Improvement in social and cognitive functioning associated with paliperidone extended-release treatment in patients with schizophrenia: a 24-week, single arm, open-label study

Figures & data

Figure 1 Research flow chart.

Notes: ^aBaseline survey should be before the change of medication. If the test is terminated prematurely, endpoint visit program should be done by the termination of the test. ^bThe previously used antipsychotic drugs have been completely swapped with paliperidone ER tablets. ^cInformed consent of participants should be obtained before any research-related programs. ^dBaseline dose is the prescription dose by researchers in follow-up treatment with subjects. ^eFollow-up and endpoint dose record is the actual dose taken by patients. ^fLaboratory tests include blood and urine tests, liver function (ALT, AST, bilirubin), renal function (creatinine, blood urea nitrogen), and lipids (triglycerides and cholesterol). ^gRecord with treatment should include the name and dosage of the drug.
Abbreviations: AIMS, abnormal involuntary movement scale; ALT, alanine transaminase; AST, aspartate aminotransferase; BARS, Barnes akathisia scale; CGI-S, clinical global impression-severity; ER, extended-release; MATRICS, measurement and treatment research to improve cognition in schizophrenia; MCCB, MATRICS consensus cognitive battery; PANSS, positive and negative syndrome scale; PSP, personal and social performance; SAS, Simpson–Angus scale.

Table 1 Demographic and baseline data of full analysis set (FAS, n=90)

Items	Mean ± SD (95% CI) or n (%)
Age (years)	27.56±7.75 (18.00–45.00)
Sex, n (%)
Male	44 (48.89)
Female	46 (51.11)
Ethnicity, n (%)
Han	89 (98.89)
Marital status, n (%)
Married	17 (18.89)
Unmarried	68 (75.56)
Other	5 (5.55)
Family history, n (%)
Yes	12 (13.33)
No	78 (86.67)
Schizophrenia type, n (%)
Paranoid	60 (66.67)
Undifferentiated	27 (30.00)
Others	3 (3.33)
Duration of illness (years)	2.18±1.63 (0.00–5.53)
Duration of untreated psychosis (months)	9.80±12 (0.00–53.00)
Frequency of relapse	1.79±1.96 (0.00–10.00)
Frequency of hospitalization	1.07±1.31 (0.00–6.00)

Abbreviations: CI, confidence interval; FAS, full analysis set.

Table 2 Prestudy medications

Medication	Number of patients (%)	Dosage range (mg/day)
Risperidone	35 (38.90)	1–6
Olanzapine	18 (20.00)	2.5–30
Aripiprazole	14 (15.56)	5–30
Quetiapine	11 (12.22)	400–600
Ziprasidone	4 (4.44)	40–120
Perphenazine	3 (3.33)	4–40
Sulpiride	3 (3.33)	200–900
Amisulpride	2 (2.22)	400–800

Figure 2 Social function improvement after 24 weeks of treatment with paliperidone.

Abbreviation: PSP, personal and social performance.

Table 3 Proportion of participants exhibiting changes in PSP scores in each dimension at each visit

PSP	FASa (n=90)
	Baseline	Week 4	Week 12	Week 24
Socially useful activities, including work and study, n (%)
Absent	3 (3.33)	3 (3.33)	4 (4.44)	7 (7.78)
Mild	10 (11.11)	15 (16.67)	25 (27.78)	43 (47.78)
Manifest	28 (31.11)	50 (55.56)	49 (54.45)	33 (36.66)
Marked	34 (37.78)	20 (22.22)	11 (12.22)	6 (6.67)
Severe	15 (16.67)	2 (2.22)	1 (1.11)	1 (1.11)
Very severe	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)
P-valueb		<0.0001	<0.0001	<0.0001
Personal and social relationships, n (%)
Absent	1 (1.11)	2 (2.22)	4 (4.44)	10 (11.11)
Mild	10 (11.11)	21 (23.33)	33 (36.67)	47 (52.22)
Manifest	35 (38.90)	49 (54.45)	46 (51.11)	26 (28.90)
Marked	31 (34.44)	13 (14.44)	5 (5.56)	4 (4.44)
Severe	13 (14.44)	5 (5.56)	2 (2.22)	3 (3.33)
Very severe	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)
P-valueb		<0.0001	<0.0001	<0.0001
Self-care, n (%)
Absent	22 (24.44)	34 (37.78)	43 (47.78)	54 (60.00)
Mild	30 (33.33)	39 (43.33)	36 (40.00)	27 (30.00)
Manifest	24 (26.67)	14 (15.56)	9 (10.00)	7 (7.78)
Marked	14 (15.56)	3 (3.33)	2 (2.22)	2 (2.22)
Severe	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)
Very severe	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)
P-valueb		<0.0001	<0.0001	<0.0001
Disturbing and aggressive behaviors, n (%)
Absent	45 (50.00)	58 (64.44)	69 (76.67)	71 (78.89)
Mild	27 (30.00)	24 (26.67)	12 (13.33)	10 (11.11)
Manifest	8 (8.88)	7 (7.78)	8 (8.89)	8 (8.89)
Marked	5 (5.56)	1 (1.11)	1 (1.11)	1 (1.11)
Severe	5 (5.56)	0 (0.00)	0 (0.00)	0 (0.00)
Very severe	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)
P-valueb		–	–	–

Notes:

a Missing data were filled by LOCF method for each visit.

b Bowker tests were used to analyze the change after treatment and calculate P-value.

Abbreviations: FAS, full analysis set; LOCF, last observation carried forward; PSP, personal and social performance.

Figure 3 Neurocognitive improvements after 24 weeks of treatment with paliperidone (t score).

Note: *Compared to baseline, P<0.001, paired t-test or signed-rank test.

Table 4 Improvements in neurocognitive test scores after 24 weeks of treatment with paliperidone (raw scores)

Subtests	Baseline		Endpoint		Z/t	P-value	Cohen’s d
	x ± SD	95% CI	x ± SD	95% CI
Trail making test: part A	48.11±23.48	42.5–53.63	40.24±17.67	36.08–44.39	−640.00	<0.0001	0.38
Brief assessment of cognition in schizophrenia: symbol coding	44.88±10.82	42.33–47.42	46.58±11.37	43.91–49.26	225.00	0.1610	0.15
Hopkins verbal learning test-revised	22.32±6.36	20.82–23.81	24.69±5.52	23.40–25.99	4.69	<0.0001	0.40
Wechsler memory scale-third edition: spatial span	14.79±3.30	14.02–15.57	15.88±3.56	15.04–16.71	445.00	0.0006	0.32
Neuropsychological assessment battery: mazes	13.08±6.51	11.55–14.61	14.89±6.31	13.41–16.37	2.81	0.0063	0.28
Brief visuospatial memory test-revised	22.47±7.76	20.65–24.30	25.63±7.31	23.91–27.34	4.55	,0.0001	0.42
Category fluency test: animal naming (fluency)	17.13±5.67	15.79–18.46	17.64±5.32	16.39–18.89	1.05	0.2972	0.09
Mayer–Salovey–Car emotional intelligence test: managing emotions	78.09±8.06	76.20–79.99	78.19±9.18	75.98–80.39	0.21	0.8366	0.01
Continuous performance test-identical pairs	2.07±0.78	1.88–2.25	2.20±0.70	2.04–2.37	2.19	0.0316	0.18

Abbreviations: CI, confidence interval; SD, standard deviation.

Figure 4 Changes in PANSS total score after treatment with paliperidone.

Note: *Compared to baseline, P<0.001 since week 4, paired t-test or signed-rank test.
Abbreviations: PANSS, positive and negative syndrome scale; SD, standard deviation.

Figure 5 Changes in CGI-S score after treatment with paliperidone.

Note: *Compared to baseline, P<0.001 since week 4, paired t-test or signed-rank test.
Abbreviations: CGI-S, clinical global impression-severity; SD, standard deviation.

Table 5 Treatment-emergent adverse events

TEAE	Patients (N=93) n (%)
Severity	58 (62.37)
NA	1 (1.08)
Mild	41 (44.09)
Moderate	30 (32.26)
Severe	3 (3.23)
TEAEs occurring in ≥ EAEs occurring
Extrapyramidal symptoms	32 (34.41)
Weight gain	13 (13.98)
Amenorrhea	7 (7.53)
Anxiety	5 (5.38)
Akathisia	3 (3.23)
Insomnia	3 (3.23)
Headache	3 (3.23)
Dysphoria	3 (3.23)
Blood prolactin abnormal	2 (2.15)
Dizziness	2 (2.15)
Inappropriate affect	2 (2.15)
Depression	2 (2.15)
Constipation	2 (2.15)
Nausea	2 (2.15)

Abbreviations: EAE, emergent adverse events; TEAE, treatment-emergent adverse events; NA, not available.