Rehospitalization Risk of Receptor-Affinity Profile in Antipsychotic Drug Treatment: A Propensity Score Matching Analysis Using a Japanese Employment-Based Health Insurance Database

Figures & data

Figure 1 Patients flowchart.

Notes:^aAsenapine, clozapine, olanzapine, quetiapine and risperidone. ^bAripiprazole, blonanserin, paliperidone and perospirone.

Abbreviations: ATC, Anatomical Therapeutic Chemical; ICD, International Classification of Disease; HA, histamine H1 receptors, adrenaline α1 receptors.

Table 1 Patient Characteristics

			Eligible Patients		Primary Objective Population (PS-matched)		Secondary Objective Population
			HA High-Affinity Drugs^a (N=2120)	HA Low-Affinity Drugs^b (N=820)	HA High-Affinity Drugs^a (N=819)	HA Low-Affinity Drugs^b (N=819)	Rehospitalization (Case) (N=429)	No Rehospitalization (Control) (N=1688)
Sex (male %)			865 (40.8%)	312 (38.0%)	305 (37.2%)	312 (38.1%)	151 (35.2%)	677 (40.1%)
Age (years, mean±SD)			38.1±13.4	35.3±13.6	35.4±13.5	35.3±13.6	36.3±13.7	37.2±13.2
Year of hospitalization n(%)		−2007	58 (2.7%)	7 (0.9%)	4 (0.5%)	7 (0.9%)	12 (2.8%)	43 (2.6%)
		2008–2010	245 (11.6%)	78 (9.5%)	79 (9.7%)	78 (9.5%)	51 (11.9%)	216 (12.8%)
		2011–2013	712 (33.6%)	258 (31.5%)	258 (31.5%)	258 (31.5%)	161 (37.5%)	643 (38.1%)
		2014-	1105 (52.1%)	477 (58.2%)	478 (58.4%)	476 (58.1%)	205 (47.8%)	786 (46.6%)
Schizoaffective disorder (%)			71 (3.3%)	24 (2.9%)	30 (3.7%)	24 (2.9%)	12 (2.8%)	58 (3.4%)
Type of hospitalization (involuntary %)			1011 (47.7%)	370 (45.1%)	374 (45.7%)	369 (45.1%)	188 (43.8%)	789 (46.7%)
Hospital category (GP %)			27 (1.3%)	11 (1.3%)	11 (1.3%)	11 (1.3%)	4 (0.9%)	24 (1.4%)
Length of stay (days)			77.2±138.8	79.4±140.1	74.7±122.3	79.5±140.1	77.3±100.3	71.1±117.3
Emergency hospitalization (%)			500 (23.6%)	199 (24.3%)	184 (22.5%)	199 (24.3%)	104 (24.2%)	384 (22.7%)
Number of antipsychotics during hospitalization (mean±SD)			1.7±1.2	1.7±1.1	1.7±1.3	1.7±1.1	1.8±1.2	1.6±1.1
Surgery during hospitalization (%)			44 (2.1%)	8 (1.0%)	14 (1.7%)	8 (1.0%)	5 (1.2%)	31 (1.8%)
Concomitant drug use (%)^c	Anxiolytic/hypnotic^d		1741 (82.1%)	682 (83.2%)	688 (84%)	681 (83.2%)	371 (86.5%)	1392 (82.5%)
	Mood stabilizer^e		656 (30.9%)	217 (26.5%)	224 (27.4%)	217 (26.5%)	156 (36.4%)	503 (29.8%)
	Antiparkinsonian drug^f		448 (21.1%)	193 (23.5%)	190 (23.2%)	192 (23.4%)	109 (25.4%)	363 (21.5%)
Diagnostic history n(%)^g	Alcohol abuse		34 (1.6%)	9 (1.1%)	10 (1.2%)	9 (1.1%)	6 (1.4%)	25 (1.5%)
	Substance use disorder		1 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	1 (0.2%)	0 (0%)
	Depression		705 (33.3%)	258 (31.5%)	254 (31%)	258 (31.5%)	159 (37.1%)	548 (32.5%)
	Diabetes		175 (8.3%)	89 (10.9%)	79 (9.6%)	88 (10.7%)	37 (8.6%)	153 (9.1%)
	Hyperlipidemia		189 (8.9%)	87 (10.6%)	80 (9.8%)	86 (10.5%)	51 (11.9%)	155 (9.2%)
	Asthma		67 (3.2%)	33 (4.0%)	39 (4.8%)	33 (4.0%)	11 (2.6%)	61 (3.6%)
	Osteoarthrosis and associated disorders		52 (2.5%)	14 (1.7%)	17 (2.1%)	14 (1.7%)	13 (3%)	32 (1.9%)

Notes: ^aAsenapine, clozapine, olanzapine, quetiapine and risperidone. ^bAripiprazole, blonanserin, paliperidone and perospirone. ^cPrescription at hospitalization. ^dDefined as N05C or N05B in ATC code. ^eLithium carbonate, sodium valproate, lamotrigine and carbamazepine. ^fDefined as N04 in ATC code. ^gDiagnosis within a month before hospitalization.

Abbreviations: ATC, Anatomical Therapeutic Chemical; HA, histamine H1 receptors, adrenaline α1 receptors; SD, standard deviation; GP, general practitioner; PS, propensity score.

Figure 2 Kaplan-Meier plot of rehospitalization (up to 12 months).

Notes:^aAsenapine, clozapine, olanzapine, quetiapine and risperidone. ^bAripiprazole, blonanserin, paliperidone and perospirone.

Abbreviations: CI, confidence interval; HA, histamine H1 receptors, adrenaline α1 receptors; HR, hazard ratio.

Figure 3 Kaplan-Meier plot of rehospitalization (Maximum assessment period).

Notes:^aAsenapine, clozapine, olanzapine, quetiapine and risperidone. ^bAripiprazole, blonanserin, paliperidone and perospirone.

Abbreviations: CI, confidence interval; HA, histamine H1 receptors, adrenaline α1 receptors; HR, hazard ratio.

Table 2 Risk Factors for Rehospitalization (Secondary Objective Analysis, N = 2117)

Variables	OR	95% CI	P-value
Medication discontinuation^a	1.095	(0.833, 1.439)	0.516
HA high-affinity drug use^a,b	1.812	(1.389, 2.365)	< 0.0001
Anxiolytic/hypnotic use^a,c	2.010	(1.535, 2.630)	< 0.0001
Mood stabilizers use^a,d	1.265	(1.006, 1.593)	0.045
Antiparkinsonian drugs use^a,e	1.076	(0.826, 1.401)	0.589
Cognitive behavioral therapy^a	1.680	(0.479, 5.895)	0.418
Sex (male vs female)	0.797	(0.635, 1.001)	0.051
Age (≥40 vs <40)^f	0.730	(0.586, 0.909)	0.005
Number of outpatient visits^a	1.001	(0.989, 1.013)	0.925

Notes: ^aPrescription within 3 months before rehospitalization (case) or within 3 months before 12th month of follow-up (control); ^bAsenapine, clozapine, olanzapine, quetiapine and risperidone. ^cDefined as N05C or N05B in ATC code. ^dLithium carbonate, sodium valproate, lamotrigine and carbamazepine. ^eDefined as N04 in ATC code. ^fAge at rehospitalization (case) or at 12th month of follow-up (control).

Abbreviations: ATC, Anatomical Therapeutic Chemical; CI, confidence interval; HA, histamine H1 receptors, adrenaline α1 receptors; OR, odds ratio.