Objectives: To evaluate the treatment result of clozapine in schizophrenic patients respond poorly to classic neuroleptiques. Subjects and methods: A prospective, cross-sectional, caseby-case analysis on 61 schizophrenic inpatients who responded poorly to classic haloperidol, aged 16 to 55 years and received treatment at National Psychiatric Hospital No 1 between 2014 and 2017.
Trang 1THE ASSOCIATION BETWEEN DOSE OF CLOZAPINE AND PANSS SCALE IN PATIENTS WITH SCHIZOPHRENIA
POORLY RESPONSIVE TO CLASSIC NEUROLEPTIQUES
Phung Thanh Hai*; Bui Quang Huy**; Cao Tien Duc**
SUMMARY
Objectives: To evaluate the treatment result of clozapine in schizophrenic patients respond poorly to classic neuroleptiques Subjects and methods: A prospective, cross-sectional, case-by-case analysis on 61 schizophrenic inpatients who responded poorly to classic haloperidol, aged 16 to 55 years and received treatment at National Psychiatric Hospital No 1 between 2014 and 2017 The data were processed by medical statistics using program SPSS Version 17 Result: PANSS scores were significantly different before and after clozapine treatment Scores
of P-PANSS, N-PANSS, G-PANSS and S-PANSS at three surveys were different with statistical significance Haloperidol and clozapine had a positive correlation but very weak between dose and plasma levels Conclusion: PANSS scores in patients with schizophrenia, who responded poorly to haloperidol, were significantly different before and after clozapine treatment
* Keywords: Schizophrenia; Classic neuroleptiques; Clozapine; PANSS scale
INTRODUCTION
Schizophrenia is a group of severely
psychotic disorders The incidence of
schizophrenia ranged from 0.3 to 1.5% of
the population Approximately 30 - 40% of
patients with schizophrenia respond poorly
or do not respond to classic neuroleptique
Symptoms in these patients did not
improve after 4 weeks of treatment with
classic antipsychotics These patients must
be treated with clozapine
Sadock B.J (2015) argues that there is
a strong correlation between dose of
clozapine and therapeutic efficacy [4]
Therefore, dose of clozapine should be
carefully monitored so that dosages can
be adjusted to improve therapeutic efficacy
In Vietnam, there haven’t even been any studies on the association between dose
of clozapine and the results of treatment
of schizophrenic patients who respond poorly to classic antipsychotics We
aimed: To evaluate the treatment results of
clozapine in schizophrenic patients responding
poorly to classic neuroleptiques
SUBJECTS AND METHODS
The study included 61 schizophrenic inpatients, aged 16 - 55 years, who was received treatment at National Psychiatric
Hospital No 1 between 2014 and 2017
* National Psychiatric Hospital No 1
** 103 Military Hospital
Corresponding author: Phung Thanh Hai (phungthanhhai18@yahoo.com)
Date received: 11/04/2018
Date accepted: 31/08/2018
Trang 2Patients were treated for the first
4 weeks with adequate dose of
haloperidol but they improved less
than 20% of PANSS score Then, the
patients were treated with clozapine
The results were collected at the time
of three months, separated by
30 days
Use method of prospective, cross-sectional, case-by-case analysis The data were processed by medical statistics using program SPSS version 17
RESULTS
Table 1: Relationship between dose of clozapine and PANSS score
Dose of clozapine (mg/day)
(n = 61) Dose
PANSS score
Time 2 (228.69 ± 48.48)
Time 3 (228.69 ± 48.48)
Time 4 (228.69 ± 48.48)
∑ PANSS total
∑ Thought
The association between the dose of
clozapine and the PANSS scale in patients
with schizophrenia showed that the all
respondents were significantly different in
the three surveys with p < 0.001
Varuni D.S and Raveen H (2010)
studied 67 schizophrenic patients, who
were started with clozapine due to
resistance to at least two other
antipsychotics Although a minimum daily
dose of 200 mg is recommended for
clozapine, 12 patients (17.9%) were on a
daily dose of 200 mg/day while 5 were on
150 mg/day Of the sample, 43.3% were
on 225 - 400 mg/day Only 3 patients were on more than 600 mg/day
Mohammad S (2005) studied on
11 schizophrenic patients, who was received treatments with clozapine Before treatment, the total PANSS score was
235, and after treatment it decreased to
123 (p < 0.0001); t = -7.83
Our results are consistent with the above authors
Trang 3Table 2: Relationship between dose of clozapine and P-PANSS score
Dose of clozapine (mg/day)
(n = 61)
Dose
P-PANSS
Time 2 (228.69 ± 48.48)
Time 3 (228.69 ± 48.48)
Time 4 (228.69 ± 48.48)
P1 Delusions 3.11 ± 1.97 1.56 ± 0.50 1.18 ± 0.39 p < 0.001 p < 0.001 P2 Conceptual
disorganization 3.97 ± 0.89 2.46 ± 0.53 1.98 ± 0.13 p < 0.001 p < 0.001
P3 H allucinations 2.98 ± 1.87 1.52 ± 0.50 1.20 ± 0.40 p < 0.001 p < 0.001 P4 Excitement 4.20 ± 0.51 2.05 ± 0.28 1.84 ± 0.37 p < 0.001 p < 0.001 P5 Grandiosity 3.69 ± 0.50 1.75 ± 0.47 1.36 ± 0.48 p < 0.001 p < 0.001 P6 S uspiciousness 4.72 ± 0.80 2.13 ± 0.34 1.88 ± 0.32 p < 0.001 p < 0.001 P7 Hostility 4.44 ± 0.59 2.15 ± 0.40 1.98 ± 0.13 p < 0.001 p < 0.001
There was a significant difference in P-PANSS among the three surveys with p < 0.001 According to Mohammad S (2005), P-PANSS pre-treatment was 34 ± 8.81 and after 3 months treatment, this figure was 17 ± 3.76 Our results were consistent with the Mohammad S
Table 3: Relationship between dose of clozapine and N-PANSS score
Dose of clozapine (mg/day)
(n = 61) Dose
N-PANSS
Time 2 (228.69 ± 48.48)
Time 3 (228.69 ± 48.48)
Time 4 (228.69 ± 48.48)
N2 Emotional
N4 Passive/
apathetic social
withdrawal
N5 Difficulty in
N6 Lack of
spontaneity and flow
of conversation
N7 Stereotyped
The three surveys of N-PANSS were very diverse N2, N3, N5, N6 and N7 were statistically significant differences with p < 0.001 From the study by Mohammad S
Trang 4(2005), N-PANSS pre-treatment was 34.45 ± 8.8 and after 3 months treatment was 18.45 ± 5.62 Our results were consistent with the Mohammad S
Table 4: Relationship between dose of clozapine and G-PANSS
Dose of clozapine (mg/day)
(n = 61) Dose
G-PANSS
Time 2 (228.69 ± 48.48)
Time 3 (228.69 ± 48.48)
Time 4 (228.69 ± 48.48)
G1 Somatic concern 3.84 ± 0.66 3.39 ± 0.56 1.97 ± 0.36 p < 0.001 p < 0.001
G2 Anxiety 3.92 ± 0.59 3.38 ± 0.61 1.90 ± 0.30 p < 0.001 p < 0.001
G3 Guilty feelings 3.77 ± 0.50 4.31 ± 0.59 1.97 ± 0.18 p < 0.001 p < 0.001
G5 Mannerisms and
posturing 3.84 ± 0.37 2.95 ± 0.22 2.00 ± 0.00 p < 0.001 p < 0.001
G8 Uncooperativeness 4.43 ± 0.56 2.31 ± 0.50 1.98 ± 0.13 p < 0.001 p < 0.001
G9 Unusual thought
content 4.49 ± 0.50 2.34 ± 0.48 2.00 ± 0.00 p < 0.001 p < 0.001
G10 Disorientation 1.00 ± 0.00 1.00 ± 0.00 1.00 ± 0.00 p < 0.001 p < 0.001
G11 Poor attention 4.57 ± 0.49 2.47 ± 0.50 2.33 ± 0.47 p < 0.001 p < 0.001
G12 Lack of judgment
and insight 4.64 ± 0.52 2.74 ± 0.44 2.28 ± 0.45 p < 0.001 p < 0.001
G13 Disturbance of
volition 4.28 ± 0.58 2.11 ± 0.32 2.00 ± 0.00 p < 0.001 p < 0.001
G14 Poor impulse
control 4.82 ± 0.39 2.08 ± 0.28 2.03 ± 0.18 p < 0.001 p < 0.001
G15 Preoccupation 3.74 ± 0.44 2.16 ± 0.37 2.00 ± 0.00 p < 0.001 p < 0.001
G16 Active social
avoidance 4.82 ± 0.39 2.51 ± 0.54 2.25 ± 0.43 p < 0.001 p < 0.001
The relationship between the dose of clozapine and the G-PANSS showed significant differences among the 3 surveys with p < 0.001 Our results were consistent with the Mohammad S (2005), G-PANSS pre-treatment was 64.27 ± 16.1 and after 3 months treatment was 32.16 ± 11.1
Trang 5Table 5: Relationship between dose of clozapine and S-PANSS
Dose of clozapine (mg/day)
(n = 61) Dose
S-PANSS
Time 2 (228.69 ± 48.48)
Time 3 (228.69 ± 48.48)
Time 4 (228.69 ± 48.48)
S2 Exasperated when
satisfaction of
requests was delayed
For the three surveys of S-PANSS, there were significant differences with p < 0.001
Our results were consistent with the Mohammad S (2005); S-PANSS pre-treatment
was 25.45 ± 6.28 and after 3 months treatment was 12.18 ± 1.99
Table 6: Relationship between dose of clozapine and five groups PANSS score
Dose of clozapine (mg/day)
(n = 61 Dose
PANSS
Time 2 (228.69 ± 48.48)
Time 3 (228.69 ± 48.48)
Time 4 (228.69 ± 48.48)
∑ Thought
There was a clear and significant difference between dose of clozapine and five
groups PANSS in all surveys with p < 0.001 In the study by Mohammad S (2005),
PANSS score for anergia pre-treatment was 31.87 ± 5.64 and after 3 months treatment
with clozapine was 9.27 ± 2.72; thought disturbance pre-treatment was 18.72 ± 3.46
and after 3 months treatment was 9.63 ± 2.57; activation pre-treatment was 11.9 ± 3.35
and after 3 months treatment was 6 ± 1.34; paranoid bellig before treatment was 14.18 ± 3.54 and after treatment was 7.27 ± 1.27; depression before treatment was
14.63 ± 3.26 and 8.18 ± 1.83 after treatment Our results were consistent with the
Mohammad S
Trang 6Table 7: Relationship between dose and plasma level of clozapine
(mg/day)
Plasma level (ng/ml)
Correlation coefficients
(r)
Linear correlations between dose and
plasma level of haloperidol and clozapine
during each survey period showed:
- For haloperidol, there was a linear
but very weak correlation (r = 0.3757)
- The second survey of clozapine
found that the correlation coefficient was
very weak (r = 0.3144); third and fourth
survey of clozapine was found to be
unrelated (r = 0.11666 and 0.0746)
Pierre-Michel L, Christophe L, Béatrice D
(2002) studied twenty-seven men and
10 women with schizophrenia The mean
dosage of clozapine at endpoint was
486.5 mg/day for mean plasma levels of
543.8 ng/mL for clozapine There was a
significant correlation between daily dosage
of clozapine and clozapine plasma level
(p < 0.05) Our results were consistent
with the above authors
Dragan B.R, Slavica M.D.D, Vladimir J
et al (2009) conducted a prospective,
active-controlled study with 325 adult
outpatients of both genders (140 females),
with mean age of 34.8 year (range 21 - 57),
suffering from chronic schizophrenia
The patients were allocated to receive
haloperidol (105 subjects, dose range
2 - 15 mg), chlorpromazine (n = 105,
100 - 400 mg) or clozapine (n = 115,
75 - 600 mg) The statistically significant differences in all psychometric scores was found, for both schizophrenic syndrome,
in preference for clozapine Clozapine was safer and had fewer adverse effects than haloperidol and chlorpromazine Our results were consistent with the above authors
CONCLUSION
- Total PANSS scores were significantly different before and after clozapine treatment at three surveys
- Scores of P-PANSS, N-PANSS, G-PANSS and S-PANSS at three surveys were different with statistical significance (p < 0.001)
- The PANSS scores for the five groups
of impaired symptoms, mental disorders, motor impairment, paranoid and depression among the participants were statistically different with p < 0.001
- Haloperidol and clozapine had a positive but very weak correlation between dose and plasma concentration
Trang 7REFERENCES
1 Dragan B.R, Slavica M.D.D, Vladimir J
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and clopromazine in schizophrenia during
five-year period Arq Neuropsiquiatr 2009, 67
(2-A), pp.195-202
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and clozapine treatment on schizophrenia
using positive and negative syndrome scale of
schizophrenia (PANSS) and SPECT Imaging
International Journal of Medical Sciences
ISSN 1449-1907 www.medsci.org 2(2), pp.79-86
3 Pierre-Michel L, Christophe L, Béatrice D
et al Effectiveness of clozapine in
neuroleptic-resistant schizophrenia: Clinical response and plasma concentrations J Psychiatry Neurosci 2002, 27 (1), pp.30-37
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Schizophrenia Kaplan & Sadock's Sinosis of Psychiatry Behavioral Sciences/Clinical Psychiattry Eleventth edition Wolter Kluwer
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clozapine in patients with chronic schizophrenia
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