Relationship between use of selective serotonin reuptake inhibitors and irritable bowel syndrome: A population-based cohort study

Table 1 Baseline characteristics of the selective serotonin reuptake inhibitor cohort and the non-selective serotonin reuptake inhibitor cohort, 2000-2010 n (%)

Variable	SSRI use		P value
	No (n = 78612)	Yes (n = 19653)
Sex			1.000
Female	45984 (58.5)	11496 (58.5)
Male	32628 (41.5)	8157 (41.5)
Age, yr			1.000
< 20	5548 (7.1)	1387 (7.1)
20-29	11592 (14.8)	2898 (14.8)
30-39	14312 (18.2)	3578 (18.2)
40-49	15112 (19.2)	3778 (19.2)
50-59	11720 (14.9)	2930 (14.9)
≥ 60	20328 (25.9)	5082 (25.9)
Urbanization1			< 0.001
1	24102 (31.3)	6275 (32.7)
2	23134 (30.0)	5851 (30.5)
3	12486 (16.2)	2827 (14.7)
4	17325 (22.5)	4228 (22.0)
Family income (NTD)			< 0.001
0	13932 (17.7)	3411 (17.4)
1-15840	14871 (18.9)	4807 (24.5)
15841-28800	33687 (42.9)	7915 (40.3)
28801-45800	10243 (13.0)	2173 (11.1)
≥ 45801	5874 (7.5)	1346 (6.9)
Area			< 0.001
North	39708 (50.6)	10001 (51.0)
Midland	14067 (17.9)	3265 (16.7)
South	22823 (29.1)	5642 (28.8)
East	1837 (2.3)	690 (3.5)
Occupation			< 0.001
Public and military	5735 (8.2)	1531 (8.8)
Industry	23168 (33.3)	5617 (32.3)
Business	28266 (40.6)	5841 (33.6)
Low income	559 (0.8)	385 (2.2)
Other and retired	11898 (17.1)	3994 (23.0)
Anti-psychotics			< 0.001
No	75615 (96.2)	16022 (81.5)
Yes	2997 (3.8)	3631 (18.5)
Comorbidity
Diabetes mellitus	8126 (10.3)	3143 (16.0)	< 0.001
Hypertension	18319 (23.3)	6726 (34.2)	< 0.001
Hyperlipidemia	11823 (15.0)	4521 (23.0)	< 0.001
Colorectal cancer	290 (0.4)	96 (0.5)	0.017
Major depressive disorder	770 (0.98)	4274 (21.8)	< 0.001
Anxiety disorder	10007 (12.7)	9477 (48.2)	< 0.001
Bipolar disorder	130 (0.2)	273 (1.4)	< 0.001
Posttraumatic stress disorder	7 (0.0)	101 (0.5)	< 0.001
Eating disorder	26 (0.0)	141 (0.7)	< 0.001
Mean follow-up time (yr)	5.86 ± 3.00	5.53 ± 3.21

¹Urbanization level: 1 indicates the highest level of urbanization and 4 the lowest. SSRI: Selective serotonin reuptake inhibitor; NTD: New Taiwan dollars.

Table 2 Comparisons of the incidence of irritable bowel syndrome by age, gender, comorbidity and drug use

Variable	Events	PT	Rate1	HR2	(95%CI)	P value
Sex
Female	414	335363	1.23	1.00	(reference)
Male	300	233656	1.28	1.05	(0.91-1.23)	0.495
Age, yr
< 20	13	43139	0.30	1.00	(reference)
20-29	47	91408	0.51	1.62	(0.87-3.01)	0.128
30-39	93	110721	0.84	2.52	(1.40-4.55)	0.002
40-49	153	113198	1.35	3.94	(2.22-7.02)	< 0.001
50-59	133	80752	1.65	4.56	(2.54-8.17)	< 0.001
≥ 60	275	129801	2.12	5.57	(3.12-9.92)	< 0.001
Comorbidity (yes vs no)
Diabetes mellitus	113	55858	2.02	0.93	(0.74-1.17)	0.549
Hypertension	269	129073	2.08	1.06	(0.87-1.28)	0.576
Hyperlipidemia	175	84352	2.07	1.07	(0.88-1.31)	0.482
Colorectal cancer	5	1527	3.27	1.48	(0.61-3.58)	0.386
Major depressive disorder	67	30292	2.21	1.19	(0.90-1.57)	0.217
Anxiety disorder	220	96735	2.27	1.33	(1.11-1.59)	0.002
Bipolar disorder	5	2435	2.05	1.03	(0.42-2.52)	0.820
Anti-psychotics
No	630	535264	1.18	1.00	(reference)
Yes	84	33755	2.49	1.18	(0.92-1.50)	0.193
SSRIs
No	478	460307	1.04	1.00	(reference)
Yes	236	108713	2.17	1.74	(1.44-2.10)	< 0.001

¹Per 1000 person-years;

²Adjusted by age, sex, urbanization, family income, area of residence, occupation, anti-psychotics and the comorbidities listed in Table 1. IBS: Irritable bowel syndrome; SSRIs: Selective serotonin reuptake inhibitors.

Table 3 Incidence rate and hazard ratio of irritable bowel syndrome associated with selective serotonin reuptake inhibitor use in Cox regression analysis

	SSRI use (2000-2010)						aHR2	(95%CI)	P value
	No (n = 78612)			Yes (n = 19653)
	Event	Person-years	Incidence rate of IBS1	Event	Person-years	Incidence rate of IBS
Overall	478	460307	1.04	236	108713	2.17	1.74	(1.44-2.10)	< 0.001
Sex
Female	282	270195	1.04	132	65169	2.03	1.65	(1.29-2.11)	< 0.001
Male	196	190112	1.03	104	43544	2.39	1.85	(1.38-2.48)	< 0.001
Age
< 20	8	34575	0.23	5	8564	0.58	1.12	(0.23-5.41)	0.884
20-29	27	73594	0.37	20	17815	1.12	2.78	(1.36-5.70)	0.005
30-39	61	89305	0.68	32	21416	1.49	1.95	(1.13-3.34)	0.016
40-49	96	91299	1.05	57	21899	2.60	1.79	(1.19-2.69)	0.005
50-59	85	65244	1.30	48	15508	3.10	2.17	(1.40-3.36)	< 0.001
≥ 60	201	106290	1.89	74	23511	3.15	1.32	(0.97-1.79)	0.077

¹per 1000 person-years;

²aHR, adjusted by age, sex, urbanization, family income, area of residence, occupation, anti-psychotics and the comorbidities listed in Table 1. IBS: Irritable bowel syndrome; SSRI: Selective serotonin reuptake inhibitor.

Table 4 Hazard ratio of irritable bowel syndrome associated with duration of selective serotonin reuptake inhibitor exposure over one year

	aHR1	(95%CI)	P value
SSRI non-users	1.00	(reference)
SSRI exposure < 90 d	3.27	(2.61-4.08)	< 0.001
SSRI exposure 90-180 d	1.38	(1.03-1.85)	0.029
SSRI exposure 181-270 d	1.49	(1.05-2.13)	0.027
SSRI exposure ≥ 270 d	1.52	(1.07-2.15)	0.020

¹aHR, adjusted by age, sex, urbanization, family income, area of residence, occupation, anti-psychotics and the comorbidities listed in Table 1. SSRI: Selective serotonin reuptake inhibitor.

Table 5 Hazard ratio of irritable bowel syndrome among selective serotonin reuptake inhibitor and antidepressant users

	n	aHR1	(95%CI)	P value
Overall
Non-SSRIs	77327	1.00	(reference)
Non-SSRIs + other antidepressants	1285	1.33	(0.75-2.36)	0.338
SSRIs + other antidepressants	2872	1.30	(0.84-2.01)	0.235
SSRIs only	16781	1.82	(1.50-2.21)	< 0.001

¹aHR, adjusted by age, sex, urbanization, family income, area of residence, occupation, anti-psychotics and the comorbidities listed in Table 1. SSRIs: Selective serotonin reuptake inhibitors.