The cost-effectiveness of zuranolone versus selective serotonin reuptake inhibitors for the treatment of postpartum depression in the United States

Figures & data

Figure 1. Model structure diagram.

Table 1. Model inputs.

Parameter	Base	Low	High	Distribution, SE if varied in probabilistic sensitivity analysis	Reference/Note
Starting patient age	30	19	44	Uniform	Sage DoF
Weeks since birth at BL	23	4	52	Uniform	Sage DoF
Discount rate (annual)	3%	0%	6%		^84
Share of mothers with a partner (utilities)	100%	51%	100%		Assumption
Share of mothers with a partner (costs)	63%	51%	100%		^72
Time horizon for partner outcomes (years)	11				Assumption
Treatment-related Inputs – Health Care Costs and Utilization
Zuranolone treatment arm
Cost of zuranolone (14-day treatment course)	$15,900
Cost of antidepressants (per week)	1.17	0.30	11.43	Gamma, 2.84	Avg. mg cost of sertraline (Redbook, accessed 4/19/2023) × Zoloft daily dose for MDD (50 mg)
Weeks of antidepressants	26	8	52	Uniform	Assumption based on clinical expert input
Percent of ZRN patients who receive antidepressants	22.45%	14.19%	30.71%	Beta, 0.0543	Sage DoF
SSRI treatment arm
Cost of antidepressants (per week)	$1.17	$0.30	$11.43	Varied as above	Avg. mg cost of sertraline (Redbook, accessed 4/19/2023) × Zoloft daily dose for MDD (50 mg)
Weeks of antidepressants	26	8	52	Varied as above	Assumption based on clinical expert opinion
Adverse Events
Withdrawal (w/d) symptoms from discontinuing SSRIs
Share of antidepressant patients experiencing w/d symptoms	56%	27%	86%	Beta, 0.0177	^81
Utility decrement related to antidepressants w/d	0.085	0.068	0.102	Beta, 0.0210	^82
Somnolence
Share of zuranolone patients experiencing somnolence	36%	26.50%	45.50%	Beta, 0.0758	^47
Share of SSRI patients experiencing somnolence	0%	0%	0%		Assumption
Utility decrement related to somnolence	0.068	0.026	0.152	Beta, 0.0525	^83
Treatment-related Inputs – Treatment Efficacy
Zuranolone change from baseline
Day 3 Δ from baseline	(−2.87)	(−3.66)	(−2.07)	Normal, 0.4000	^62
Day 15 Δ from baseline	(−7.02)	(−8.28)	(−5.76)	Normal, 0.6300
Day 28 Δ from baseline	(−8.33)	(−9.95)	(−6.71)	Normal, 0.8100
Day 45 Δ from baseline	(−9.85)	(−11.23)	(−8.47)	Normal, 0.6900
SSRIs change from baseline
Day 3 Δ from baseline	(−1.96)	(−3.54)	(−0.38)	Normal, 0.8100	^62
Day 15 Δ from baseline	(−2.5)	(−4.37)	(−0.62)	Normal, 0.9600
Day 28 Δ from baseline	(−3.33)	(−5.01)	(−1.64)	Normal, 0.8600
Day 45 Δ from baseline	(−5.75)	(−7.29)	(−4.21)	Normal, 1.1800
Suicide Rate
Health State 1 (0)	0.00%	0.00%	0.00%	Uniform	^65
Health State 2 (1–6)	0.00%	0.00%	0.00%	Uniform
Health State 3 (7–13)	0.00%	0.00%	0.00%	Uniform
Health State 4 (14–18)	0.50%	0.00%	0.90%	Uniform
Health State 5 (19–30)	0.50%	0.00%	0.90%	Uniform
Health Care Costs (Weekly, 2023 USD)
Health care costs excl. drug (mother, < 1 year pp)
Health State 1 (0)	$295.17	$236.14	$354.21	Gamma, 30.12	^39
Health State 2 (1–6)	$295.17	$236.14	$354.21	Gamma, 30.12
Health State 3 (7–13)	$295.17	$236.14	$354.21	Gamma, 30.12
Health State 4 (14–18)	$449.41	$359.52	$539.29	Gamma, 45.86
Health State 5 (19–30)	$449.41	$359.52	$539.29	Gamma, 45.86
Health care costs excl. drug (mother, ≥ 1 year pp)
Health State 1 (0)	$125.13	$100.11	$150.16	Gamma, 12.77	^71
Health State 2 (1–6)	$125.13	$100.11	$150.16	Gamma, 12.77
Health State 3 (7–13)	$125.13	$100.11	$150.16	Gamma, 12.77
Health State 4 (14–18)	$266.99	$213.59	$320.39	Gamma, 27.24
Health State 5 (19–30)	$266.99	$213.59	$320.39	Gamma, 27.24
Health care costs (child, 0–1 years)
Health State 1 (0)	$252.11	$201.69	$302.54	Gamma, 25.73	^41
Health State 2 (1–6)	$252.11	$201.69	$302.54	Gamma, 25.73
Health State 3 (7–13)	$252.11	$201.69	$302.54	Gamma, 25.73
Health State 4 (14–18)	$282.28	$225.82	$338.74	Gamma, 28.80
Health State 5 (19–30)	$282.28	$225.82	$338.74	Gamma, 28.80
Health care costs (child, 2–12 years)
Health State 1 (0)	$17.28	$17.28	$17.28		^40
Health State 2 (1–6)	$17.28	$17.28	$17.28
Health State 3 (7–13)	$17.28	$17.28	$17.28
Health State 4 (14–18)	$30.84	$27.05	$34.33	Gamma, 1.86
Health State 5 (19–30)	$30.84	$27.05	$34.33	Gamma, 1.86
Health care costs (partner)
Health State 1 (0)	$61.18	$61.18	$61.18		^39
Health State 2 (1–6)	$61.18	$61.18	$61.18
Health State 3 (7–13)	$61.18	$61.18	$61.18
Health State 4 (14–18)	$88.30	$70.64	$105.96	Gamma, 9.01
Health State 5 (19–30)	$88.30	$70.64	$105.96	Gamma, 9.01
Health Utilities (Annual)
Health utility (mother)
Health State 1 (0)	0.935	0.895	0.974	Beta, 0.0203	Sage DoF
Health State 2 (1–6)	0.795	0.770	0.819	Log-normal, 0.124
Health State 3 (7–13)	0.659	0.644	0.674	Log-normal, 0.0077
Health State 4 (14–18)	0.573	0.557	0.589	Log-normal, 0.0082
Health State 5 (19–30)	0.520	0.509	0.531	Log-normal, 0.0057
Health utility (child, 0–1 years)
Health State 1 (0)	0.880	0.834	0.926	Beta, 0.0236	^67
Health State 2 (1–6)	0.880	0.834	0.926	Log-normal, 0.0236
Health State 3 (7–13)	0.880	0.834	0.926	Log-normal, 0.0236
Health State 4 (14–18)	0.880	0.834	0.926	Log-normal, 0.0236
Health State 5 (19–30)	0.880	0.834	0.926	Log-normal, 0.0236
Health utility (child, 2–12 years)
Health State 1 (0)	0.875	0.875	0.875		^27^,^67
Health State 2 (1–6)	0.875	0.875	0.875
Health State 3 (7–13)	0.875	0.875	0.875
Health State 4 (14–18)	0.872	0.827	0.917	Log-normal, 0.0230
Health State 5 (19–30)	0.872	0.827	0.917	Log-normal, 0.0230
Health utility (partner)
Health State 1 (0)	0.833	0.833	0.833		^69^,^70
Health State 2 (1–6)	0.833	0.833	0.833
Health State 3 (7–13)	0.833	0.833	0.833
Health State 4 (14–18)	0.820	0.800	0.832	Log-normal, 00084
Health State 5 (19–30)	0.820	0.800	0.832	Log-normal, 0.0084
Indirect Costs (Annual, 2023 USD)
Productivity losses due to illness (mothers)
Labor participation amongst women of childbearing age	100%	62%	100%		^77
Incremental cost of absenteeism attributed to PPD, annual
Health State 1 (0)	$0	$0	$0		^38^,^40^,^42^,^73^,^74
Health State 2 (1–6)	$0	$0	$0
Health State 3 (7–13)	$0	$0	$0
Health State 4 (14–18)	$1,638	$730	$3,153	Gamma, 618.13
Health State 5 (19–30)	$1,638	$730	$3,153	Gamma, 618.13
Incremental cost of presenteeism attributed to PPD, annual
Health State 1 (0)	$0	$0	$0		^40^,^42^,^73^,^74
Health State 2 (1–6)	$0	$0	$0
Health State 3 (7–13)	$0	$0	$0
Health State 4 (14–18)	$5,332	$721	$10,210	Gamma, 2420.92
Health State 5 (19–30)	$5,332	$721	$10,210	Gamma, 2420.92
Increased likelihood of unemployment attributed to PPD (baseline = 4.9%)
Health State 1 (0)	0%	0%	0%		^40
Health State 2 (1–6)	0%	0%	0%
Health State 3 (7–13)	0%	0%	0%
Health State 4 (14–18)	30%	20%	40%	Beta, 0.1000
Health State 5 (19–30)	30%	20%	40%	Beta, 0.1000
Productivity losses due to maternal depression (partners)
Health State 1 (0)	$0	$0	$0		^78
Health State 2 (1–6)	$0	$0	$0
Health State 3 (7–13)	$0	$0	$0
Health State 4 (14–18)	$5,469	$4,375	$6,563	Gamma, 558.07
Health State 5 (19–30)	$5,469	$4,375	$6,563	Gamma, 558.07

Abbreviations: BL, Baseline; DoF, Data on File; ZRN, Zuranolone; MDD, Major Depressive Disorder; PP, Postpartum; PPD, Postpartum Depression; SE, Standard Error; SSRI, Selective Serotonin Reuptake Inhibitor; W/D, Withdrawal; USD, United States Dollar.

Figure 2. Efficacy sources for zuranolone and SSRIs.

^aITC reference: Meltzer-Brody⁶². ^b Observation time points correspond to months 8, 21, and 33, respectively, from Netsi et al.

Abbreviations: EPDS, Edinburgh Postnatal Depression Scale; LOCF, last observation carried forward; PPD, postpartum depression; SSRI, selective serotonin reuptake inhibitor; ZRN, zuranolone; ITC, indirect treatment comparison.

Table 2. Summary of base case results (11-year time horizon).

	Zuranolone	SSRI	Zuranolone vs. SSRI
Direct Costs
Treatment Costs	$15,902	$30	$15,872
Patient’s Health Care Costs	$84,318	$86,365	–$2,047
Child’s Health Care Costs	$28,982	$29,276	–$294
Partner’s Health Care Costs	$20,726	$20,953	–$227
Total Direct Costs	$149,928	$136,624	$13,304
Indirect Costs
Patient’s Absenteeism Costs	$4,227	$4,683	–$456
Patient’s Presenteeism Costs	$13,761	$15,245	–$1,484
Patient’s Lost Wages Due to Unemployment	$2,947	$3,253	–$306
Patient’s Lost Earnings Due to Suicide	$20,728	$23,034	–$2,306
Partner’s Productivity Loss	$8,829	$9,781	–$952
Total Indirect Costs	$50,492	$55,997	–$5,505
Total Costs	$200,420	$192,621	$7,799
Total QALYs
Patient’s Utilities	6.178	6.116	0.062
Child’s Utilities	8.112	8.103	0.009
Partner’s Utilities	7.690	7.679	0.012
Total QALYs	21.981	21.898	0.082
ICER (11-year time horizon)			$94,741

Abbreviations: ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; SSRI, selective serotonin-reuptake inhibitor.

Table 3. Scenario analysis.

Scenario	ZRN Costs	SSRI Costs	ZRN vs. SSRI Costs	ZRN QALYs	SSRI QALYs	ZRN vs. SSRI QALYs	ICER
LOCF^a	$139,832	$185,080	–$45,248	22.420	21.669	0.751	ZRN dominant
Bucher ITC^b	$200,420	$192,647	$7,773	21.981	21.898	0.083	$93,954
Time horizon of 5 years^c	$118,337	$108,227	$10,110	10.972	10.923	0.048	$209,824
Time horizon of 18 years^c	$258,283	$252,045	$6,238	28.797	28.684	0.114	$54,930
Mother’s costs and QALYs only	$141,883	$132,611	$9,272	6.178	6.116	0.062	$149,268

^a As compared to long-term trajectories derived from Netsi et al.

^b As compared to short-term efficacy derived from the NMA.

^c As compared to utilizing an 11-year time horizon.

Abbreviations: ICER, incremental cost-effectiveness ratio; ITC, indirect treatment comparison; LOCF, last observation carried forward; NMA, network meta-analysis; QALY, quality-adjusted life year; SSRI, selective serotonin-reuptake inhibitor; ZRN, zuranolone.

Figure 3. One-way sensitivity analysis.

Note: Change from baseline input values were negative, such that the high value represented the smaller numerical change.

Abbreviations: WTP, willingness-to-pay; QALY, quality-adjusted life year; BL, baseline; PPD, postpartum depression; SSRI, selective serotonin reuptake inhibitor.

Figure 4. Probabilistic sensitivity analysis.

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