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The present study is aimed at evaluating the efficacy and safety of long-acting risperidone on early
onset schizophrenia in adolescent patients. A total of 31 adolescent patients (13 - 18 years) with
schizophrenia met the DSM-IV-TR criteria for schizophrenia and their symptoms were stable when
orally taking risperidone or olanzapine. They were admitted into a 24 week, open-label study on the
long-acting risperidone. Risperidone was administered every 2 weeks at a dose of 25, 37.5 and up to a
maximum dose of 50 mg. The Positive and Negative Syndrome Scale (PANSS), the Clinical Global
Impressions (CGI) and the Extrapyramidal symptom rating scale (ESRS) were used to assess the
improvement in the symptoms. Improvements in the symptoms of schizophrenia occurred in patients
treated with long-acting risperidone at week 6 and continued throughout the study with significant
reduction in total PANSS score at week 24 (-4.2 0.2, P < 0.01). At the same time, 51.6% of patients were
rated as clinical improvement at the end of study. Among these 31 cases, the most frequently reported
adverse events were depression (12.9%), anxiety (9.7%), headache (9.7%) and insomnia (6.4%). ESRS
scores were reduced during the treatment with long-acting risperidone. The mean decrease in serum
prolactin and body weight was 13.1 ng/ml and 4.5 kg, respectively. Intramuscular administration of
long-acting risperidone was safe and well tolerated in adolescent patients. Long-acting risperidone also
could improve the symptoms of schizophrenia in adolescent patients.
Key words: Long-acting risperidone, early onset schizophrenia, oral risperidone, olanzapine, adolescents.
INTRODUCTION
Schizophrenia with onset during childhood or
adolescence often refers to early onset schizophrenia
(Werry et al., 1991), which presents more neurodevelopmental problems and greater chronicity
(Armenteros et al., 1995), as compared with adult onset
disorder. Atypical antipsychotics have both significantly
improved positive and negative symptoms (Kumra et al.,
Ruan et al.
185
186
Characteristic
Male (%)
Age (year)
Body weight (kg)
2
BMI (kg/m )
Schizophrenia diagnosis, %(n)
Paranoid
Undifferentiated
Disorganized
Catatonic
Pre-antipsychotic treatment
Olanzapine
Risperidone (po)
(n=18)
(n=13)
38.8
46.1
16.3 2.6
15.4 3.2
52.3 12.7
47.9 13.6
27.1 8.5
25.6 6.7
77.8 (14)
5.6 (1)
11.1 (2)
5.6 (1)
Rating Scale (ESRS) (Chouinard et al., 1980) before the study and
at each visit. Results from standard clinical laboratory tests and
electrocardiography and body weight were assessed at baseline
and 6, 12, 18 and 24 weeks after long-acting risperidone treatment.
Vital signs were measured at each visit. Patients completed an
assessment for pain with a 100 mm visual analogue scale (VAS) 5
min after each injection and investigators rated injection-site pain,
redness, swelling and in duration with a categorical scale (absent,
mild, moderate, or severe) at each injection; both assessments
were performed at baseline and every 2 weeks from week 2 to 24.
Statistical analysis
Safety was assessed in all patients who received at least one
injection of long-acting risperidone and efficacy in patients who
received at least one injection and completed at least one postbaseline PANSS assessment. Descriptive statistics, including
clinical characteristics and treatment-emergent adverse events
were summarized for all treated subjects according to initial oral
antipsychotic treatment group at all time points. Changes in the vital
signs, body weight and body mass index, electrocardiography and
ESRS scores. Means were presented as means standard
deviation (SD). The variable of primary efficacy was defined as the
changes in total PANSS score from baseline to endpoint and that of
secondary efficacy as a CGI severity rating at each assessment.
The changes in the rating scale score from baseline to each visit
and endpoint were analyzed with Wilcoxon signed-rank (PANSS)
and paired t-tests (ESRS). A value of P < 0.05 was considered
statistically significant. A last-observation-carried-forward (endpoint)
analysis was performed on data from PANSS and ESRS.
RESULTS
A total of 31 adolescent patients with early onset
schizophrenia were enrolled. They completed the run-in
period on current oral antipsychotics and received at
least one injection of long-actingrisperidone. Baseline
demographics and other clinical characteristics of these
31 patients are summarized in Table 1. Patients were
predominantly female (58.1%), with a mean age of 15.9
years and 77.4% had a diagnosis of paranoid
schizophrenia. Pre-study antipsychotics in the 31 patients
76.9 (10)
7.7 (1)
15.3 (2)
0
Total
(n=31)
41.9
15.9 3.3
50.2 14.1
26.3 7.6
77.4 (24)
6.5 (2)
12.9 (4)
3.2 (1)
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187
Table 2. Mean PANSS total scores and positive and negative factor scores at baseline and mean changes
at the end of treatment with long-acting risperidone.
Variable
Pre-antipsychotic treatment
Olanzapine
Risperidone (po)
(N = 18)
(N = 13)
Total
(N = 31)
58.1 1.9
**
-4.3 0.5
57.3 1.6
-4.5 0.7**
57.8 1.8
**
-4.4 0.2
16.8 0.7
**
-1.0 0.5
17.2 0.5
**
-1.1 0.7
17.0 0.8
**
-1.0 0.7
15.2 0.5
*
-0.8 0.4
14.7 0.4
**
-0.9 0.6
15.0 0.6
*
-0.9 0.9
12.6 0.5
**
-1.1 0.6
13.7 0.4
**
-1.1 0.5
13.2 0.6
**
-1.1 0.7
5.8 0.8
*
-0.4 0.6
6.1 0.3
*
-0.4 0.5
5.9 0.6
*
-0.4 0.8
7.7 0.3
**
-1.0 0.7
5.6 0.3
**
-1.0 0.5
6.8 0.8
**
-1.0 0.6
*? Difference in least squares means. *P < 0.05 vs baseline. ** P < 0.001 vs baseline.
188
59
ol amzapi ne
58
r i sper i ndone
57
t ot al
56
55
M ean C hanges
*
*
54
**
**
**
**
**
**
53
**
52
**
51
50
49
48
basel i ne
w6
w12
w18
w24
endpoi nt
Figure 1. Mean changes in the PANSS total score from baseline to the end of treatment (LOCF).
*P < 0.05 vs baseline. **P < 0.001 vs baseline.
17. 5
ol amzapi ne
r i sper i ndone
17
t ot al
Mean Changes
16. 5
16
**
**
**
**
15. 5
**
**
**
15
14. 5
14
basel i ne
w6
w12
w18
w24
endpoi nt
Figure 2. Mean changes in the scores on positive syndrome scale of PANSS from baseline to endpoint (LOCF). *P < 0.05 vs baseline. **P <
0.001 vs baseline.
Ruan et al.
15. 5
189
ol amzapi ne
r i sper i ndone
Mean Changes
15
t ot al
14. 5
**
**
**
*
**
*
**
**
14
**
**
**
**
13. 5
13
12. 5
basel i ne
w6
w12
w18
w24
endpoi nt
Figure 3. Mean changes in the scores on negative syndrome scale of PANSS from baseline to endpoint (LOCF). * P < 0.05 vs
baseline. **P < 0.001 vs baseline.
% of patients
70
60
50
40
% of patientS
30
20
10
0
20%
40%
60%
20,
40 and
10% patients
190
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
mar ked
moder at e
ver y mi l d t o mi l d
basel i ne
w6
w12
w18
w24
endpoi nt
Figure 5. Percentage of patients whose illness were rated as very mild to mild, moderate and marked (severe?) at baseline and the end of
treatment.
Adverse event
Insomnia
Anxiety
Headache
Depression
Table 4. Mean prolactin level, body weight, BMI and ESRS score at Baseline and at the end of
treatment (LOCF) in patients with long-acting risperidone treatment.
Pre-antipsychotic treatment
Olanzapine
Risperidone (po)
(n = 18)
(n = 13)
Total (n=31)
31.3 11.3
*
42.9 13.6
87.4 15.5
**
40.2 14.8
54.8 17.7
*
41.7 16.5
54.3 12.7
**
49.2 11.5
47.9 13.6
46.2 11.5
51.6 14.1
**
47.9 11.5
BMI (kg/m )
Baseline
end of treatment
27.1 8.5
*
25.7 8.1
25.6 6.7
25.1 7.4
26.5 7.6
*
25.4 8.7
ESRS score
Baseline
end of treatment
0.39 0.13
0.41 0.16
0.48 0.13
*
0.40 0.15
0.43 0.17
0.41 0.21
Variable
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