Real-world data analysis of the clinical and economic burden and risk factors in patients with major depressive disorder with an inadequate response to initial antidepressants

Figures & data

Figure 1. Selection criteria for the inclusion of patients in the study cohort.

Table 1. Patients’ baseline demographics and clinical characteristics.

	Total (N = 15,887)		Switching AD (N = 8,270)		Adding AD (N = 6,025)		Adding AAP (N = 1,592)
Age categories, n (%)^a
18–29 years	1,668	(10.50)	598	(7.23)	607	(10.07)	463	(29.08)
30–39 years	1,707	(10.74)	699	(8.45)	759	(12.60)	249	(15.64)
40–49 years	2,453	(15.44)	1,114	(13.47)	1,084	(17.99)	255	(16.02)
50–59 years	3,298	(20.76)	1,764	(21.33)	1,318	(21.88)	216	(13.57)
60–69 years	3,269	(20.58)	1,911	(23.11)	1,177	(19.54)	181	(11.37)
≥70 years	3,492	(21.98)	2,184	(26.41)	1,080	(17.93)	228	(14.32)
Male, n (%)^a	6,382	(40.17)	3,284	(39.71)	2,354	(39.07)	744	(46.73)
Female, n (%)	9,505	(59.83)	4,986	(60.29)	3,671	(60.93)	848	(53.27)
CCI score, n (%)^a
CCI = 0	5,735	(36.10)	2,603	(31.48)	2,290	(38.01)	842	(52.89)
CCI = 1	3,569	(22.46)	1,843	(22.29)	1,402	(23.27)	324	(20.35)
CCI = 2	2,459	(15.48)	1,332	(16.11)	952	(15.80)	175	(10.99)
CCI ≥ 3	4,124	(25.96)	2,492	(30.13)	1,381	(22.92)	251	(15.77)
Mental comorbidity, n (%)
Anxiety disorders^a	5,807	(36.55)	2,848	(34.44)	2,346	(38.94)	613	(38.51)
Obsessive disorder^a	255	(1.61)	67	(0.81)	95	(1.58)	93	(5.84)
Personality disorder^a	107	(0.67)	34	(0.41)	37	(0.61)	36	(2.26)
Insomnia^a	2,302	(14.49)	934	(11.29)	1,149	(19.07)	219	(13.76)
Hospital category at the index date, n (%)^a
Tertiary hospitals	8,615	(54.23)	4,508	(54.51)	3,208	(53.24)	899	(56.47)
General hospitals	1.315	(8.28)	667	(8.07)	486	(8.07)	162	(10.18)
Clinics	5,957	(37.50)	3,095	(37.42)	2,331	(38.69)	531	(33.35)
Specialty at the index date, n (%)^a
Psychiatry	7,981	(50.24)	3,093	(37.40)	3,644	(60.48)	1,244	(78.14)
Neurology	116	(0.73)	69	(0.83)	40	(0.66)	7	(0.44)
Internal medicine	2,766	(17.41)	1,788	(21.62)	859	(14.26)	119	(7.47)
Others	5,024	(31.62)	3,320	(40.15)	1,482	(24.60)	222	(13.94)
Year of index date, n (%)^b
2013	4,845	(30.50)	2,541	(30.73)	1,872	(31.07)	432	(27.14)
2014	7,947	(50.02)	4,152	(50.21)	2,992	(49.66)	803	(50.44)
2015	3,095	(19.48)	1,577	(19.07)	1,161	(19.27)	357	(22.42)

Abbreviations. AD, antidepressant; AAP, typical antipsychotics; CCI, Charlson comorbidity index.

p-values were calculated using the chi-squared test or Fisher's exact test for categorical variables, as appropriate.

^ap-value < .0001; ^b0.01< p-value < .05

Table 2. Details regarding treatment-resistant depression, psychiatric conditions, healthcare resource use, and cost.

	Total (N = 15,887)	Switching AD (N = 8,270)	Adding AD (N = 6,025)	Adding AAP (N = 1,592)
Treatment-resistant depression for 2 years
Incidence, n (%)^a	2,670 (16.81)	1,169 (14.14)	1,184 (19.65)	317 (19.91)
Psychiatric conditions for 2 years, n (%)
Dementia^a	1,409 (8.87)	802 (9.70)	419 (6.95)	188 (11.81)
Schizophrenia^a	1,212 (7.63)	350 (4.23)	312 (5.18)	550 (34.55)
Bipolar disorders^a	2,076 (13.07)	740 (8.95)	648 (10.76)	688 (43.22)
Anxiety disorders	11,125 (70.03)	5,793 (70.05)	4,222 (70.07)	1,110 (69.72)
Obsessive-compulsive disorder^a	496 (3.12)	163 (1.97)	182 (3.02)	151 (9.48)
Personality disorders^a	278 (1.75)	87 (1.05)	89 (1.48)	102 (6.41)
Substance use disorders^a	507 (3.19)	194 (2.35)	238 (3.95)	75 (4.71)
Insomnia^a	5,267 (33.15)	2,456 (29.70)	2,267 (37.63)	544 (34.17)
Healthcare resource use for 2 years
Hospitalization, n (%)^a	7,241 (45.58)	3,973 (48.04)	2,579 (42.80)	689 (43.28)
Inpatient days, mean ± SD^a	21.28 ± 81.74	20.68 ± 75.77	18.73 ± 78.47	34.08 ± 115.60
Outpatient visits, mean ± SD^a	83.98 ± 64.93	87.82 ± 66.57	82.98 ± 64.55	67.83 ± 54.27
ER visits, mean ± SD	0.21 ± 1.11	0.23 ± 1.23	0.20 ± 1.01	0.17 ± 0.75
Medical costs (KRW) in 3^rd year, mean ± SD
Patients, n (%)	8,942 (56.29)	4,743 (57.35)	3,382 (56.13)	817 (51.32)
Total cost	3,098,106 ± 6,789,400	3,106,268 ± 6,821,575	3,052,568 ± 6,539,841	3,239,221 ± 7,577,445
Psychiatry-related cost^a	439,289 ± 1,609,323	342,811 ± 1,371,521	462,753 ± 1,511,229	902,256 ± 2,777,215
Depression-related drug cost^a	127,312 ± 210,788	93,182 ± 163,735	141,966 ± 197,711	264,787 ± 377,496

Abbreviations. AD, antidepressant; AAP, atypical antipsychotics; TRD, treatment-resistant depression; SD, standard deviation; ER, emergency room; KRW, Korean won.

p-values were calculated using ANOVA for continuous variables and the chi-squared test or Fisher's exact test for categorical variables, as appropriate.

^ap-value < .0001.

Table 3. Risk of TRD and psychiatric conditions for the first 2 years.

	Odds ratio (95% CI)
	TRD	Psychiatric conditions
Treatment in 2^nd regimen (ref: switching AD)
Adding AD	1.43 (1.30 − 1.56)	1.06 (0.98 − 1.16)
Adding AAP	1.42 (1.23 − 1.65)	1.05 (0.91 − 1.22)
TRD (ref: none)
TRD onset	–	1.40 (1.25 − 1.57)
Mental comorbidity (ref: none)
Anxiety disorders	1.10 (1.01 − 1.20)	–
Obsessive-compulsive disorder	1.03 (0.75 − 1.42)	–
Personality disorders	1.12 (0.69 − 1.80)	–
Insomnia	1.20 (1.06 − 1.36)	–
Age (ref: 18–29)
30–39	0.99 (0.83 − 1.19)	1.05 (0.88 − 1.26)
40–49	0.95 (0.81 − 1.13)	1.21 (1.03 − 1.44)
50–59	0.94 (0.79 − 1.11)	1.21 (1.03 − 1.43)
60–69	0.95 (0.80 − 1.13)	1.14 (0.97 − 1.35)
≥70	0.82 (0.69 − 0.97)	1.13 (0.96 − 1.33)
Gender (ref: male)
Female	0.95 (0.87 − 1.03)	1.12 (1.04 − 1.22)
Depression severity (ref: mild)
Moderate	1.01 (0.85 − 1.20)	0.93 (0.79 − 1.10)
Severe without psychotic symptoms	0.87 (0.67 − 1.11)	1.23 (0.97 − 1.57)
Severe with psychotic symptoms	0.99 (0.48 − 2.07)	0.75 (0.40 − 1.42)
Unknown	1.00 (0.87 − 1.15)	1.54 (1.35 − 1.74)
CCI score (ref: CCI = 0)
CCI = 1	1.00 (0.89 − 1.13)	1.15 (1.03 − 1.28)
CCI = 2	0.99 (0.86 − 1.13)	1.15 (1.01 − 1.30)
CCI ≥ 3	1.11 (0.98 − 1.25)	1.19 (1.06 − 1.34)
Hospital category at index date (ref: tertiary)
General hospitals	0.82 (0.70 − 0.97)	0.92 (0.80 − 1.06)
Clinics	0.91 (0.83 − 1.00)	1.42 (1.30 − 1.56)
Specialty at index date (ref: psychiatry)
Neurology	0.67 (0.38 − 1.18)	0.43 (0.28 − 0.66)
Internal medicine	0.91 (0.80 − 1.05)	0.43 (0.38 − 0.48)
Others	0.95 (0.85 − 1.06)	0.41 (0.37 − 0.45)
Year of index date (ref: 2013)
2014	0.98 (0.89 − 1.08)	0.93 (0.85 − 1.02)
2015	1.06 (0.94 − 1.20)	0.99 (0.88 − 1.11)

Abbreviations. TRD, treatment-resistant depression; CI, confidence interval; CCI, Charlson comorbidity index; AD, antidepressant; AAP, atypical antipsychotic

Values in bold represent p value <0.05.

Table 4. Risk regarding healthcare resource use and cost.

	Odds ratio (95% CI)	Relative ratio (95% CI)
	Hospitalization	Inpatient days	Total cost
Treatment in 2^nd regimen (ref: switching AD)
Adding AD	0.97 (0.90 − 1.04)	0.92 (0.73 − 1.15)	1.04 (0.95 − 1.14)
Adding AAP	1.25 (1.11 − 1.41)	2.57 (1.75 − 3.76)	1.20 (1.02 − 1.40)
TRD (ref: none)
TRD onset	1.14 (1.05 − 1.25)	1.61 (1.22 − 2.14)	1.28 (1.15 − 1.43)
Mental comorbidity (ref: None)
Anxiety disorders	0.93 (0.87 − 1.00)	0.73 (0.58 − 0.91)	0.95 (0.87 − 1.04)
Obsessive-compulsive disorder	0.69 (0.51 − 0.92)	0.34 (0.14 − 0.80)	1.21 (0.86 − 1.70)
Personality disorders	0.81 (0.53 − 1.24)	0.66 (0.18 − 2.42)	1.31 (0.75 − 2.28)
Insomnia	1.19 (1.08 − 1.32)	1.83 (1.33 − 2.52)	1.31 (1.16 − 1.49)
Age (ref: 18-29)
30–39	1.06 (0.91 − 1.23)	1.12 (0.70 − 1.77)	1.55 (1.28 − 1.88)
40–49	1.08 (0.94 − 1.24)	1.17 (0.76 − 1.81)	1.75 (1.46 − 2.09)
50–59	1.29 (1.13 − 1.48)	2.12 (1.38 − 3.25)	2.39 (2.01 − 2.84)
60–69	1.42 (1.24 − 1.63)	3.17 (2.04 − 4.91)	3.26 (2.73 − 3.89)
≥70	1.89 (1.64 − 2.17)	8.54 (5.48 − 13.30)	3.50 (2.93 − 4.19)
Gender (ref: Male)
Female	1.05 (0.98 − 1.12)	1.16 (0.93 − 1.44)	1.00 (0.92 − 1.09)
Depression severity (ref: mild)
Moderate	1.11 (0.97 − 1.28)	1.29 (0.83 − 2.02)	1.00 (0.84 − 1.19)
Severe without psychotic symptoms	1.28 (1.05 − 1.55)	1.95 (1.05 − 3.63)	1.02 (0.79 − 1.31)
Severe with psychotic symptoms	0.55 (0.29 − 1.06)	0.22 (0.03 − 1.43)	1.38 (0.70 − 2.75)
Unknown	1.13 (1.02 − 1.26)	1.46 (1.04 − 2.07)	0.96 (0.83 − 1.10)
CCI Score (ref: CCI = 0)
CCI = 1	1.24 (1.13 − 1.36)	1.94 (1.45 − 2.59)	1.33 (1.19 − 1.49)
CCI = 2	1.39 (1.25 − 1.54)	2.99 (2.14 − 4.20)	1.61 (1.41 − 1.85)
CCI ≥ 3	1.86 (1.69 − 2.05)	9.26 (6.78 − 12.68)	2.15 (1.90 − 2.43)
Hospital category at index date (ref: tertiary)
General hospitals	1.24 (1.09 − 1.39)	2.52 (1.70 − 3.73)	0.93 (0.79 − 1.09)
Clinics	0.66 (0.62 − 0.72)	0.26 (0.20 − 0.33)	0.99 (0.90 − 1.09)
Specialty at index date (ref: psychiatry)
Neurology	1.45 (0.99 − 2.11)	4.36 (1.25 − 15.18)	1.26 (0.77 − 2.06)
Internal medicine	1.71 (1.54 − 1.89)	6.50 (4.62 − 9.13)	1.25 (1.10 − 1.43)
Others	1.45 (1.33 − 1.58)	4.00 (3.01 − 5.31)	1.04 (0.93 − 1.17)
Year of index date (ref: 2013)
2014	0.91 (0.84 − 0.98)	0.68 (0.53 − 0.88)	–
2015	0.94 (0.86 − 1.04)	0.71 (0.52 − 0.97)	–

Abbreviations. TRD, treatment-resistant depression; CI, confidence interval; CCI, Charlson comorbidity index; AD, antidepressant; AAP, atypical antipsychotic.

Values in bold represent p value <0.05.

Data availability statement

The data that support the findings of this study are available from the authors upon reasonable request and with permission from the Health Insurance Review and Assessment Service (HIRA) in the Republic of Korea.