Treatment persistence, healthcare utilisation and costs in adult patients with major depressive disorder: a comparison between escitalopram and other SSRI/SNRIs

Figures & data

Figure 1. Sensitivity analysis – Comparison of healthcare costs per patient between escitalopram and other SSRI/SNRIs during the study period.

Table 1. Sample selection process.

Step	Description	n (%)
1	Identify patients with at least one inpatient claim or two independent medical claims associated with an MDD diagnosis between January 1, 2003 and June 30, 2005	266,739
2	Keep patients who filled at least one prescription for escitalopram or other SSRI/SNRIs (the first fill date was defined as the index date)	182,200 (68.3%)
3	Exclude patients with 2nd-generation antidepressant use during the 6-month period prior to the index date	105,251 (39.5%)
4	Keep patients with at least 12 months of continuous eligibility, including 6 months prior to the index date (baseline period) and 6 months after the index date (study period)	48,354 (18.1%)
5	Keep patients aged 18 or older	41,760 (15.7%)
6	Keep patients without other 2nd-generation antidepressant use within 2 weeks after the index date (to exclude cases on combination therapies)	38,775 (14.5%)

Table 2. Diagnosis code(s) for conditions considered.

Condition	Diagnosis code(s)
Major depressive disorder (MDD)	296.2x (Major depressive disorder, single episode); 296.3x (Major depressive disorder, recurrent episode)
Dementia and Alzheimer's disease	290.xx (Dementias); 291.2x (Alcohol-induced persisting dementia); 292.82 (Drug-induced persisting dementia); 294.1x (Dementia in conditions classified elsewhere); 294.8x (Other persisting mental disorders due to conditions classified elsewhere); 331.0x (Alzheimer's disease); 331.1x (Frontotemporal dementia)
Generalised anxiety disorder	300.02 (Generalised anxiety disorder)
Obsessive-compulsive disorder	300.3x (Obsessive-compulsive disorders)
Other psychotic disorders	293.81 (Psychotic disorder with delusions in conditions classified elsewhere); 293.82 (Psychotic disorder with hallucinations in conditions classified elsewhere); 297.1x (Delusional disorder); 297.3x (Shared psychotic disorder); 298.8x (Other and unspecified reactive psychosis); 298.9x (Unspecified psychosis)
Panic disorder	300.01 (Panic disorder without agoraphobia)
Phobia	300.2x (Phobic disorders)
Post-traumatic stress disorder	309.81 (Post-traumatic stress disorder)
Schizophrenia	295.xx (Schizophrenic disorders)
Sleeping disorder	307.42 (Persistent disorder of initiating or maintaining sleep); 307.44 (Persistent disorder of initiating or maintaining wakefulness); 307.45 (Circadian rhythm sleep disorder of nonorganic origin); 307.46 (Sleep arousal disorder); 307.47 (Other dysfunctions of sleep stages or arousal from sleep); 347.xx (Cataplexy and narcolepsy); 780.52 (Insomnia, unspecified); 780.54 (Hypersomnia, unspecified); 780.59 (Other sleep disturbances)
Cancer	140–195 (Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphatic and hematopoietic tissue); 196–198 (Malignant neoplasms, stated or presumed to be secondary, of specified sites); 199 (Malignant neoplasms, without specification of site); 200–208 (Malignant neoplasms, stated or presumed to be primary, of lymphatic and hematopoietic tissue)
Cardiovascular disease	306.2x (Physiological malfunction arising from mental factors – Cardiovascular); 394.xx (Diseases of mitral valve); 395.xx (Diseases of aortic valve); 396.xx (Diseases of mitral and aortic valves); 397.xx (Diseases of other endocardial structures); 398.xx (Other rheumatic heart disease); 402.xx (Hypertensive heart disease); 410.xx – 414.xx (Ischemic heart disease); 415.xx – 417.xx (Diseases of pulmonary circulation); 420.xx – 429.xx (Other forms of heart disease); 431.xx (Intracerebral hemorrhage); 434.xx (Occlusion of cerebral arteries); 436.xx (Acute, but ill-defined, cerebrovascular disease); 437.xx (Other and ill-defined cerebrovascular disease); 746.xx (Other congenital anomalies of heart)
Chronic obstructive pulmonary disease and allied conditions	490.xx (Bronchitis, not specified as acute or chronic); 491.xx (Chronic bronchitis); 492.xx (Emphysema); 493.xx (Asthma); 494.xx (Bronchiectasis); 496.xx (Chronic airway obstruction, not elsewhere classified)
Diabetes	250.xx (Diabetes mellitus)
Epilepsy	333.2x (Myoclonus); 345.xx (Epilepsy and recurrent seizures)
Hyperlipidemia	272.0x (Pure hypercholesterolemia); 272.1x (Pure hyperglyceridemia); 272.2x (Mixed hyperlipidemia); 272.3x (Hyperchylomicronemia); 272.4x (Other and unspecified hyperlipidemia)
Hypertension	401.xx – 405.xx (Hypertensive disease); 416.0x (Primary pulmonary hypertension); 416.8x (Other chronic pulmonary heart diseases); 437.2x (Hypertensive encephalopathy); 459.1x (Postphlebitic syndrome); 459.3x (Chronic venous hypertension [idiopathic]); 642.xx (Hypertension complicating pregnancy, childbirth, and the puerperium)
Irritable bowel syndrome	564.1x (Irritable bowel syndrome)
Renal disease	250.4x (Diabetes with renal manifestations); 403.xx (Hypertensive chronic kidney disease); 404.xx (Hypertensive heart and chronic kidney disease); 581.9x (Nephrotic syndrome with unspecified pathological lesion in kidney); 582.xx (Chronic glomerulonephritis); 583.xx (Nephritis and nephropathy, not specified as acute or chronic); 584.xx (Acute renal failure); 585.xx (Chronic kidney disease [CKD]); 586.xx (Renal failure, unspecified); 587.xx (Renal sclerosis, unspecified); 588.xx (Disorders resulting from impaired renal function); 593.9x (Unspecified disorder of kidney and ureter); 646.2x (Unspecified renal disease in pregnancy, without mention of hypertension); 753.11 (Congenital single renal cyst); 753.15 (Renal dysplasia)
Rheumatoid arthritis and osteoarthritis	714.xx (Rheumatoid arthritis and other inflammatory polyarthropathies); 715.xx (Osteoarthrosis and allied disorders)
Stroke	431.xx (Intracerebral hemorrhage); 434.xx (Occlusion of cerebral arteries); 436.xx (Acute, but ill-defined, cerebrovascular disease)

Table 3. Sample count by index therapy.

Index therapy	Patient count
Escitalopram	10,465
Other SSRI/SNRIs	28,310 (100%)
Sertraline	8,132 (28.7%)
Fluoxetine	5,594 (19.8%)
Paroxetine	5,504 (19.4%)
Venlafaxine	4,534 (16.0%)
Citalopram	4,212 (14.9%)
Duloxetine	176 (0.6%)
Fluvoxamine	158 (0.6%)
Grand Total	38,775

Table 4. Comparison of baseline characteristics of adult MDD patients treated with escitalopram versus other SSRI/SNRIs.

Baseline characteristics*	Escitalopram	Other SSRI/SNRIs	p-value^†
	(n=10,465)	(n=28,310)
Demographic characteristics
Mean [SD] age on index date	41.7 [13.7]	41.6 [14.1]	0.269
Age group^‡ (%)			0.001**
18–40 years	47.6	48.3
41–55 years	36.9	35.5
56–64 years	11.1	10.8
65–70 years	1.4	1.6
71–75 years	1.0	1.2
76–80 years	2.0	2.5
Female (%)	67.5	69.5	<0.001**
Comorbidities
Mean [SD] Deyo–Charlson Comorbidity Index	0.8 [2.0]	0.8 [2.2]	0.082
Mental diseases (%)
Dementia and Alzheimer's disease	0.6	0.6	0.786
Generalised anxiety disorder	6.2	4.8	<0.001**
Obsessive-compulsive disorder	1.1	1.1	0.740
Other psychotic disorders	1.0	1.1	0.424
Panic disorder	3.1	2.7	0.030**
Phobia	1.2	1.3	0.519
Post-traumatic stress disorder	2.1	2.0	0.608
Schizophrenia	0.5	0.6	0.124
Sleeping disorder	4.4	3.7	<0.001**
Other diseases (%)
Cancer	3.2	3.8	0.004**
Cardiovascular disease	9.3	9.4	0.781
Chronic obstructive pulmonary disease    and allied conditions	8.7	8.8	0.818
Diabetes	5.4	5.6	0.403
Epilepsy	0.8	0.7	0.224
Hyperlipidaemia	14.4	13.0	<0.001**
Hypertension	14.3	14.3	0.849
Irritable bowel syndrome	1.9	1.9	0.879
Renal disease	1.3	1.4	0.273
Rheumatoid arthritis and osteoarthritis	4.8	4.7	0.641
Stroke	0.9	1.0	0.438
Healthcare utilisation
Mean [SD] number of prescription drugs	4.54 [4.65]	4.40 [4.59]	<0.001**
Other services (%)
Inpatient visit	13.5	14.5	0.012**
Outpatient hospital visit	54.5	55.9	0.014**
Office visit	94.1	92.3	<0.001**
ER visit	22.0	22.6	0.169

*Baseline characteristics were measured during the 6-month pre-index period.

**p<0.05.

†Wilcoxon rank sum test was used for continuous variables; Pearson chi-square test was used for categorical variables.

^‡80 is the oldest age in the study sample.

MDD, major depressive disorder;

SD, standard deviation.

Table 5. Comparison of persistence and healthcare utilisation between escitalopram and other SSRI/SNRIs.

Outcomes*	Escitalopram (n=10,465)	Other SSRI/SNRIs (n=28,310)	Adjusted HR, OR or IRR^† and 95% CI
Discontinuation, n (%)
All discontinuation^‡	6,049 (57.8%)	16,760 (59.2%)	0.96 (0.94, 0.99)**
Discontinuation with switching^‡	2,585 (24.7%)	7,559 (26.7%)	0.91 (0.87, 0.94)**
Healthcare utilisation
Use of inpatient place of service
All-cause (any reason), n (%)^§	1,214 (11.6%)	3,765 (13.3%)	0.86 (0.80, 0.93)**
Mean [SD] number of days, any reason^††	1.0 (5.1)	1.3 (6.5)	0.69 (0.62, 0.77)**
MDD-related, n (%)^§	419 (4.0%)	1,274 (4.5%)	0.89 (0.80, 1.00)
Mean [SD] number of days, MDD-related^††	0.3 (2.1)	0.4 (2.9)	0.67 (0.56, 0.81)
ER visit, for any reason, n (%)^§	2,072 (19.8%)	6,426 (22.7%)	0.84 (0.79, 0.89)**
ER visit, MDD-related, n (%)^§	126 (1.2%)	453 (1.6%)	0.73 (0.59, 0.89)**
Mean [SD] number of ER visits, any cause^††	0.3 (1.1)	0.4 (1.1)	0.85 (0.80, 0.89)**

*All outcomes were observed during the 6-month post-index period.

^†All ratios were adjusted for the baseline characteristics.

^‡Hazard ratio was used for comparison; adjustment based on Cox proportional hazards model.

^§Odds ratio was used for comparison; adjustment based on logistic regression.

**p<0.05 based on Wilcoxon tests for continuous variables and chi-square tests for categorical variables.

^††Incidence rate ratio was used for comparison; adjustment based on negative binomial model.

HR, hazard ratio; OR, odds ratio; IRR, incidence rate ratio; SD, standard deviation; CI, confidence interval.

Table 6. Post-discontinuation healthcare utilisation among patients who discontinued without switching.

Healthcare utilisation*	Escitalopram (n=3,467)	Other SSRI/SNRIs (n=9,214)	p-value^†
25th percentile of the time to a hospitalisation (days)^‡	709	573	0.016
Median time to an ER visit (days)	794	731	<0.001

*Healthcare utilisation outcomes were examined over the period from the first day post-discontinuation of the index drug to the end of the continuous enrolment; average follow-up time was 502 days (standard deviation = 208; median = 483; range = 181–955).

^†p-values were calculated based on log-rank tests.

^‡Median time to hospitalisation is not reported because fewer than 50% of patients who discontinued without switching had a subsequent hospitalisation event before being censored.

Table 7. Comparison of overall and MDD-related healthcare costs between escitalopram and other SSRI/SNRIs.

6-month healthcare costs*	Escitalopram (n=10,465)		Other SSRI/SNRIs (n=28,310)		Difference
	Mean [SD] Median	Range	Mean [SD] Median	Range	Mean difference	Adjusted difference^†
Total healthcare cost	5,551 (12,772) 2,584	(29, 314,540)	6,304 (18,349) 2,693	(7, 1,031,723)	–753**	–839**
Total healthcare cost, MDD related	1,006 (2,297) 556	(4, 95,720)	1,129 (2,812) 616	(3, 209,298)	–123**	–122**
Total prescription drug^‡	1,142 (1,715) 675	(11, 60,130)	1,209 (2,341) 734	(3, 258,367)	–67**	–117**
Total antidepressant cost	326 (217) 313	(4, 4,743)	393 (317) 352	(3, 5,302)	–67**	–67**
Total medical services^§	4,410 (12,247) 1,629	(0, 312,973)	5,095 (17,741) 1,704	(0, 1,029,209)	–685**	–739**
Total medical services,   MDD Related	680 (2,264) 211	(0, 95,360)	735 (2,772) 193	(0, 209,274)	–55**	–32**
Professional services	1,885 (2,529) 1,230	(0, 98,148)	1,959 (2,915) 1,238	(0, 173,208)	–74	–78**
Professional services, MDD related	472 (908) 193	(0, 31,619)	467 (987) 163	(0, 40,224)	5**
Hospitalisation	1,127 (7,589) 0	(0, 269,619)	1,521 (12,648) 0	(0, 984,873)	–394**	–405**
Hospitalisation, MDD related	174 (1,903) 0	(0, 94,010)	227 (2,282) 0	(0, 202,974)	–53**	—
Outpatient visit	786 (2,910) 0	(0, 91,620)	859 (4,521) 34	(0, 432,191)	–73**	–9**
Outpatient visit, MDD related	26 (290) 0	(0, 14,999)	29 (281) 0	(0, 14,387)	–3**	—
ER visit	106 (495) 0	(0, 19,827)	127 (526) 0	(0, 30,918)	–21**	–1**
ER visit, MDD related	5 (62) 0	(0, 2,708)	6 (63) 0	(0, 2,160)	–1**	—

*Costs were measured during the 6-month post-index study period. All numbers were the average costs per patient.

^†Adjustment for all baseline characteristics. For hospitalisation cost, a two-part model was used; for other costs, GLM with log link and gamma distribution was used.

^‡Total prescription drug costs included total antidepressant costs and other prescription drug costs; other prescription drug costs were not presented in this table.

^§Total medical services included professional services, hospitalisations, outpatient visits, ER visits and other medical services; other medical services were not presented in this table.

**p<0.05 based on Wilcoxon tests for the unadjusted differences and GLM or two-part model for the adjusted differences.

GLM, generalised linear model; ER, emergency room; MDD, major depressive disorder; SD, standard deviation.