Association of post-stroke-initiated antidepressants with long-term outcomes in young adults with ischaemic stroke

Figures & data

Table 1. Characteristics of the PSAD non-initiators and initiators and standardized mean differences of variables in the original non-matched and matched sample.

Characteristic	Not initiated PSAD				Initiated PSAD n = 203
	Original sample^an = 660 (76.5%)		Matched sample n = 406 (66.7%)
	n (%) or median (IQR)	SMD	n (%) or median (IQR)	SMD	n (%) or median (IQR)
Sociodemographic variables
Age at IS, years	43.0 (36.0–47.0)	0.192	45.0 (38.0–47.0)	0.045	44.0 (38.5–47.0)
Male sex	428 (64.8)	0.098	248 (61.1)	0.020	122 (60.1)
Socioeconomic status		0.208		0.017
Upper white-collar worker	74 (11.2)		58 (14.3)		25 (12.3)
Lower white-collar worker	153 (23.2)		119 (29.3)		61 (30.0)
Blue collar worker	299 (45.3)		131 (32.3)		69 (34.0)
Other/unknown	134 (20.3)		98 (24.1)		48 (23.6)
Prior antidepressant use (earlier than one year)^b	41 (6.2)	0.282	39 (9.6)	0.158	30 (14.8)
Risk factors for IS
Comorbidities
Atrial fibrillation	23 (3.5)	0.002	15 (3.7)	0.013	7 (3.4)
Cardiovascular disease	61 (9.2)	0.069	40 (9.9)	0.048	23 (11.3)
Diabetes mellitus type 1	30 (4.5)	0.018	18 (4.4)	0.023	10 (4.9)
Diabetes mellitus type 2	42 (6.4)	0.019	31 (7.6)	0.069	12 (5.9)
Dyslipidaemia	388 (58.8)	0.047	244 (60.1)	0.020	124 (61.1)
Hypertension	254 (38.5)	0.109	157 (38.7)	0.105	89 (43.8)
Lifestyle factors
Current cigarette smoking	277 (42.0)	0.156	198 (48.8)	0.020	101 (49.8)
Heavy alcohol drinking	82 (12.4)	0.041	60 (14.8)	0.028	28 (13.8)
Stroke-related variables measured at hospital admission
NIHSS at admission		0.617		0.402
0–6, mild	548 (83.0)		299 (73.6)		109 (53.7)
7–14, moderate	76 (11.5)		73 (18.0)		61 (30.0)
≥15, severe	36 (5.5)		34 (8.4)		33 (16.3)
Silent infarcts	73 (11.1)	0.203	64 (15.8)	0.065	37 (18.2)
TOAST		0.097		0.057
Large-artery atherosclerosis	40 (6.1)		30 (7.4)		24 (11.8)
Cardioembolism	125 (18.9)		74 (18.2)		34 (16.7)
Small-vessel disease	100 (15.2)		68 (16.7)		22 (10.8)
Other	164 (24.8)		97 (23.9)		61 (30.0)
Undetermined causes	231 (35.0)		137 (33.7)		62 (30.5)
Disability at discharge
Limb paresis at discharge		0.789		0.535
No	518 (78.5)		271 (66.7)		92 (45.3)
Mild	84 (12.7)		77 (19.0)		36 (17.7)
Moderate–severe	58 (8.8)		58 (14.3)		75 (36.9)

PSAD: post-stroke antidepressant; IS: ischaemic stroke; NIHSS: NIH Stroke Scale; TOAST: Trial of Org 10172 in Acute Stroke Treatment; SMD: standardized mean difference.

^aIn the original sample, 25 (2.8%) patients were excluded due to missing values in socioeconomic status and limb paresis at discharge.

^bPSAD purchased earlier than a year prior to IS.

Figure 1. Estimated cumulative incidence curves in competing risks analyses for a) non-fatal vascular event vs. vascular and non-vascular mortality occurring before vascular event and b) non-fatal restroke vs. restroke and non-restroke mortality occurring before restroke in patients initiating post-stroke antidepressants (PSAD) within one year from ischaemic stroke. Eight PSAD initiators and 16 matched controls were excluded from the vascular event dataset (n = 585), and 2 initiators and 4 matched controls were excluded from the recurrent stroke dataset (n = 603), since in these cases the PSAD use started after the event of interest.

Table 2. Association between initiation of post-stroke antidepressants and mortality, any vascular event and recurrent stroke.

	Univariate	Model 1	Model 2	Model 3	Model 4
	PSADs within one year	Adjusted for age, sex and socioeconomic status	Adjusted forModel 1 + NIHSS, TOAST, silent infarct and limb paresis	Adjusted for Model 2 + smoking and heavy alcohol drinking	Adjusted for Model 3 + cardiovascular comorbidities^a
	HR (95% CI)	aHR (95% CI)	aHR (95% CI)	aHR (95% CI)	aHR (95% CI)
Mortality (n = 609)
0–5 years	0.86 (0.46–1.62)	0.83 (0.43–1.59)	0.63 (0.31–1.26)	0.66 (0.33–1.31)	0.63 (0.31–1.30)
5–10 years	0.85 (0.43–1.70)	0.79 (0.40–1.59)	0.55 (0.25–1.20)	0.58 (0.26–1.28)	0.56 (0.25–1.23)
>10 years	1.59 (0.65–3.86)	1.30 (0.55–3.08)	0.83 (0.35–1.99)	0.88 (0.36–2.10)	0.84 (0.35–2.04)
Any vascular event (n = 585)^b
0–5 years	0.90 (0.63–1.30)	0.90 (0.62–1.29)	0.92 (0.63–1.35)	0.91 (0.62–1.34)	0.88 (0.60–1.30)
5–10 years	1.91 (1.05–3.50)	1.85 (1.00–3.43)	1.87 (1.00–3.50)	1.85 (0.98–3.50)	1.76 (0.93–3.32)
>10 years	1.24 (0.43–3.61)	1.05 (0.38–2.91)	1.06 (0.36–3.08)	1.00 (0.34–2.91)	1.04 (0.35–3.06)
Recurrent ischaemic or haemorrhagic stroke (n = 603)^b
0–5 years	1.17 (0.71–1.94)	1.19 (0.72–1.96)	1.22 (0.72–2.09)	1.19 (0.69–2.05)	1.27 (0.74–2.20)
5–10 years	2.99 (1.34–6.65)	2.93 (1.29–6.65)	2.95 (1.29–6.74)	2.91(1.26–6.68)	3.07 (1.32–7.12)
>10 years	0.99 (0.25–3.93)	0.92 (0.24–3.45)	0.92 (0.23–3.65)	0.90 (0.22–3.61)	1.00 (0.25–4.02)

PSAD: post-stroke antidepressant; HR: hazard ratio; aHR: adjusted hazard ratio; CI: confidence interval; NIHSS: NIH Stroke Scale; TOAST: Trial of Org 10172 in Acute Stroke Treatment.

^aIncluding variables atrial fibrillation, hypertension, dyslipidaemia, cardiovascular disease and diabetes mellitus type 1 and type 2.

^bEight PSAD initiators and 16 matched controls were excluded from the vascular event dataset (n = 585), and 2 initiators and 4 matched controls were excluded from the recurrent stroke dataset (n = 603), since in these cases the PSAD was initiated after the event of interest.

Data availability statement

We have documented the data, methods, and materials used to conduct the research in this report. The individual patient data are not publicly available due to legal restrictions. The syntax code for study analyses in R software [26] is available from the corresponding author, J.B., upon reasonable request.