Adherence, persistence, and inpatient utilization among adult schizophrenia patients using once-monthly versus twice-monthly long-acting atypical antipsychotics

Figures & data

Figure 1. Study design. LAI, Long-acting injection.

Figure 2. Patient selection flowchart. ICD-9, International Classification of Diseases, 9th Revision; LAI, long-acting injectable antipsychotic; OM, once monthly; TM, twice monthly.

Table 1. Patient characteristics during the baseline period.

	OM patients (n = 785)	TM patients (n = 625)	p-value^a
Index medication, n (%)
Aripiprazole	42 (5.3)
Paliperidone palmitate	743 (94.7)
Risperidone		625 (100.0)
Age at index date (years), mean ± SD [median]	39.9 ± 13.1 [39.3]	41.5 ± 13.6 [41.7]	.022*
Female, n (%)	251 (32.0)	232 (37.1)	.043*
Race, n (%)
White	404 (51.5)	291 (46.6)	.067
Black	317 (40.4)	261 (41.8)	.601
Hispanic	11 (1.4)	11 (1.8)	.589
Other	29 (3.7)	31 (5.0)	.242
Unknown	24 (3.1)	31 (5.0)	.067
State, n (%)
Florida	45 (5.7)	91 (14.6)	<.001*
Iowa	50 (6.4)	48 (7.7)	.336
Kansas	31 (4.0)	35 (5.6)	.145
Mississippi	70 (8.9)	50 (8.0)	.54
Missouri	497 (63.3)	258 (41.3)	<.001*
New Jersey	92 (11.7)	143 (22.9)	<.001*
Region characteristics, n (%)
Urban	431 (54.9)	347 (55.5)	.817
Suburban	204 (26.0)	177 (28.3)	.327
Rural	150 (19.1)	101 (16.2)	.151
Insurance eligibility, n (%)
Capitated or dual coverage	396 (50.5)	313 (50.1)	.891
Capitated	218 (27.8)	157 (25.1)	.263
Dual coverage	239 (30.5)	198 (31.7)	.619
Year of index date, n (%)
2009	21 (2.7)	92 (14.7)	<.001*
2010	170 (21.7)	178 (28.5)	.003*
2011	175 (22.3)	164 (26.2)	.085
2012	136 (17.3)	103 (16.5)	.674
2013	101 (12.9)	62 (9.9)	.086
2014	148 (18.9)	18 (2.9)	<.001*
2015	34 (4.3)	8 (1.3)	<.001*
Number of unique mental health diagnoses, mean ± SD [median]	4.8 ± 3.6 [4.0]	4.8 ± 3.5 [4.0]	.762
Number of unique AP agents received, mean ± SD [median]	1.5 ± 1.2 [1.0]	1.6 ± 1.2 [1.0]	.494
Quan-Charlson Comorbidity Index, mean ± SD [median]	0.5 ± 0.9 [0.0]	0.6 ± 1.2 [0.0]	.029*
Selected physical and mental comorbidities, n (%)
Cardiovascular disease	60 (7.6)	79 (12.6)	.002*
Depressive disorders	201 (25.6)	158 (25.3)	.889
Diabetes	104 (13.3)	103 (16.5)	.089
Schizophrenia spectrum and other psychotic disorders	546 (69.6)	453 (72.5)	.230
Substance-related and addictive disorders	248 (31.6)	216 (34.6)	.239
Oral risperidone daily equivalent^b, n (%)
Low dose (≥ 0 to <4 mg)	50 (6.4)	10 (1.6)	<.001*
Moderate dose (≥ 4 to <8 mg)	538 (68.5)	275 (44.0)	<.001*
High dose (≥ 8 mg or more)	197 (25.1)	340 (54.4)	<.001*
Healthcare resource utilization, mean ± SD [median]
Outpatient visits	0.9 ± 1.3 [0.5]	0.7 ± 1.0 [0.3]	.002*
Emergency room visits	0.1 ± 0.3 [0.0]	0.2 ± 0.3 [0.0]	.002*
Inpatient visits	0.2 ± 0.2 [0.0]	0.2 ± 0.2 [0.2]	.102
One-day mental-health institute visits	0.8 ± 1.2 [0.2]	0.6 ± 1.2 [0.0]	<.001*
Monthly all-cause pharmacy and medical costs (in 2015 USD), mean ± SD [median]	2,375 ± 3,869 [1,070]	2,499 ± 3,888 [1,212]	.496

Abbreviations. mg, milligrams; OM, once monthly; SD, standard deviation; TM, twice monthly; USD, United States dollars.

* Significant at the 5% level.

^a Pair-wise comparisons were conducted among study cohorts using the Student t-test or Wilcoxon-Mann-Whitney non-parametric test for continuous variables and the Chi-squared test for categorical variables.

^b Oral risperidone daily equivalences were calculated using the index dose, the dosing frequency, and the oral risperidone dose equivalence.

Figure 3. Comparison of persistence to index medication during the first 2 years following the index year. CI, confidence interval; HR, hazard ratio; OM, once monthly; TM, twice monthly. *Significant at the 5% level. ^aAdjusted models controlled for demographics (age, sex, race/ethnicity); region of residence (state, urban/rural area); year of the index date, number of unique mental health diagnoses recorded during the baseline period; number of unique antipsychotic agents received during the baseline period; comorbidities at baseline (diabetes, cardiovascular diseases, substance-related and addictive disorders, schizophrenia spectrum and other psychotic disorders, depressive disorders, Quan-Charlson Comorbidity Index); number of outpatient, 1-day mental-health institute, inpatient, and emergency room visits during the baseline period; total costs at baseline; Medicare eligibility; and risperidone dose equivalence on the index date. ^bOM patients vs TM patients: An HR <1 means that TM patients have a higher risk of discontinuing their index drug than OM patients.

Figure 4. Inpatient utilization during the first 12 months following the index date. *Significant at the 5% level. IRR, incidence rate ratio; OM, once monthly; SD, standard deviation; TM, twice monthly. ^aAdjusted models controlled for demographics (age, sex, race/ethnicity); region of residence (state, urban/rural area); year of the index date; number of unique mental health diagnoses recorded during the baseline period; number of unique antipsychotic agents received during the baseline period; comorbidities at baseline (diabetes, cardiovascular diseases, substance-related and addictive disorders, schizophrenia spectrum and other psychotic disorders, depressive disorders, Quan-Charlson Comorbidity Index); number of outpatient, 1-day mental-health institute, inpatient, and emergency room visits during the baseline period; total costs at baseline; Medicare eligibility; and risperidone dose equivalence on the index date. ^bIRRs, 95% CIs, and p-values were estimated using a generalized linear model (GLM) with a negative binomial distribution.

Table 2. Healthcare costs during the first 12 months following the index date.

Monthly healthcare costs during the first year after the index date (in 2015 USD), mean ± SD [median]	OM patients (n = 785)	TM patients (n = 625)	Unadjusted difference (95% CI)	p-value^a	Adjusted^b difference (95% CI)	p-value^a
Total costs	1,997 ± 2,192 [1,387]	2,199 ± 2,635 [1,475]	−202.08 (−472.71 to 20.35)	.100	−146.44 (−419.68 to 83.77)	.228
Medical costs	973 ± 1,724 [413]	1,397 ± 2,389 [552]	−424.65 (−657.99 to −217.67)	<.001*	−459.69 (−708.87 to −248.73)	<.001*
Inpatient costs	262 ± 903 [0]	524 ± 1,696 [0]	−262.48 (−438.62 to −129.48)	<.001*	−201.11 (−370.48 to −54.61)	.004*
Long-term care costs	85 ± 600 [0]	186 ± 822 [0]	−100.23 (−181.23 to −19.61)	.016*	−126.62 (−214.25 to −45.51)	.004*
Pharmacy costs	1,024 ± 1,114 [897]	802 ± 833 [603]	222.57 (123.83 to 312.74)	<.001*	313.24 (203.93 to 409.62)	<.001*

Abbreviations. CI, confidence interval; OM, once monthly; SD, standard deviation; TM, twice monthly; USD, United States dollar.

* Significant at the 5% level.

^a Cost differences, 95% CIs, and p-values were estimated using linear regressions (bootstrapped, B = 499).

^b Adjusted models controlled for demographics (age, sex, race/ethnicity); region of residence (state, urban/rural area); year of the index date; number of unique mental health diagnoses recorded during the baseline period; number of unique antipsychotic agents received during the baseline period; comorbidities at baseline (diabetes, cardiovascular diseases, substance-related and addictive disorders, schizophrenia spectrum and other psychotic disorders, depressive disorders, Quan-Charlson Comorbidity Index); number of outpatient, 1-day mental-health institute, inpatient, and emergency room visits during the baseline period; total costs at baseline; Medicare eligibility; and risperidone dose equivalence on the index date.