort. aEstimates shown were derived from separate models predicting the cost of HCP visits, ED visits, hospitalizations, and total costs; therefore, individual component costs may not add up to total costs. Further, model covariates for comparing to the general population a included sex, age, race and ethnicity, education, employment status, income, insurance status, marital status, smoking history, CCI, and BMI, while severity comparisons b included additional covariates relating to early-onset MDD diagnosis status, number of comorbid mental health conditions, and current medication use for MDD. BMI body mass index, CCI Charlson Comorbidity Index, ED emergency department, HCP health care provider, MDD major depressive disorder, Mod Severe moderately severe

Average Indirect Costs

Participants with MDD incurred significantly greater annualized mean total indirect costs versus participants without MDD ($5425 vs $3085; P < 0.001; Fig. 4a). The average costs of absenteeism and presenteeism were also significantly higher for participants with versus without MDD. Compared with participants in the minimal/mild MDD cohort, participants in the moderate, moderately severe, and severe MDD cohorts had significantly greater annualized mean total indirect costs (minimal/mild = $4490; moderate = $6537; moderately severe = $7438; severe = $8797; each comparison vs minimal/mild MDD cohort, P < 0.001; Fig. 4b). Increasing MDD severity was also associated with higher average costs of absenteeism (minimal/mild = $1201; moderate = $1802; moderately severe = $2138; severe = $3233) and presenteeism (minimal/mild = $3225; moderate = $4662; moderately severe = $5222; severe = $5461) relative to those of the minimal/mild MDD cohort (each comparison vs minimal/mild MDD cohort, P < 0.001).

Fig. 4

Annualized indirect costs of a participants with MDD versus without MDD and b across MDD severity levels. ***P < 0.001 vs participants without MDD; †††P < 0.001vs the minimal/mild MDD cohort. aEstimates shown were derived from separate models predicting the cost of absenteeism, the cost of presenteeism, and total costs; therefore, individual component costs may not add up to total costs. Further, model covariates for comparing to the general population a included sex, age, race and ethnicity, education, employment status, income, insurance status, marital status, smoking history, CCI, and BMI, while severity comparisons b included additional covariates relating to early-onset MDD diagnosis status, number of comorbid mental health conditions, and current medication use for MDD. BMI body mass index, CCI Charlson Comorbidity Index, MDD major depressive disorder, Mod Severe moderately severe

Total Costs

Annualized mean total costs (direct medical plus indirect costs) were significantly higher for participants with MDD versus without MDD ($14,658 vs $9091; P < 0.001). Increasing MDD severity was also associated with increasing mean total costs, with significantly higher total mean costs in the moderate ($17,314), moderately severe ($18,263), and severe ($20,901) MDD cohorts than in the minimal/mild MDD cohort ($12,756; each comparison, P < 0.001).

Subgroup Analysis of Participants with Prior MDD Medication Treatment Failure

The prior MDD medication treatment failure subgroup analysis included 1077 participants with MDD who indicated that their current medication had replaced a prior medication because of non-response. Of these participants, severity cohorts were as follows: minimal/mild, n = 517 (48%); moderate, n = 244 (23%); moderately severe, n = 187 (17%); and severe, n = 129 (12%) (Table 2).

Table 2 Demographic and health characteristics in the prior MDD medication treatment failure subgroup across MDD severity levels

Table 3 summarizes the HRQoL, HCRU, and cost data across severity levels of participants with a prior MDD medication treatment failure. Observed trends were similar to those in the main analysis. Participants with severe MDD reported significantly more hospitalizations than those with minimal/mild MDD (0.22 vs 0.10, P < 0.05). Annualized mean total direct medical costs were significantly greater for participants in the severe prior MDD medication treatment failure cohort ($15,420) versus the minimal/mild prior MDD medication treatment failure cohort ($9852; P < 0.05). Furthermore, annualized mean total indirect costs were significantly greater for all severity levels relative to minimal/mild MDD. Costs associated with absenteeism were only significantly greater in the severe MDD cohort versus the minimal/mild MDD cohort, while costs associated with presenteeism were significantly greater among all MDD severity cohorts compared with those in the minimal/mild MDD cohort.

Table 3 HRQoL, HCRU, and cost outcomes in the prior MDD medication treatment failure subgroup across MDD severity levels