Factors associated with sick leave duration in patients suffering from major depressive disorder initiating antidepressant treatment: a real-world evidence study in Germany and Spain

Figures & data

Figure 1. Inclusion and exclusion criteria for inclusion in the study cohorts. ¹Index Date: date of first AD prescription during the selection period. ²In the German database, the diagnosis related to the prescription is specified in about 30% of the cases only. ³Selection period: 1 July 2016–30 June 2018. ⁴Study period: 1 July 2015–30 June 2019. ⁵Baseline period: 12-month period preceding the Index Date (excluded). ⁶Follow-up period: 12-month period starting at the Index Date (excluded). AD: antidepressant; MDD: major depressive disorder.

Figure 2. Attrition of study sample. AD: antidepressant; MDD: major depressive disorder; AD MONO: patients who had prescriptions of a single AD both at Index Date and during follow-up; AD COMBI-SW-ADD: patients who had a prescription of more than one AD at Index Date, and patients who had prescriptions of a single AD at Index Date, but received prescriptions of different AD during follow-up.

Table 1. Demographic and clinical characteristics of major depressive disorder (MDD) patients by antidepressant (AD) therapeutic approach.

Characteristic	Germany			Spain
	Total (N = 1,685)	AD MONO (N = 971)	AD COMBI-SW-ADD (N = 714)	Total (N = 1,817)	AD MONO (N = 1,507)	AD COMBI-SW-ADD (N = 310)
Age (years)^a
Mean (SD)	48.1 (10.9)	48.6 (10.7)	47.5 (11.1)	47.9 (11.0)	48.0 (10.9)	47.3 (11.1)
Median [Q1–Q3]	50 [41–57]	51 [42–57]	50 [41–56]	49 [41–57]	49 [41–57]	48 [39–57]
Age class
19–34 years old: n (%)	235 (14.0)	122 (12.6)	113 (15.8)	230 (12.7)	187 (12.4)	43 (13.9)
35–44 years old: n (%)	288 (17.1)	165 (17.0)	123 (17.2)	417 (23.0)	339 (22.5)	78 (25.2)
45–54 years old: n (%)	603 (35.8)	351 (36.2)	252 (35.3)	562 (30.9)	473 (31.4)	89 (28.7)
55–64 years old: n (%)	559 (33.2)	333 (34.3)	226 (31.7)	608 (33.5)	508 (33.7)	100 (32.3)
Sex
Female: n (%)	1003 (59.5)	557 (57.4)	446 (62.5)	1206 (66.4)	1010 (67.0)	196 (63.2)
Baseline comorbidities
Psychiatric
Anxiety: n (%)	93 (5.5)	52 (5.4)	41 (5.7)	315 (17.3)	270 (17.9)	45 (14.5)
Obsessive compulsive disorder^a: n (%)	7 (0.4)	3 (0.3)	4 (0.6)	–	–	–
Bipolar I disorder: n (%)	3 (0.2)	2 (0.2)	1 (0.1)	1 (0.1)	1 (0.1)	.
Substance abuse disorder: n (%)	53 (3.2)	36 (3.7)	17 (2.4)	95 (5.2)	81 (5.4)	14 (4.5)
Schizophrenia: n (%)	42 (2.5)	30 (3.1)	12 (1.7)	4 (0.2)	3 (0.2)	1 (0.3)
Eating disorders: n (%)	7 (0.4)	4 (0.4)	3 (0.4)	1 (0.1)	.	1 (0.3)
Sleeping disorders: n (%)	12 (0.7)	9 (0.9)	3 (0.4)	.	.	.
Headache/migraine: n (%)	70 (4.2)	38 (3.9)	32 (4.5)	58 (3.2)	49 (3.3)	9 (2.9)
Neuropathic pain: n (%)	67 (4.0)	43 (4.4)	24 (3.4)	.	.	.
Non-psychiatric
Obesity: n (%)	7 (0.4)	5 (0.5)	2 (0.3)	22 (1.2)	20 (1.3)	2 (0.7)
Hyperlipidaemia: n (%)	3 (0.2)	3 (0.3)	. (.)	210 (11.6)	181 (12.0)	29 (9.4)
Diabetes: n (%)	6 (0.4)	3 (0.3)	3 (0.4)	115 (6.3)	100 (6.6)	15 (4.8)
Muscular skeletal diseases: n (%)	102 (6.1)	65 (6.7)	37 (5.2)	682 (37.5)	571 (37.9)	111 (35.8)
Hypertension: n (%)	14 (0.8)	13 (1.3)	1 (0.1)	276 (15. 2)	248 (16.5)	28 (9.0)
Coronary artery disease: n (%)	3 (0.2)	1 (0.1)	2 (0.3)	29 (1.6)	26 (1.7)	3 (1.0)
Cerebrovascular disease: n (%)	20 (1.2)	12 (1.2)	8 (1.1)	26 (1.4)	22 (1.5)	4 (1.3)
MDD diagnosis at baseline
Yes: n (%)	472 (28.0)	292 (30.1)	180 (25.2)	387 (21.3)	303 (20.1)	84 (27.1)
MDD severity
Mild: n (%)	97 (5.8)	65 (6.7)	32 (4.5)	–	–	–
Moderate: n (%)	718 (42.6)	409 (42.1)	309 (43.3)		–	–
Severe: n (%)	382 (22.7)	197 (20.3)	185 (25.9)	–	–	–
Unspecified: n (%)	488 (29.0)	300 (30.9)	188 (26.3)	–	–	–

MDD: major depressive disorder; AD: antidepressant; AD MONO: patients who had prescriptions of one single AD molecule both at Index Date and during follow-up; AD COMBI-SW-ADD: patients who were prescribed with more than one AD molecule at Index Date, as well as patients who were prescribed with a single AD molecule at Index Date, but had prescriptions of different AD molecules during follow-up; SD: standard error; Q1: first quartile; Q3: third quartile.

^aIn the ICD-9 coding system, obsessive-compulsive disorder and anxiety disorder are registered under the same code.

Figure 3. Patients were stratified by the number of sick leave days during baseline and follow-up period and the AD therapeutic approach.

Table 2. Results from the multiple logistic regression model estimate the likelihood of having more than 30 days of sick leave during the follow-up period.

Characteristic	Category	Germany			Spain
			95% CI			95% CI
		OR	LL	UL	OR	LL	UL
AD therapeutic approach	AD MONO (ref.)	1.00	–	–	1.00	–	–
	AD COMBI-SW-ADD	2.24^a	1.72	2.92	4.36^a	2.84	6.68
Age—categories	19–34 years old (ref.)	1.00	–	–	1.00	–	–
	35–44 years old	1.22	0.76	1.96	1.36	0.66	2.80
	45–54 years old	0.99	0.65	1.51	0.77	0.36	1.64
	55–64 years old	1.12	0.73	1.72	1.03	0.49	2.19
Sex	Female	1.00	–	–	1.00	–	–
	Male	1.06	0.81	1.39	1.26	0.82	1.94
Baseline anxiety	No (ref.)	1.00	–	–	1.00	–	–
	Yes	0.68	0.36	1.30	1.12	0.63	2.00
Baseline substance abuse disorder	No (ref.)	1.00	–	–	1.00	–	–
	Yes	0.66	0.27	1.61	0.96	0.36	2.57
Baseline schizophrenia^b	No (ref.)	1.00	–	–	–	–	–
	Yes	0.88	0.36	2.16	–	–	–
Baseline headache/migraine^b	No (ref.)	1.00	–	–	–	–	–
	Yes	1.62	0.89	2.93	–	–	–
Baseline neuropathic pain	No (ref.)	1.00	–	–	–	–	–
	Yes	0.57	0.25	1.29	–	–	–
Any other baseline psychiatric comorbidity^c	No (ref.)	–	–	–	1.00	–	–
	Yes	–	–	–	0.46	0.11	2.04
Any baseline non-psychiatric comorbidities^d	No (ref.)	1.00	–	–	1.00	–	–
	Yes	1.15	0.71	1.86	1.22	0.77	1.94
Baseline MDD	No (ref.)	1.00	–	–	1.00	–	–
	Yes	1.38^a	1.03	1.85	6.01^a	3.95	9.16
Severity of MDD	Mild/remission (ref.)	1.00	–	–	–	–	–
	Moderate	1.78	1.00	3.17	–	–	–
	Severe	1.57	0.85	2.89	–	–	–
	Unspecified	1.64	0.90	2.99	–	–	–

AD: antidepressant; AD MONO: patients who had prescriptions of one single AD molecule both at Index Date and during follow-up; AD COMBI-SW-ADD: patients who were prescribed with more than one AD molecule at Index Date, as well as patients who were prescribed with a single AD molecule at Index Date, but had prescriptions of different AD molecules during follow-up; MDD: major depressive disorder; CI: confidence interval; LL: lower limit; UL: upper limit; OR: odds ratio.

^aStatistically significant; p-value <0.05.

^bPresence/absence of this comorbidity was considered by the ‘Any other baseline psychiatric comorbidity’ variable for Spain.

^cThis variable accounted for the presence of at least one psychiatric condition among schizophrenia, bipolar I disorder, headache/migraine in Spain.

^dThis variable accounted for the presence of at least one condition among obesity, hyperlipidaemia, diabetes, muscular skeletal diseases, hypertension, coronary artery disease, cerebrovascular disease in both countries.