Effectiveness of amisulpride in Chinese patients with predominantly negative symptoms of schizophrenia: a subanalysis of the ESCAPE study

Figures & data

Table 1 Summary of baseline patient characteristics and medication use

Characteristics, n (%)	Patients with predominantly negative symptoms (n=26)
Male	15 (57.7)
Mean BMI, kg/m^2 (SD)	23.5 (4.2)
Type of schizophrenia defined by ICD-10
Paranoid	4 (15.4)
Hebephrenic	0 (0.0)
Catatonic	1 (3.8)
Undifferentiated	16 (61.5)
Residual	2 (7.7)
Simple	3 (11.5)
Received previous treatment for schizophrenia	23 (88.5)
Mean starting dose of amisulpride, mg/day (SD)	253.8 (94.8)
Mean dose of amisulpride over 2-week study duration, mg/day (SD)	489.2 (150.6)
Mean dose of amisulpride over 4-week study duration, mg/day (SD)	574.2 (180.3)
Mean dose of amisulpride over 8-week study duration, mg/day (SD)	623.9 (190.4)
Use of concomitant medication
Anxiety and agitation (benzodiazepines)	3 (11.5)
Extrapyramidal disorder (trihexyphenidyl, promethazine and diphenhydramine)	6 (23.1)
Insomnia (zolpidem, zopiclone and zaleplon)	0 (0.0)

Abbreviations: BMI, body mass index; ICD, International Classification of Diseases.

Table 2 Patient level data grouped by those who achieved ≥50% decrease in PANSS negative score from baseline to week 8 and those who did not

	Age (years)	Sex	Type of schizophrenia	Starting dose of amisulpride (mg/day)	Average daily dose week 2 (mg)	Average daily dose week 4 (mg)	Average daily dose week 8 (mg)	≥20% decrease in PANSS negative score from baseline to week 2	Baseline PANSS negative score	Decrease in PANSS negative score from baseline to week 2	Decrease in PANSS negative score from baseline to week 4	Decrease in PANSS negative score from baseline to week 8
Patients who achieved a ≥50% decrease in PANSS negative score from baseline to week 8 (n=9)
1	24	Male	Undifferentiated	200	543	571	586	Y	23	16	12	14
2	22	Female	Undifferentiated	200	429	514	557	Y	22	4	9	15
3	26	Female	Undifferentiated	200	414	507	554	Y	26	6	13	16
4	43	Female	Residual	400	629	779	600	N	42	2	16	23
5	49	Female	Undifferentiated	200	571	686	742	Y	28	5	8	12
6	28	Male	Undifferentiated	200	323	289	295	Y	37	8	13	20
7	22	Female	Simple	200	229	214	207	Y	27	10	11	15
8	29	Male	Undifferentiated	200	338	343	322	N	37	2	13	20
9	42	Male	Residual	200	457	529	468	N	35	4	16	20
Patients who did not achieve a ≥50% decrease in PANSS negative score from baseline to week 8 (n=17)
10	28	Male	Undifferentiated	200	682	793	807	Y	28	6	6	6
11	22	Male	Paranoid	200	743	771	786	N	24	3	4	4
12	23	Male	Undifferentiated	100	200	407	604	N	36	0	5	11
13	32	Male	Undifferentiated	200	323	264	407	N	25	−6	−1	1
14	23	Male	Simple	200	–	–	–	N	25	−1	−1	−1
15	24	Male	Undifferentiated	200	627	707	754	Y	39	7	8	14
16	31	Female	Paranoid	400	400	400	600	N	38	3	6	15
17	25	Male	Simple	200	292	350	346	Y	27	4	4	5
18	21	Female	Catatonic	300	377	604	617	N	46	3	5	5
19	34	Male	Undifferentiated	200	586	693	778	N	23	1	4	2
20	48	Female	Undifferentiated	400	543	671	746	N	40	5	9	15
21	32	Female	Paranoid	400	600	700	850	N	27	2	4	6
22	33	Female	Undifferentiated	400	643	721	761	N	37	0	1	10
23	31	Male	Paranoid	400	640	714	757	N	40	3	14	15
24	20	Male	Undifferentiated	400	646	729	764	N	38	5	12	14
25	34	Female	Undifferentiated	200	500	750	875	N	35	1	7	10
26	28	Male	Undifferentiated	200	494	650	814	N	25	0	0	6

Abbreviations: N, no; PANSS, Positive and Negative Syndrome Scale; Y, yes.

Table 3 Summary of treatment effectiveness in patients with predominantly negative symptoms of schizophrenia and corresponding average week 8 dose of amisulpride

Variablesa	Patients with predominantly negative symptoms (n=26)
≥50% decrease in PANSS negative score from baseline to week 8, n (%)b	9 (34.6)
Mean week 8 dose of amisulpride, mg/day (SD)
Patients achieving ≥50% decrease in PANSS negative score from baseline to week 8	481.2 (173.0)
Patients not achieving ≥50% decrease in PANSS negative score from baseline to week 8	704.1 (151.5)
≥20% decrease in PANSS negative score from baseline to week 2, n (%)	9 (34.6)
Mean week 2 dose of amisulpride, mg/day (SD)
Patients achieving ≥20% decrease in PANSS negative score from baseline to week 2	456.7 (158.0)
Patients not achieving ≥20% decrease in PANSS negative score from baseline to week 2	507.4 (148.3)
≥50% decrease in PANSS total score from baseline to week 8, n (%)c	13 (50.0)
≥20% decrease in PANSS total score from baseline to week 2, n (%)	13 (50.0)
Percent reduction in PANSS scores from baseline to week 8, mean (SD)
PANSS total score	50.3d (23.3)
PANSS positive score	56.6d (53.3)
PANSS negative score	45.2d (26.4)
Change in mean CGI-S score from baseline to week 8, change (SD) (baseline – week 8, %)	−1.9 (1.1) (5.2 to 3.3; 36.5)d
Change in individual PANSS negative symptom items from baseline to week 8, mean (SD)
Blunted affect	−1.9 (1.26)
Emotional withdrawal	−1.8 (1.23)
Poor rapport	−1.5 (1.17)
Passive/apathetic social withdrawal	−2.0 (1.15)
Difficulty in abstract thinking	−1.4 (1.47)
Lack of spontaneity and conversation flow	−1.7 (1.16)
Stereotyped thinking	−1.0 (1.34)

Notes:

a Last observation carried forward was used for patients with missing data;

b Including six patients who achieved a ≥20% decrease in PANSS negative score from baseline to week 2 and three who did not;

c Including nine patients who achieved a ≥20% decrease in PANSS total score from baseline to week 2, and four patients who did not;

d P<0.001 for Student’s t-test.

Abbreviations: CGI-S, Global Clinical Impression Severity Scale; PANSS, Positive and Negative Syndrome Scale.

Figure 1 Summary of changes in PANSS total score, and positive and negative symptom scores over 8 weeks of amisulpride treatment in patients with predominantly negative symptoms of schizophrenia.

Notes: Error bars represent SD. Last observation carried forward was used for patients with missing data.
Abbreviation: PANSS, Positive and Negative Syndrome Scale.

Figure 2 A comparison of the mean decrease in PANSS negative and total score and CGI-S score from baseline to weeks 2, 4 and 8 in patients with predominantly negative symptoms of schizophrenia.

Note: Last observation carried forward was used for patients with missing data.
Abbreviations: CGI-S, Global Clinical Impression Severity Scale; PANSS, Positive and Negative Syndrome Scale.

Figure 3 Change in individual items of the PANSS negative symptom score from baseline to weeks 2, 4 and 8 in patients with predominantly negative symptoms of schizophrenia.

Notes: Error bars represent SD. Last observation carried forward was used for patients with missing data.
Abbreviation: PANSS, Positive and Negative Syndrome Scale.

Table 4 Summary of safety data

Variables, n (%)	Patients with predominantly negative symptoms (n=26)
≥1 treatment-related AE	11 (42.3)
Investigations	5 (19.2)
Blood prolactin increase (>25 ng/mL)a	4 (15.4)
Electrocardiogram QT prolonged	1 (3.8)
Weight increased	1 (3.8)
Nervous system disorders	5 (19.2)
Extrapyramidal disorder	4 (15.4)
Somnolence	1 (3.8)
Tremor	1 (3.8)
Cardiac disorders	2 (7.7)
Gastrointestinal disorders	1 (3.8)
Nausea	1 (3.8)
General disorders and administration site conditions	1 (3.8)
Feeling jittery	1 (3.8)
Weight gain (>7% increase from baseline)
Week 2	0 (0.0)
Week 4	0 (0.0)
Week 8	1 (3.8)

Note:

a Blood prolactin increase with clinical symptoms.

Abbreviation: AE, adverse events.