Prevalence and Determinants of Long-Term Utilization of Antidepressant Drugs: A Retrospective Cohort Study

Figures & data

Figure 1 Synopsis of cohort selection and pattern distribution.

Table 1 Demographic Characteristics of Selected Cohort

Characteristics	Full Cohort N=18,307	Chronic Use N=1819	Non-Chronic Use N=16,488	P value
Gender				0.65
Male	6065 (33.13%)	594 (32.66%)	5471 (33.26%)
Female	12,242 (66.87%)	1225 (67.34%)	11,017 (66.98%)
Age [mean (SD)]	58.46 (18.24)	60.40 (17.52)	58.24 (18.30)	<0.001
Age class				<0.001
0–17	93 (0.51%)	10 (0.55%)	83 (0.50%)
18–39	2979 (16.27%)	230 (12.64%)	2749 (16.71%)
40–59	6432 (35.13%)	597 (32.82%)	5835 (35.48%)
60–79	6096 (33.30%)	704 (38.70%)	5392 (32.78%)
80+	2707 (14.79%)	278 (15.28%)	2429 (14.77%)
Living area				<0.001
Urban	8159 (44.57%)	820 (45.08%)	7339 (44.62%)
Rural	6669 (36.43%)	729 (40.08%)	5940 (36.11%)
Missing	3479 (19.00%)	270 (14.84%)	13,279 (19.46%)
First prescriber				0.85
GP	15,226 (83.17%)	1533 (84.28%)	13,693 (83.05%)
Specialist	2743 (14.98%)	280 (15.39%)	2463 (14.94%)
Missing	338 (1.85%)	6 (0.33%)	332 (02.01%)
Initial antidepressant drug				<0.001
Sertraline	4798 (26.21%)	671 (36.89%)	4127 (25.09%)
Paroxetine	2951 (16.21%)	273 (15.01%)	2678 (16.28%)
Citalopram	2535 (13.85%)	244 (13.41%)	2291 (13.93%)
Trazodone	2061 (11.26%)	60 (3.30%)	2001 (12.17%)
Escitalopram	1512 (8.26%)	186 (10.23%)	1326 (8.06%)
Amitriptyline	1390 (7.59%)	25 (1.37%)	1365 (8.30%)
Venlafaxine	894 (4.88%)	105 (5.77%)	789 (4.80%)
Duloxetine	675 (3.69%)	79 (4.39%)	596 (3.62%)
Fluoxetine	496 (2.71%)	46 (2.53%)	450 (2.74%)
Mirtazapine	336 (1.84%)	38 (2.09%)	298 (1.81%)
Other	317 (1.73%)	18 (0.99%)	299 (1.82%)
Polytherapy	342 (1.87%)	74 (4.07%)	268 (1.63%)
Polypharmacy				<0.001
Yes	5411 (29.56%)	394 (21.66%)	5017 (30.50%)
No	12,896 (70.44%)	1425 (78.34%)	11,471 (69.74%)

Notes: Chronic use: at least 180 Defined Daily Dose (DDD) of antidepressant drug claimed in every year of follow-up. P values: all p-values but for age [mean (SD)], which was performed with independent Student t tests, were obtained by using chi square tests. Specialist: hospital or mental health center physician. Polytherapy: a combination of more than one antidepressant drugs as the initial treatment. Polypharmacy: 5 or more drugs claimed concomitantly.

Abbreviations: SD, standard deviation; GP, general practitioner.

Figure 2 Description of the first 10 prescribed concomitant drugs classes (at ATC II level) among chronic and non-chronic users during the 3-year follow-up.

Table 2 Logistic Regression Analysis of Factor Associated with Chronic Use of Antidepressant Drugs Among Men and Women Separately

Men
Characteristics	Univariate Regression			Multivariate Regression
	OR	95% CI	P value	OR	95% CI	P value
Age – Urban Area		–			–
0–17	2.16	0.48–7.08	0.25	2.02	0.44–6.84	0.30
18–39	1	-	-	1	-	-
40–59	0.84	0.58–1.22	0.34	0.76	0.52–1.11	0.15
60–79	1.13	0.79–1.63	0.51	0.88	0.60–1.30	0.52
80+	0.82	0.49–1.34	0.44	0.69	0.40–1.16	0.17
Age – Rural Area
0–17	3.74	0.80–13.07	0.05	4.60	0.95–17.26	0.03
18–39	1	-	-	1	-
40–59	1.21	0.78–1.93	0.41	1.11	0.71–1.79	0.65
60–79	1.77	1.15–2.80	0.01	1.43	0.92–2.30	0.12
80+	1.95	1.14–3.36	0.02	1.91	1.08–3.38	0.03
First Antidepressant Prescriber
GP	1	-	-	1	-	-
Specialist	1.04	0.83–1.29	0.74	2.30	1.34–3.80	<0.01
Antidepressant Drug
Sertraline	1	-	-	1	-	-
Paroxetine	0.62	0.48–0.79	<0.01	0.58	0.44–0.77	<0.01
Citalopram	0.55	0.42–0.72	<0.01	0.62	0.45–0.83	<0.01
Trazodone	0.15	0.09–0.23	<0.01	0.14	0.08–0.23	<0.01
Escitalopram	0.67	0.48–0.92	0.02	0.72	0.51–1.01	0.06
Amitriptyline	0.08	0.03–0.18	<0.01	0.09	0.03–0.19	<0.01
Venlafaxine	0.63	0.41–0.92	0.02	0.48	0.27–0.80	0.01
Duloxetine	0.49	0.29–0.78	<0.01	0.39	0.22–0.65	<0.01
Fluoxetine	0.58	0.30–1.03	0.08	0.66	0.32–1.20	0.20
Mirtazapine	0.84	0.48–1.39	0.53	0.84	0.41–1.56	0.61
Other	0.44	0.21–0.81	0.02	0.42	0.18–0.83	0.02
Polytherapy	1.47	0.89–2.34	0.11	1.34	0.66–2.55	0.39
Polypharmacy
Non	1	-	-	1	-	-
Yes	1.63	1.34–1.98	<0.01	1.64	1.28–2.10	<0.01
Women
Characteristics	Univariate Regression			Multivariate Regression
	OR	95% CI	P value	OR	95% CI	P value
Age – Urban Area
0–17	0.68	0.04–3.41	0.71	0.70	0.04–3.53	0.73
18–39	1	-	-	1	-	-
40–59	1.10	0.82–1.49	0.54	1.07	0.80–1.47	0.64
60–79	1.51	1.14–2.03	0.01	1.39	1.03–1.89	0.03
80+	1.55	1.13–2.16	0.01	1.56	1.11–2.20	0.01
Age – Rural Area
0–17	1.45	0.23–5.13	0.63	1.74	0.27–6.36	0.47
18–39	1	-	-	1	-
40–59	1.71	1.22–2.45	<0.01	1.63	1.16–2.35	0.01
60-79	2.51	1.80–3.58	<0.01	2.26	1.60–3.24	<0.01
80+	3.00	2.07–4.41	<0.01	3.22	2.18–4.28	<0.01
First Antidepressant Prescriber
GP	1	-	-	1	-
Specialist	1.00	0.85–1.18	0.97	3.45	2.33–5.03	<0.01
Antidepressant Drug
Sertraline	1	-	-	1	-	-
Paroxetine	0.63	0.52–0.76	<0.01	0.73	0.60–0.89	<0.01
Citalopram	0.71	0.59–0.86	<0.01	0.77	0.62–0.94	0.01
Trazodone	0.21	0.15–0.28	<0.01	0.19	0.13–0.27	<0.01
Escitalopram	0.96	0.78–1.18	0.73	1.07	0.86–1.33	0.54
Amitriptyline	0.13	0.08–0.19	<0.01	0.14	0.08–0.22	<0.01
Venlafaxine	0.93	0.71–1.21	0.61	0.80	0.56–0.12	0.21
Duloxetine	1.02	0.76–1.35	0.89	1.14	0.84–1.54	0.39
Fluoxetine	0.65	0.44–0.93	0.02	0.69	0.45–1.03	0.08
Mirtazapine	0.73	0.45–1.14	0.19	0.84	0.46–1.41	0.53
Other	0.30	0.13–0.58	<0.01	0.19	0.06–0.46	<0.01
Polytherapy	1.82	1.30–2.51	<0.01	2.21	1.39–3.44	<0.01
Polypharmacy
Non	1	-	-	1	-	-
Yes	1.56	1.35–1.81	<0.01	1.21	1.01–1.45	0.04

Notes: Specialist: hospital or mental health center physician; Polytherapy: a combination of more than one antidepressant drugs as the initial treatment. Polypharmacy: 5 or more drugs claimed concomitantly.

Abbreviations: OR, odds ratio; 95% CI, 95% Confidence Interval; GP, general practitioner.

Table 3 Logistic Regression Analysis of Factor Associated with Long Term Use of Antidepressants Among Men and Women Separately

Men
Characteristics	Univariate Regression			Multivariate Regression
	OR	95% CI	P value	OR	95% CI	P value
Age
0–17	1.95	0.98–3.78	0.47	2.22	0.98–4.82	0.05
18–39	1	-	-	1	-	-
40-–59	1.04	0.88–1.22	0.66	1.00	0.83–1.22	0.97
60–79	1.33	1.13–1.57	<0.01	1.31	1.07–1.61	0.01
80+	1.26	1.02–1.55	0.03	1.60	1.23–2.07	<0.01
Living Area
Urban	1	-	-	1	-
Rural	0.92	0.82–1.05	0.21	0.92	0.81–1.05	0.22
First Antidepressant Prescriber
GP	1	-	-	1	-	-
Specialist	1.06	0.91–1.22	0.47	2.69	1.77–4.11	<0.01
Antidepressant Drug – No Polypharmacy
Sertraline	1	-	-	1	-	-
Paroxetine	1.05	0.77–1.44	0.74	1.33	0.93–1.92	0.12
Citalopram	0.99	0.71–1.36	0.94	1.03	0.69–1.53	0.88
Trazodone	0.60	0.37–0.95	0.03	0.59	0.31–1.08	0.10
Escitalopram	1.19	0.81–1.73	0.36	1.34	0.88–2.04	0.17
Amitriptyline	0.36	0.18–0.65	<0.01	0.38	0.18–0.74	0.01
Venlafaxine	0.89	0.57–1.38	0.62	1.13	0.63–1.96	0.67
Duloxetine	0.63	0.29–1.23	0.20	0.66	0.29–1.37	0.29
Fluoxetine	0.95	0.47–1.79	0.87	1.17	0.54–2.38	0.68
Mirtazapine	0.91	0.43–1.79	0.80	0.87	0.31–2.13	0.78
Other	1.49	0.80–2.69	0.19	1.25	0.57–2.56	0.56
Polytherapy	0.59	0.20–1.45	0.29	0.61	0.09–2.42	0.53
Antidepressant Drug - Polypharmacy
Sertraline	1	-	-	1	-	-
Paroxetine	0.77	0.62–0.95	0.01	0.77	0.61–0.96	0.02
Citalopram	0.75	0.59–0.94	0.01	0.73	0.56–0.93	0.01
Trazodone	0.70	0.57–0.87	<0.01	0.77	0.60–0.97	0.03
Escitalopram	0.82	0.62–1.08	0.16	0.85	0.63–1.14	0.28
Amitriptyline	0.39	0.27–0.55	<0.01	0.43	0.30–0.61	<0.01
Venlafaxine	0.71	0.50–1.01	0.06	0.77	0.50–1.16	0.21
Duloxetine	0.46	0.31–0.66	<0.01	0.42	0.27–0.62	<0.01
Fluoxetine	0.68	0.40–1.13	0.15	0.75	0.42–1.28	0.30
Mirtazapine	1.23	0.78–1.92	0.37	1.38	0.78–2.41	0.26
Other	0.54	0.31–0.88	0.02	0.54	0.30–0.94	0.04
Polytherapy	1.85	1.18–2.92	0.01	1.56	0.83–2.94	0.16
Women
Characteristics	Univariate Regression			Multivariate Regression
	OR	95% CI	P value	OR	95% CI	P value
Age
0–17	1.30	0.69–2.32	0.39	2.45	1.23–4.74	0.01
18–39	1	-	-	1	-	-
40–59	1.45	1.28–1.65	<0.01	1.30	1.12–1.49	<0.01
60–79	1.76	1.55–2.00	<0.01	1.64	1.42–1.90	<0.01
80+	1.89	1.64–2.19	<0.01	2.25	1.90–2.67	<0.01
Living Area
Urban	1	-	-	1	-	-
Rural	0.94	0.87–1.03	0.19	0.96	0.88–1.05	0.36
First Antidepressant Prescriber
GP	1	-	-	1	-	-
Specialist	0.79	0.71–0.89	<0.01	2.38	1.70–3.33	<0.01
Antidepressant Drug – No Polypharmacy
Sertraline	1	-	-	1	-	-
Paroxetine	1.16	0.90–1.50	0.25	1.31	0.98–1.75	0.07
Citalopram	1.34	1.03–1.73	0.03	1.42	1.05–1.92	0.02
Trazodone	0.79	0.54–1.12	0.20	0.82	0.52–1.27	0.38
Escitalopram	1.60	1.19–2.15	<0.01	1.66	1.20–2.30	<0.01
Amitriptyline	0.40	0.25–0.62	<0.01	0.40	0.23–0.66	<0.01
Venlafaxine	1.40	0.92–1.99	0.06	0.96	0.57–1.58	0.89
Duloxetine	1.80	1.10–2.88	0.02	2.14	1.26–3.59	<0.01
Fluoxetine	0.59	0.33–0.98	0.05	0.50	0.26–0.90	0.03
Mirtazapine	1.01	0.55–1.76	0.98	1.17	0.50–2.48	0.70
Other	0.95	0.49–1.75	0.88	0.65	0.26–1.43	0.32
Polytherapy	1.53	0.86–2.62	0.13	2.27	0.75–6.45	0.13
Antidepressant Drug - Polypharmacy
Sertraline	1	-	-	1	-	-
Paroxetine	0.78	0.68–0.90	<0.01	0.84	0.72–0.98	0.02
Citalopram	0.80	0.69–0.92	<0.01	0.81	0.69–0.95	0.01
Trazodone	0.80	0.69–0.94	0.01	0.81	0.68–0.96	0.01
Escitalopram	1.09	0.92–1.29	0.34	1.15	0.96–1.37	0.13
Amitriptyline	0.45	0.37–0.55	<0.01	0.48	0.39–0.58	<0.01
Venlafaxine	0.86	0.68–1.08	0.20	0.77	0.58–1.01	0.06
Duloxetine	0.90	0.71–1.14	0.38	0.98	0.76–1.26	0.88
Fluoxetine	0.81	0.61–1.07	0.14	0.83	0.61–1.13	0.24
Mirtazapine	0.76	0.52–1.11	0.17	0.70	0.44–1.07	0.11
Other	0.88	0.59–1.30	0.53	0.80	0.51–1.23	0.32
Polytherapy	1.45	1.05–1.99	0.02	1.64	1.07–2.54	0.02

Notes: Specialist: hospital or mental health center physician; Polytherapy: a combination of more than one antidepressant drugs as the initial treatment. Polypharmacy: 5 or more drugs claimed concomitantly.

Abbreviations: OR, odds ratio; 95% CI, 95% Confidence Interval; GP, general practitioner.