Real-World Economic Outcomes of Brexpiprazole and Extended-Release Quetiapine Adjunctive Use in Major Depressive Disorder

Figures & data

Figure 1 Study design.

Abbreviation: Quetiapine XR, Extended-Release Quetiapine.

Figure 2 Sample attrition.

Abbreviations: AAP, Adjunctive Atypical anti-Psychotic; MDD, Major Depressive Disorder; Quetiapine XR, Extended-Release Quetiapine.

Table 1 Baseline Characteristics Before and After Matching

Baseline Characteristics	Non-Matched				Matched
	Brexpiprazole (N=844)	Quetiapine XR (N=688)	P value	SDD	Brexpiprazole (N=397)	Quetiapine XR (N=397)	P value	SDD
Demographic Characteristics
Age in years, mean (SD)	47.2 (12.7)	44.7 (14.4)	0.0002	0.1714	46.3 (12.9)	46.1 (13.8)	0.8406	0.0063
Sex, n (%)
Female	586 (69.4)	464 (67.4)	0.4042	0.0428	265 (66.8)	265 (66.8)	1.0000	0.0000
Geographic region, n (%)			0.0038	0.1879			0.4111	0.0410
Northeast	140 (16.6)	95 (13.8)			56 (14.1)	54 (13.6)
Midwest	246 (29.1)	231 (33.6)			123 (31.0)	118 (29.7)
South	405 (48.0)	293 (42.6)			190 (47.9)	194 (48.9)
West	53 (6.3)	69 (10.0)			28 (7.1)	31 (7.8)
Primary payer^a, n (%)			<0.0001	0.6009			0.8431	0.0645
Commercial	485 (57.5)	328 (47.7)			231 (58.2)	230 (57.9)
Self-insured	328 (38.9)	202 (29.4)			140 (35.3)	135 (34.0)
Medicaid	25 (3.0)	132 (19.2)			22 (5.5)	26 (6.5)
Medicare	5 (0.6)	26 (3.8)			4 (1.0)	6 (1.5)
Other	1 (0.12)	0 (0.0)			0 (0.0)	0 (0.0)
Plan type, n (%)			<0.0001	0.5433			0.1877	0.1022
HMO	65 (7.7)	188 (27.3)			40 (10.1)	51 (12.8)
PPO	374 (87.0)	482 (70.1)			343 (86.4)	336 (84.6)
Other	45 (5.3)	18 (2.6)			14 (3.5)	10 (2.5)
Clinical Characteristics
Index treatment prescriber specialty, n (%)				0.3637				0.0418
Psychiatrist	395 (46.8)	209 (30.4)	<0.0001		156 (39.3)	160 (40.3)	0.7456
Primary care	76 (9.0)	111 (16.1)	<0.0001		45 (11.3)	40 (10.1)	0.4751
Other	373 (44.2)	368 (53.5)	0.0003		196 (49.4)	197 (49.6)	0.9379
CCI, mean (SD)	0.48 (0.98)	0.70 (1.34)	0.0002	−0.1649	0.51 (1.06)	0.52 (1.08)	0.8101	−0.0496
Selected comorbidities, n (%)
Anxiety	472 (55.9)	414 (60.2)	0.0938	−0.0862	229 (57.7)	230 (57.9)	0.9443	−0.0051
Asthma	59 (7.0)	71 (10.3)	0.0200	−0.1186	27 (6.8)	36 (9.1)	0.2249	−0.0840
Diabetes	98 (11.6)	94 (13.7)	0.2277	−0.0618	45 (11.3)	46 (11.6)	0.9081	−0.0079
Epilepsy	14 (1.7)	29 (4.2)	0.0026	−0.1518	6 (1.5)	12 (3.0)	0.1573	−0.1017
Hepatitis/liver disease	4 (0.5)	17 (2.5)	0.0008	−0.0750	2 (0.5)	4 (1.0)	0.3173	0.0294
Hyperlipidemia	229 (27.1)	170 (24.7)	0.2824	0.0553	104 (26.2)	106 (26.7)	0.8703	−0.0114
Hypertension	254 (30.1)	205 (29.8)	0.8991	0.0065	124 (31.2)	110 (27.7)	0.2593	0.0774
Insomnia	81 (9.6)	117 (17.0)	<0.0001	−0.2195	38 (9.6)	66 (16.6)	0.0032	−0.2102
Peripheral vascular disease	4 (0.5)	10 (1.5)	0.0451	−0.1004	1 (0.3)	6 (1.5)	0.0588	−0.1350
Treatment History
No. ADTs used before index, mean (SD)	1.8 (0.9)	1.8 (0.9)	0.0873	0.0803	1.8 (0.9)	1.8 (0.9)	0.6660	−0.0371
Classes of prior ADTs used (n, %)
Tricyclic/tetracyclic	117 (13.9)	131 (19.0)	0.0062	−0.1400	52 (13.1)	79 (19.9)	0.0072	−0.1840
MAOI	9 (1.1)	2 (0.3)	0.0737	0.0946	1 (0.3)	1 (0.3)	1.0000	0.0000
SSRI	382 (45.3)	398 (57.8)	<0.0001	−0.2539	190 (47.9)	224 (56.4)	0.0146	−0.1721
SNRI	390 (46.2)	255 (37.1)	0.0003	0.1863	172 (43.3)	157 (39.5)	0.2948	0.0768
Atypical antidepressant	459 (54.4)	303 (44.0)	<0.0001	0.2080	212 (53.4)	180 (45.3)	0.0280	0.1617
Other antidepressant^b	5 (0.6)	0 (0.0)	0.0432	0.1092	3 (0.8)	0 (0.0)	-	0.1234
Baseline HRU and costs
No. MDD-related ED visits, mean (SD)	0.07 (0.31)	0.12 (0.41)	0.0037	−0.1447	0.09 (0.37)	0.07 (0.30)	0.3594	0.0599
No. MDD-related hospitalizations, mean (SD)	0.09 (0.40)	0.20 (0.55)	<0.0001	−0.2897	0.12 (0.49)	0.10 (0.36)	0.6101	−0.0423
All-cause healthcare cost (US$), mean (SD)	$12,082 ($19,788)	$12,462 ($25,234)	0.7408	0.2793	$11,756 ($22,418)	$12,797 ($29,699)	0.5773	0.2223

Notes: ^aDue to the small number, patients with Medicare, Medicaid, or Other payer types were grouped in the same category for the purpose of propensity score matching. ^bOther antidepressant includes antidepressant fixed dose combination and antidepressant-antipsychotic fixed dose combination.

Abbreviations: ADT, Antidepressant Therapy; HMO, Health Maintenance Organization; PPO, Preferred Provider Organization; POS, Point of Service; CCI, Charlson Comorbidity Index; MAOI, Monoamine Oxidase Inhibitor; MDD, Major Depressive Disorder; SD, Standard Deviation; SDD: Standardized Difference; SSRI, Selective Serotonin Reuptake Inhibitor; SNRI, Serotonin-Norepinephrine Reuptake Inhibitor.

Table 2 Index Dosing and Use of Index Therapy During Follow-Up

Index Treatment	Non-Matched		Matched
	Brexpiprazole (N=844)	Quetiapine XR (N=688)	Brexpiprazole (N=397)	Quetiapine XR (N=397)
Index daily dosing (n, %)
Quetiapine 50 mg		238 (34.6)		140 (35.3)
Quetiapine 100 mg		53 (7.7)		32 (8.1)
Quetiapine 150 mg		209 (30.4)		120 (30.2)
Quetiapine 200 mg		67 (9.7)		40 (10.1)
Quetiapine 300 mg		76 (11.0)		47 (11.8)
Quetiapine 400 mg		25 (3.6)		10 (2.5)
Quetiapine 600 mg		10 (1.5)		4 (1.0)
Other doses^a		10 (1.5)		4 (1.0)
Brexpiprazole 0.125 mg	1 (0.1)		0 (0.0)
Brexpiprazole 0.25 mg	9 (1.1)		5 (1.3)
Brexpiprazole 0.50 mg	100 (11.8)		48 (12.1)
Brexpiprazole 1 mg	384 (45.5)		173 (43.6)
Brexpiprazole 2 mg	330 (39.1)		161 (40.6)
Brexpiprazole 3 mg	11 (1.3)		7 (1.8)
Brexpiprazole 4 mg	9 (1.1)		3 (0.8)
No. fills (including index fill), mean (SD)	3.9 (2.4)	3.7 (2.6)	3.9 (2.3)	3.7 (2.6)
Days of medication supply per fill, mean (SD)	31.4 (7.9)	33.1 (13.2)	31.7 (7.6)	34.0 (14.5)

Note: ^aLess than one percent of patients in the quetiapine XR cohort started the treatment with 25 mg, 75 mg, 450 mg, 800 mg, or 1,200 mg quetiapine XR per day.

Abbreviation: SD, Standard Deviation.

Table 3 Healthcare Resource Utilization Over 6-Month Follow-Up

Resource Utilization	Non-Matched			Matched
	Brexpiprazole (N=844)	Quetiapine XR (N=688)	P value	Brexpiprazole (N=397)	Quetiapine XR (N=397)	P value
Hospitalization
Patients with ≥1 all-cause hospitalization, n (%)	56 (6.6)	86 (12.5)	<0.0001	26 (6.5)	39 (9.8)	0.0924
No. hospital stays, mean (SD)	0.10 (0.43)	0.21 (0.73)	0.0002	0.10 (0.41)	0.14 (0.49)	0.1562
ED visits
Patients with ≥1 all-cause ED visit, n (%)	143 (16.9)	189 (27.5)	<0.0001	74 (18.6)	87 (21.9)	0.2512
No.ED visits, mean (SD)	0.30 (0.96)	0.55 (1.39)	<0.0001	0.33 (1.00)	0.38 (1.16)	0.4920
Physician office visits
Patients with ≥1 all-cause physician office visits, n (%)	827 (98.0)	669 (97.2)	0.3368	388 (97.7)	389 (98.0)	0.8063
No.physician office visits, mean (SD)	14.89 (13.85)	12.57 (13.13)	0.0008	13.47 (11.30)	13.28 (13.65)	0.8341
Pharmacy fills
Patients with ≥1 pharmacy fill, n (%)	844 (100.0)	688 (100.0)	1.0000	397 (100.0)	397 (100.0)	1.0000
No. pharmacy fills, mean (SD)	35.61 (20.56)	35.03 (24.92)	0.6146	34.20 (20.33)	34.06 (24.78)	0.9277

Abbreviations: ED, Emergency Department; SD, Standard Deviation.

Figure 3 Mean healthcare costs over 6-month follow-up (non-matched). (A) Total, medical, and pharmacy costs. (B) Components of medical costs.

Table 4 Regression Analysis Evaluating the Impact of Brexpiprazole vs Quetiapine XR Adjunctive Treatment on Medical Cost and Total Healthcare Cost in The Non-Matched Cohorts

	Medical Cost		Total Healthcare Cost
Variable	Exponentiated Parameter Estimate (95% CI)	P value	Exponentiated Parameter Estimate (95% CI)	P value
Augmented AAP Treatment
Brexpiprazole (ref: quetiapine XR)	0.839 (0.725, 0.971)	0.0186	1.094 (1.001, 1.196)	0.0463
Demographic characteristics
Age	1.006 (1.001, 1.012)	0.0180	1.005 (1.002, 1.008)	0.0018
Female (ref: male)	1.077 (0.933, 1.244)	0.3094	1.077 (0.988, 1.175)	0.0915
Geographic region (ref: South)
Northeast	1.078 (0.881, 1.319)	0.4681	1.045 (0.923, 1.175)	0.4867
Midwest	0.952 (0.812, 1.116)	0.5456	0.898 (0.815, 0.989)	0.0292
West	1.451 (1.113, 1.892)	0.0059	1.211 (1.031, 1.422)	0.0196
Payer type (ref: Commercial)
Employer-sponsored self-insurance	1.032 (0.892, 1.194)	0.6737	1.021 (0.934, 1.115)	0.6512
Other	0.449 (0.321, 0.627)	<0.001	0.680 (0.549, 0.841)	0.0004
Plan type (ref: PPO)
HMO	0.974 (0.727, 1.304)	0.8589	0.928 (0.772, 1.116)	0.4271
Other	0.604 (0.431, 0.847)	0.0034	0.743 (0.605, 0.913)	0.0047
Clinical Characteristics
Index treatment prescriber specialty (ref = Primary care)
Psychiatrist	0.960 (0.773, 1.192)	0.7114	1.018 (0.893, 1.161)	0.7862
Other	1.182 (0.952, 1.467)	0.1304	1.186 (1.040, 1.352)	0.0107
Charlson Comorbidity Index	1.186 (1.108, 1.270)	<0.0001	1.124 (1.077, 1.172)	<0.0001
Comorbid epilepsy (ref: no disease)	0.460 (0.309, 0.683)	0.0001	0.725 (0.569, 0.922)	0.0089
Comorbid asthma (ref: no disease)	0.940 (0.738, 1.198)	0.6187	0.983 (0.847, 1.141)	0.8224
Comorbid hepatitis/liver disease (ref: no disease)	0.657 (0.463, 0.933)	0.0190	0.723 (0.584, 0.895)	0.0029
Comorbid peripheral vascular disease (ref: no disease)	0.896 (0.442, 1.818)	0.7615	0.916 (0.594, 1.413)	0.6911
Treatment History
Prior use of tricyclic/tetracyclic ADT (ref: no prior use)	1.239 (1.033, 1.487)	0.0212	1.111 (0.995, 1.241)	0.0625
Prior use of SSRI ADT (ref: no prior use)	0.993 (0.855, 1.155)	0.9317	0.970 (0.884, 1.064)	0.5152
Prior use of SNRI ADT (ref: no prior use)	1.022 (0.877, 1.192)	0.7766	1.039 (0.945, 1.142)	0.4294
Prior use of atypical ADT (ref: no prior use)	0.973 (0.850, 1.113)	0.6892	0.999 (0.920, 1.085)	0.9876
Baseline HRU and Cost
No. all-cause office visits	1.039 (1.030, 1.048)	<0.0001	1.019 (1.014, 1.024)	<0.0001
No. all-cause ED visits	1.120 (1.036, 1.210)	0.0044	1.036 (0.990, 1.085)	0.1278
No. all-cause hospitalizations	1.545 (1.253, 1.906)	<0.0001	1.110 (0.981, 1.257)	0.0967
No. MDD-related office visits	0.975 (0.964, 0.986)	<0.0001	0.987 (0.980, 0.994)	0.0001
No. MDD-related ED visits	0.883 (0.711, 1.096)	0.2592	0.977 (0.856, 1.116)	0.7352
No. MDD-related hospitalizations	0.957 (0.734, 1.247)	0.7437	1.050 (0.905, 1.219)	0.5178
Pharmacy costs			1.000 (1.000, 1.000)	<0.0001
Medical costs			1.000 (1.000, 1.000)	<0.0001

Abbreviations: ADT, Antidepressant Therapy; AAP, Adjunctive Atypical anti-Psychotics; 95% CI, 95% Confidence Interval; ED, Emergency Department; HMO, Health Maintenance Organization; HRU, Healthcare Resources Utilization; MDD, Major Depressive Disorder; PPO, Preferred Provider Organization; Quetiapine XR, Extended-Release Quetiapine; SSRI, Selective Serotonin Reuptake Inhibitor; SNRI, Serotonin-Norepinephrine Reuptake Inhibitor.

Figure 4 Mean healthcare costs over 6-month follow-up (matched). (A) Total, medical, and pharmacy costs. (B) Components of medical costs.

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available due to the commercially owned, proprietary nature of the datasets, but are available from the corresponding author on reasonable request.