The cost-of-illness and burden-of-disease of treatment-resistant depression in Austria

Figures & data

Figure 1. Cost-of-Illness and burden- of- disease analysis overview.

Figure 2. Patient-flow.

Table 1. Input data direct costs.

Parameter	Methodology and sources
Treatment costs
AUG-LI (Augmentation therapy with oral antidepressants and lithium)	The annual cost for lithium treatment and the annual cost for SSRI/SNRI treatment are combined, using the reimbursement prices of the most affordable preparations. The daily dose of lithium is derived from the results of the expert survey. Sources: Expert survey, Austrian Pharmaceutical Index 07/21^29
AUG-AP (Augmentation therapy with oral antidepressants and antipsychotics	The weighted annual costs for antipsychotics treatment and the annual costs for SSRI/SNRI treatment are added up. The TRD patient shares and daily dose per active ingredient are sourced from the results of the expert survey and the publication of Konstantinidis et al. (2012). Sources: Expert survey, Konstantinidis et al. (2012)^30. Austrian Pharmaceutical Index 07/21^29
CT (Combination therapy with antidepressants of different pharmacological classes)	Weighted annual cost for a treatment with mirtazapine or trazodone and SSRI/SNRI antidepressants are calculated. The TRD patient shares and daily dose per active ingredient are estimated from IQVIA market data and the results of the expert survey. Sources: Expert survey, IQVIA 2019^31, Austrian Pharmaceutical Index 07/21^29
DE (Dose escalation of the current antidepressant)	According to the results of the expert survey, SSRI/SNRI antidepressants are most often used with this treatment regimen. The weighted annual cost of SSRI/SNRI treatment at the recommended maximum daily doses (Kasper et al. 2021) is calculated. Sources: Expert survey, Kasper et al. 2021^32, Austrian Pharmaceutical Index 07/21^29
SW (Switch of treatment to an antidepressant of a different pharmacologicalal class)	A percentage redistribution of TRD patients between the SSRI, SNRI, NaSSA, MAOI, and tricyclic drug classes is assumed. The percentage redistribution is based on the principle that all patients in one drug class before the switch are redistributed to all other considered drug classes after the switch. The redistribution from one drug class is done according to the patient share of each other drug class scaled to 100%. The annual therapy costs with SSRI, SNRI, NaSSA, MAOI, and tricyclic antidepressants are calculated as the annual therapy costs of the respective lead compound per drug class in 2019. The daily doses of the lead compounds are determined from the results of the expert survey and the WHO ATC/DDD Index 2019. Sources: Expert survey, WHO 2019^33, Austrian Pharmaceutical Index 07/21^29
Non-pharmacological treatments	It was not possible to collect representative quantity structures for these treatments and to determine the corresponding costs. It can be assumed that the implementation of non-pharmacological therapies are mainly carried out on an inpatient basis and are reimbursed via DRG positions. Source: Expert survey, own assumptions
Weighted treatment costs	These annual costs of the individual regimens are weighted by the estimated proportion of TRD patients in Austria for three consecutive lines of therapy, derived from the results of the expert survey. Sources: Expert survey
Outpatient costs	Annual outpatient costs are calculated from the -quantity structures derived from the expert survey for the health states “PHQ-9 15-27: moderately severe to severe symptoms – acute depressive episode” and “PHQ-9 5-14: mild to moderate symptoms – response” and Austrian cost data. These costs are weighted with35.60% and 64.40% respectively, to obtain the cost of an average TRD patient, according to the publication by Sousa et al. (2022)^34. Sources: Expert survey, Supraregional evaluation of the documentation of hospitals financed by the state health funds 2019^35, Austrian DRG model 2021^36, Fee schedules of the Austrian Health Insurance Fund^37, Sousa et al. (2022)^34
Inpatient costs	Inpatient costs were calculated using the same approach as outpatient costs. Sources: Expert survey, Austrian DRG model 2021^36, Sousa et al. (2022)^34
Costs for TRD-related diagnostic measures	Costs for TRD-related diagnostic measures were calculated using the same approach as for outpatient costs. Cost items from the inpatient fee schedules were used to calculate costs for TRD-related diagnostic measures of the health state "PHQ-9 15-27: moderately severe to severe symptoms – acute depressive episode" and positions from the outpatient fee schedules were used to calculate costs for the health state "PHQ-9 5-14: mild to moderate symptoms – response". Sources: Expert survey, Supraregional evaluation of the documentation of hospitals financed by the state health funds 2019^35, Private payer fee schedule Vienna 2021^38, Fee schedules of the Austrian Health Insurance Fund^37, Sousa et al. (2022)^34

Table 2. Input data indirect costs.

	Women	Men	Average	Source
Gross Income per year
Age 18–29	14,926	22,189	17,272	Statistik Austria^40
Age 30–39	20,808	36,582	25,903
Age 40–49	25,428	40,561	30,316
Age 50–59	28,661	44,079	33,641
Age 60+	44,349	49,236	45,928
Employed			39.2%	Jaffe et al. 2019^4
Employment rate general population
Age 18–29			76.72%	Statistik Austria^41
Age 30–39			88.38%
Age 40–49			90.33%
Age 50–59			84.85%
Age 60+			13.48%
Absenteeism in %			35.9%	Jaffe et al. 2019^4
Presenteeism in %			45.6%	Jaffe et al. 2019^4

Table 3. Input data intangible costs.

	Value	Source
Disability weight
Mild depression	0.145	Salomon et al. 2015^44
Moderate depression	0.396
Severe depression	0.658
Severity distribution
Mild depression	4.60%	Sousa et al. 2021^34
Moderate depression	31.0%
Severe depression	64.40%
Suicide rates
Acute depressive disorder	0.47%	Bergfeld et al. 2018^28
Response	0.23%	Assumption

Table 4. Base-case cost-of-illness results.

Cost components	Per patient	TRD Cohort (n = 43,732)
Direct cost	7,890.08 €	345,047,195.55 €
Drug costs	247.07 €	10,804,617.19 €
Outpatient costs	1,508.77 €	65,981,070.35 €
Inpatient costs – psychiatry normal ward	4,868.34 €	212,901,387.77 €
Inpatient costs – ICU	384.35 €	16,808,128.00 €
TRD-related diagnostics	881.56 €	38,551,992.24 €
Indirect costs	15,657.06 €	684,711,382.97 €
Absenteeism	4,482.41 €	196,023,905.54 €
Presenteeism	5,690.70 €	248,864,657.57 €
Reduced employment rate	3,582.01 €	156,647,577.53 €
Premature death	1,901.94 €	83,175,242.33 €
Total costs	23,547.14 €	1,029,758,578.52 €

TRD = Treatment-resistant depression, ICU = Intensive care unit.

Table 5. Base-case cost-of-illness subgroup results.

Cost components	PHQ-9: 5–14	PHQ-9: 15–27	18–29	30–39	40–49	50–59	60+	Women	Men
Direct cost	2,462.44 €	10,890.45 €	7,890.08 €	7,890.08 €	7,890.08 €	7,890.08 €	7,890.08 €	7,890.08 €	7,890.08 €
Drug costs	247.07 €	247.07 €	247.07 €	247.07 €	247.07 €	247.07 €	247.07 €	247.07 €	247.07 €
Outpatient costs	639.71 €	1,989.18 €	1,508.77 €	1,508.77 €	1,508.77 €	1,508.77 €	1,508.77 €	1,508.77 €	1,508.77 €
Inpatient costs – psychiatry normal ward	1,313.99 €	6,833.18 €	4,868.34 €	4,868.34 €	4,868.34 €	4,868.34 €	4,868.34 €	4,868.34 €	4,868.34 €
Inpatient costs – ICU	25.05 €	582.97 €	384.35 €	384.35 €	384.35 €	384.35 €	384.35 €	384.35 €	384.35 €
TRD-related diagnostics	236.63 €	1,238.07 €	881.56 €	881.56 €	881.56 €	881.56 €	881.56 €	881.56 €	881.56 €
Indirect costs	11,335.63 €	19,193.45 €	10,399.64 €	13,918.71 €	15,451.15 €	16,148.85 €	20,869.24 €	13,688.26 €	19,783.62 €
Absenteeism	3,302.83 €	5,448.55 €	2,431.34 €	3,646.29 €	4,267.49 €	4,735.55 €	6,465.09 €	3,918.77 €	5,663.79 €
Presenteeism	4,090.71 €	6,999.61 €	3,086.74 €	4,629.20 €	5,417.85 €	6,012.08 €	8,207.83 €	4,975.13 €	7,190.54 €
Reduced employment rate	1,367.19 €	2,339.40 €	1,942.95 €	2,913.84 €	3,410.26 €	3,784.30 €	5,166.41 €	3,131.59 €	4,526.08 €
Premature death	2,574.89 €	4,405.90 €	2,938.61 €	2,729.38 €	2,355.54 €	1,616.92 €	1,029.91 €	1,662.78 €	2,403.21 €
Total costs	13,798.06 €	30,083.90 €	18,289.72 €	21,808.79 €	23,341.22 €	24,038.93 €	28,759.31 €	21,578.34 €	27,673.70 €

TRD = Treatment-resistant depression, ICU = Intensive care unit, PHQ-9 = Patient Health Questionnaire 9.

Figure 3. Deterministic sensitivity analysis visualized as Tornado plots where each bar represents a one-way sensitivity analysis (OWSA), and the width of bars represents the impact on total cost-of-illness or DALYs lost. The total cost-of-illness or DALYs are plotted on the x-axis. (a) OWSA for cost-of-illness. (b) OWSA for DALYs.

Table 6. Disability adjusted life years.

DALYs	TRD cohort
Years of Life Lost due to Disability – YLD	24,192
Years of Life Lost due to premature death – YLL	5,692
Total DALYs	29,884

DALYs = Disability-adjusted life years, TRD = Treatment-resistant depression.

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