Anxiety disorders, major depressive disorder and the dynamic relationship between these conditions: treatment patterns and cost analysis

Figures & data

Figure 1 . Patient selection process.

Table 1. Baseline socio-demographic and medical characteristics according to index diagnosis.

	MDD	Anxiety disorders								Anxiety + MDD
		Panic	SAD	Other phobia	PTSD	OCD	Stress	GAD	Pooled anxiety
N	270,535	19,498	1,236	2,955	3,719	3,141	54,590	212,589	297,728	31,001
Gender (female), %	67.9	65.1	41.2	66.2	65.2	53.7	67.9	64.5	65.0	68.2
P-value*	/	p< 0.001	p< 0.001	p=0.13	p=0.003	p< 0.001	p=0.45	p< 0.001	p< 0.001	p=0.51
Age, mean (SD)	41.6 (13.4)	39.0 (12.5)	32.4 (11.6)	41.5 (12.6)	41.0 (12.5)	36.0 (12.7)	41.1 (11.6)	42.3 (12.9)	41.7 (12.7)	39.5 (12.4)
P-value*	/	p< 0.001	p< 0.001	p=0.71	p=0.01	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001
Region (%)
Northeast	17.4	27.0	20.1	26.3	24.4	25.8	22.3	25.3	24.8	20.6
South	22.5	25.8	16.5	21.8	20.8	22.3	22.9	26.3	25.4	19.3
Midwest	50.4	39.6	58.3	45.3	41.2	44.3	47.4	40.3	41.7	49.1
West	9.7	7.7	5.1	6.6	13.6	7.7	7.4	8.1	8.0	11.0
P-value*	/	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001
Insurance, %
Commercial	89.1	90.5	94.5	90.4	87.9	93.6	93.3	90.0	90.7	89.8
Self-insured	3.3	3.4	2.6	4.2	3.5	3.0	3.0	3.7	3.6	3.1
Medicaid	4.0	3.8	1.5	2.5	6.3	1.5	2.3	3.0	2.9	5.0
Medicare	2.7	1.3	0.2	1.8	0.9	0.9	0.8	2.5	2.1	1.2
Unknown	0.8	0.9	1.2	1.1	1.3	1.0	0.6	0.8	0.8	1.0
P-value*	/	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001
Service provider, %
CDH	0.3	0.4	0.3	0.2	0.4	0.4	0.5	0.3	0.4	0.0
HMO	35.2	32.0	34.4	33.0	35.3	30.1	35.0	32.4	32.9	33.5
Indemnity	6.2	6.0	6.8	6.3	6.4	6.9	5.2	6.2	6.0	6.3
PPO	44.3	46.2	38.1	42.1	42.9	46.9	43.5	45.7	43.9	43.9
Point of service	13.0	14.3	19.1	17.2	13.8	14.5	15.1	14.5	14.6	15.1
Unknown	1.0	1.1	1.3	1.3	1.3	1.1	0.7	0.9	0.9	1.1
P-value*	/	p< 0.001	p< 0.001	p< 0.001	p=0.18	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001
CCI, mean (SD)	0.4 (1.6)	0.3 (1.2)	0.1 (0.7)	0.4 (1.4)	0.4 (1.4)	0.2 (1.1)	0.4 (1.6)	0.4 (1.4)	0.4 (1.5)	0.3 (1.2)
P-value*	/	p< 0.001	p< 0.001	p=0.01	p=0.63	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001

CCI, Charlson Comorbidity Index; CDH, consumer directed healthcare; GAD, generalized anxiety disorder; HMO, health maintenance organization; MDD, major depressive disorder; OCD, obsessive compulsive disorder; PPO, preferred provider organization; PTSD, post-traumatic stress disorder; SAD, social anxiety disorder.

*Statistical comparison with MDD.

Table 2. Antidepressant (AD) and anxiolytic (AX) drugs use according to index diagnosis.

MDD		Anxiety disorders								Anxiety + MDD
		Panic	SAD	Other phobia	PTSD	OCD	Stress	GAD	Pooled anxiety
N	270,535	19,498	1,236	2,955	3,719	3,141	54,590	212,589	297,728	31,001
At index date (% of patients)
AX	1.5	14.0	3.0	12.0	2.0	1.7	4.9	11.5	8.7	8.7
P-value *	/	p< 0.001	p< 0.001	p< 0.001	p=0.01	p=0.41	p< 0.001	p< 0.001	p< 0.001	p< 0.001
AD	13.9	8.7	11.6	5.4	3.6	13.5	4.7	7.8	7.3	16.7
P-value *	/	p< 0.001	p=0.02	p< 0.001	p< 0.001	p=0.55	p< 0.001	p< 0.001	p< 0.001	p< 0.001
AD + AX	0.7	3.0	0.6	1.4	0.4	0.9	0.7	1.5	3.9	3.9
P-value *	/	p< 0.001	p=0.90	p< 0.001	p=0.07	p=0.14	p=0.41	p< 0.001	p< 0.001	p< 0.001
AD or AX	14.7	19.6	13.9	16.1	5.1	14.3	8.9	17.8	21.6	21.6
P-value *	/	p< 0.001	p=0.45	p=0.02	p< 0.001	p=0.52	p< 0.001	p< 0.001	p< 0.001	p< 0.001
During follow-up (% of patients)
AX	9.3	30.3	17.1	34.7	15.7	12.6	20.0	24.7	24.0	20.8
OR *	1	4.7^†	2.4^†	5.7^†	1.9^†	1.6^†	2.6^†	3.4^†	3.3^†	2.6^†
AD	45.2	33.9	55.7	34.6	36.8	56.0	35.1	30.1	31.8	51.5
OR *	1	0.6^†	1.4^†	0.6^†	0.7^†	1.6^†	0.6^†	0.5^†	0.6^†	1.2^†
AD + AX	7.0	16.6	11.5	14.4	8.7	10.2	8.8	10.7	10.8	16.1
AD or AX	47.5	47.6	61.3	54.9	43.9	58.5	46.3	44.1	45.0	56.2
Time to treatment onset (days), mean (median)
AX	116.4 (81)	41.0 (1)	100.4 (42)	58.9 (7)	113.0 (77)	115.2 (77)	94.1 (40)	49.4 (1)	56.7 (2)	62.0 (2)
P-value*	/	p< 0.001	p=0.23	p< 0.001	p=0.57	p=0.94	p< 0.001	p< 0.001	p< 0.001	p< 0.001
AD	46.8 (13)	59.5 (21)	59.8 (25)	81.7 (36)	91.8 (47)	55.3 (20)	92.5 (49)	63.0 (23)	69.2 (27)	42.0 (13)
P-value*	/	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001
AD or AX	48.1 (13)	39.5 (2)	59.7 (22)	57.3 (13)	90.8 (46)	55.9 (19)	86.4 (40)	45.0 (3)	53.4 (7)	38.2 (5)
P-value*	/	p< 0.001	p< 0.001	p=0.002	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001	p< 0.001

*Multivariate logistic regression. MDD was used as reference class.; ^†p was < 0.0001.

AD, antidepressant; AX, anxiolytic; GAD, generalized anxiety disorder; MDD, major depressive disorder; OCD, obsessive compulsive disorder; PTSD, post-traumatic stress disorder; OR, odds ratio; SAD, social anxiety disorder.

Table 3. Healthcare costs ($US), during baseline period and the 1-year follow-up. Results were adjusted for inflation and are presented as mean -[P5; P95].

	MDD	Anxiety disorders								Anxiety + MDD
		Panic	SAD	Other phobia	PTSD	OCD	Stress	GAD	Pooled anxiety
N	270,535	19,498	1,236	2,955	3,719	3,141	54,590	212,589	297,728	31,001
Baseline costs	6,156	4,153 [0;	1,982	5,178	6,882	3,842	6,885	5,132	5,384	4,544
	[0; 21,399]	16,297]	[0; 8,414]	[0; 19,870]	[0; 23,228]	[0; 14,635]	[0; 20,518]	[0; 18,743]	[0; 18,838]	[0; 19,803]
P-value	/	p< 0.001	p< 0.001	p=0.06	p=0.047	p< 0.001	p=0.03	p< 0.001	p< 0.001	p< 0.001
After index date	7,170	5,630	3,772	8,442	8,383	5,272	7,533	6,472	6,631	6,148
	[218; 25,373]	[196; 19,490]	[282; 12,557]	[295; 29,244]	[388; 29,204]	[250; 17,467]	[345; 24,445]	[196; 22,701]	[218; 22,811]	[206; 21,182]
Change, (%)	1,014 (+16.5%)	1,478 (+35.6%)	1,790 (+90.3%)	3,264 (+63.0%)	1,501 (+21.8%)	1,430 (+37.2%)	650 (+9.4%)	1,340 (+26.1%)	1,247 (+23.2%)	1,604 (+35.3%)
RR(p-value)*	1	0.89 (0.001)	0.77 (0.050)	1.14 (0.135)	1.24 (0.005)	0.90 (0.203)	1.01 (0.626)	0.91 (< 0.0001)	0.93 (< 0.0001)	0.98 (0.436)
Detail of cost changes after index date
Inpatient	–307	284 [0; 7,236]	448 [0; 0]	1,321	–648 [0; 11,113]	–162 [0; 4,259]	–940 [0; 8,116]	141 [0; 8,411]	–48 [0; 8,253]	244 [0; 8,419]
	[–3,651; 10,292]			[0; 10,963]
Pharmacy	478	305	372	461	378	510	388	331	379	379
	[–405; 1,820]	[–377; 1,429]	[–245; 1,601]	[–418; 1,803]	[–505; 1,966]	[–336; 2,163]	[–540; 1,666]	[–459; 1,501]	[–466; 1,546]	[–328; 1,621]
Emergency	44.2	90.7	25.2	58.7	26.8	37.6	40.7	63.6	60 [–918; 1,296]	63.9
room	[–738; 1,051]	[–1,207; 1,671]	[–278; 591.3]	[–817; 1,102]	[–1,188; 1,275]	[–574; 846.0]	[–729; 1,045]	[–940; 1,342]		[–794; 1,242]
Home health	26.8 [0.0; 115.4]	8.9 [0.0; 0.0]	2.7 [0.0; 0.0]	–35.7 [0.0; 91.3]	42.5 [0.0; 156.0]	9.4 [0.0; 0.0]	29.3 [0.0; 77.9]	17.2 [0.0; 27.7]	19 [0; 36]	20.5 [0.0; 22.2]
Office visits^†	367.8	344.6	687.6	558.4	861.9	627.4	658.4	289.6	376	437.6
	[–782; 2,064]	[–689; 1,943]	[–377; 2,623]	[–817; 2,710]	[–807; 3,652]	[–582; 2,760]	[–667; 2,902]	[–813; 1,851]	[–776; 2,147]	[–680; 2,264]
Labs	40.7	35.6	32.3	52.3	28.5	14.4	37.4	40.9	40 [–474; 576]	45.7
	[–468; 577.9]	[–465; 562.4]	[–341; 485.2]	[–511; 605.6]	[–541; 604.2]	[–502; 513.2]	[–507; 591.8]	[–465; 573.0]		[–474; 602.2]
Other	363.6	409.4	222.4	848.6	812.2	392.6	435.5	456.9	457	413.2
-outpatient^‡	[–4,917; 6,383]	[–4,305; 5,900]	[–3,056; 3,537]	[–4,520; 8,446]	[–5,364; 8,027]	[–3,380; 5,014]	[–4,997; 6,419]	[–4,722; 6,393]	[–4,726; 6,378]	[–4,238; 5,901]

GAD, generalized anxiety disorder; MDD, major depressive disorder; OCD, obsessive compulsive disorder; PTSD, post-traumatic stress disorder; RR, risk ratio; SAD, social anxiety disorder.

*Multivariate generalized linear model of the healthcare costs after index date, with log link and gamma variance function. MDD was used as reference class. e model was adjusted on baseline costs.

^†General practitioner, psychiatrist, other specialist;

^‡Psychology, psychiatry, other ancillary care.

Table 4. Type of anxiety and treatment according to the concomitance of anxiety and MDD.

	MDD only n=231,017	Anxiety only n=250,532	MDD + anxiety n=31,001	Anxiety then MDD n=47,196	MDD then anxiety n=39,518
Gender (female), %	67.7	64.3	68.2	68.8	69.2
P-value*	/	p< 0.001	p=0.15	p< 0.001	p< 0.001
Age, mean (SD)	41.7 (13.5)	41.9 (12.7)	39.5 (12.4)	40.6 (12.5)	40.5 (12.9)
P-value *	/	p< 0.001	p< 0.001	p< 0.001	p< 0.001
CCI, mean (SD)	0.4 (1.6)	0.4 (1.4)	0.3 (1.2)	0.4 (1.6)	0.4 (1.5)
P-value*	/	p< 0.001	p< 0.001	p< 0.001	p< 0.001
Type of anxiety, n (%)
GAD	/	183,541 (73.3)	23,873 (77.0)	29,048 (61.5)	23,407 (59.2)
Panic	/	16,808 (6.7)	1,798 (5.8)	2,690 (5.7)	2,782 (7.0)
SAD	/	955 (0.4)	364 (1.2)	281 (0.6)	481 (1.2)
Other phobia	/	2,514 (1.0)	433 (1.4)	441 (0.9)	571 (1.4)
PTSD	/	2,641 (1.0)	1,131 (3.6)	1,078 (2.3)	1,710 (4.3)
Stress	/	41,607 (16.6)	2,778 (9.0)	12,983 (27.5)	9,756 (24.7)
OCD	/	2,466 (1.0)	624 (2.0)	675 (1.4)	811 (2.1)
P-value^†	/	/	p< 0.001	p< 0.001	p< 0.001
Treatment 1 year after index date, n (%)
AX	16,577 (7.2)	58,658 (23.4)	6,453 (20.8)	12,823 (27.2)	8,466 (21.4)
OR*^‡	1	4.23	3.48	5.07	3.57
AD	99,832 (43.2)	67,308 (26.9)	15,960 (51.5)	27,264 (57.8)	22,552 (57.1)
OR*^‡	1	0.47	1.33	1.76	1.73
Time to treatment onset (days), mean (median)
AX	117.8 (81)	53.7 (1)	62.0 (2)	70.1 (8)	113.7 (80)
P-value*	/	p< 0.001	p< 0.001	p< 0.001	p=0.04
AD	44.8 (11)	66.0 (23)	42.0 (13)	77.0 (36)	55.4 (19)
P-value*	/	p< 0.001	p< 0.001	p< 0.001	p< 0.001

AD, antidepressant; AX, anxiolytic; GAD, generalized anxiety disorder; MDD, major depressive disorder; OCD, obsessive compulsive disorder; PTSD, post-traumatic stress disorder; OR, odds ratio; SAD, social anxiety disorder.

*Multivariate logistic regression. MDD only was used as reference class;

^†Anxiety only was used as reference class;

^‡p< 0.001 for any cohorts.

Table 5. Annualized (12-month) healthcare costs ($US) according to the MDD/anxiety status, during the 6 months preceding index date and 1-year follow-up. Results were adjusted for inflation and are presented as mean [P5; P95].

	MDD only n=231,017	Anxiety only n=250,532	MDD + anxiety n=31,001	Anxiety then MDD n=47,196	MDD then anxiety n=39,518
Baseline costs	6,066 [0; 21,098]	5,146 [0; 18,228]	4,544 [0; 16,272]	6,648 [0.0; 22,054]	6,688 [0.0; 23,084]
P-value	/	p< 0.001	p< 0.001	p=0.03	p=0.01
After index date	6,681 [196; 24,094]	6,112 [194; 21,244]	6,148 [206; 21,182]	9,387 [495; 31,301]	10,031 [486; 32,959]
Change (%)	615 (+10.1%)	966 (+18.8%)	1,604 (+35.3%)	2,739 (+41.2%)	3,343 (+50.0%)
RR*	1	0.93^†	1.06^†	1.44^†	1.56^†
Detail after index date
Inpatient	2,496 [0; 11,720]	1,915 [0; 8,766]	2,201 [0; 9,448]	3,70 [0; 15,670]	3,977 [0; 17,204]
Pharmacy	926 [0; 3,189]	837 [0; 2,823]	784 [0; 2,681]	1,097 [0; 3,477]	1,536 [0; 3,549]
Emergency room	220 [0; 1,163]	279 [0; 1,477]	276 [0; 1,495]	405 [0; 2,111]	402 [0; 2,018]
Home health	95 [0; 228]	57 [0; 56]	52 [0; 57]	95 [0; 226]	111 [0; 242]
Office visits^‡	816 [65; 2,579]	831 [60; 2,715]	914 [74; 2,923]	1,347 [171; 3,990]	1,325 [171; 3,870]
Labs	196 [0; 761]	193 [0; 760]	200 [0; 788]	239 [0–916]	239 [0; 920]
Other outpatient^§	1,933 [0; 8,186]	2,000 [0; 8,122]	1,721 [0; 7,524]	2,535 [0; 9,892]	2,441 [0; 9,862]

MDD, major depressive disorder; RR, risk ratio.

*Multivariate generalized linear model of the healthcare costs after index date, with log link and gamma variance function. MDD only was used as reference class. e model was adjusted on baseline costs.

^†p was < 0.001 for any condition;

^‡General practitioner, psychiatrist, other specialist; ^§Psychology, psychiatry, other ancillary care.