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P-4-48 Clinical efficacy of clozapine in treatment-refractory schizophrenic patients
342
P-4 Antipsychotics." basic and clinical studies
were admitted to the inpatient serwce and withdrawn from all neuroleptlcs (except occasional doses of Iorazepam if needed for behavioral control) for 7-14 days. Ciozapine was started gradually on a once daily schedule: the dose was titrated as tolerated to 800 mg/day. The monoamine metabolites homovanillic acid (HVA). 5-hydroxy-indoleacetic acid (6-HIAA), and serotonin (5-HT) were measured in plasma before treatment and 2 weeks, 4 weeks, 8 weeks, 12 weeks during treatment. The plasma samples were aliquoted and frozen at - 7 0 ° C until assayed for HVA, 5-HIAA, 5-HT by high-performance liquid chromatography with electrochemical detection. Psychopathology was assessed with Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS) before and during Clozapine treatment. The mean (SD} age of the patients was 27.88 (7.38) years and the age of onset was 20.38 4- 4.90 years. Mean daily clozapine dosage were: at 4 weeks, 276,56 5 : 1 0 1 . 4 3 mg; at 8 weeks, 532.81 4- 98.86 mg; at 12 weeks, 584.38 4- 97.23 mg. During Clozapine treatment only small changes between baseline and following 2 weeks. 4 weeks 8 weeks 12 weeks HVA. 5-HIAA and 5-HT were found. However the change in serotonin index (6-HIAA/5-HT) from baseline to 4 weeks was statistically significant During treatment HVA 5-H IAA and 5-HT were not associated with psychopathology. These results suggest that Clozapine has been found to have relatively weak dopaminergic blockade and stronger serotonergic antagonism
more for poor social relations, can get worse progressively resulting in social with drawl and frequent hospitalizations. Many studies support the evidence that schizophrenic subjects receive a benefit from an integrated treatment with antipsychotic drugs and psychosocial rehabilitation. Better outcomes both in the spheres of clinical symptoms and social performance have been observed from the authors, using BPRS, SAPS, SANS and WHO/DAS in a group of chronic schizophrenics treated with clozapine. For the patients, with a history of several failures, it was possible either to plan and to put into practice psychosocial recovery, e.g. attending a residential therapeutic rehabilitation center, after a treatment with an average dose of 450 mg clozapine from 6 up to 18 months.
References
Poor response to neuroleptics is usually considered as a characteristic feature of negative symptoms of schizophrenia. Clozapine offers particular benefits for treatment-resistant schizophrenic patients in spite of the increased hematologic risk which restricts the use of clozapine to selected patients. Many studies concluded in its potent antipsychotic activity on positive symptoms of schizophrenia. The question whether negative symptoms of schizophrenia are also improved, concomitantly or independently of improvement in positive symptoms or of decrease in extrapyramidal side effects and/or depressive symptoms, remains unanswered. The authors prospectively followed up for 30 months. 13 DSM-IV resistant schizophrenics. Positive and negative symptoms were assessed by means of 1 8 item Brief Psychiatric Rating Scale (BPRS)(total and subscales: positive, cognitive, anergia and depressive mood), Positive and Negative Syndrome Scale (PANSS) positive as well as negative subscales, and Extrapyramidal Symptom Rating Scale (ESRS) prior to beginning on clozapine, at days 15. 30, 60 and 90, and further every 3 months. Friedman's test, Wilcoxon's test and Spearman's rank correlation coefficient were used to explore psychiatric ratings. Significant improvements, were noted in all psychiatric scales.
Meltzer, H. Y (1989) Clinical studies on the mechanism of action of clozapme the dopamine-serotonin hypothesis of schizophrenia Psychopharmacology 99, s l ~ s27 Szymanski, S, Lieberman, J, Pollack. S, Munne, R, Safferman, A, Kane, J, Kromg, M and Cooper T (lgg3) The dopamine-serotonm relationship in clozapine response Psychopharmacology 112, s85-s89
Clinical efficacy of clozapine in treatment-refractory ach,zophrenic patients Min-Soo Lee, In-Kwa Jung. Dong-II Kwak. Department of Psychiat~/,, Korea University College of Medicine 126-1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-705, Korea Clozapine, an atypical antipsychotic drug. has been estimated to be a malor improvement in the treatment-refractory schizophrenic patients. We eval uated the clozapine's efficacy in the treatment of Korean schizophrenic patients who are refractory to classical neuroleptics The patients were assigned in a prospective, open, comparative trial for 12 weeks. Following an dose titration, thirty-three inpatients with treatment-refractory schizophrenia diagnosed according to DSM-III-R were given a clozapine (N 17, approximate 300-600 mg/day) or haloperidol (N - 16; approximate 20-30 mg/day) for 12 w e e k s The clinical state was assessed before treatment. and 1st week, 4th week, 8th week, and 12th week during treatment using Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANNS). Blood samples were obtained before treatment, and 4th week, 8th week, and 12th week during treatment. Clozapine produced significant improvement than haloperidol on the BPRS and PANNS scores 77% (13/17) of the clozapine-treated patients were categorized as responders, who showed at least 20% decrease in total BPRS scores, compared with 31% (5/16} of haIoperidol-treated patients. There was no significant changes in total WBC and neutrophil during clozapine treatment. These findings suggest that clozapine is an effective antipsychotic drug for the Korean treatment-refractory schizophrenic patients, who are nonresponsive to classical antipsychotic drugs.
References Kane. J., Honigfeld, G, Singer, J, Meltzer, H.Y, the Clozard Collaborative Study Group {1988). CIozapine for the treatment-resistant schizophrenic: a double-blind companson with chlorpromazine Arch Gen Psychiatry45, 789-796 Kane. J.M., Safferman, A.Z, Pollack, S . Johns, C , Szymanski, S, Kronig, M , Lieberman, J A (1994) Clozapine. negative symptoms and extrapyramidal side effects J Clip PsychiatH 55, s74 s77
The role played by clozapine in the psycho-social rehabilitation program for chronic schizophrenic patients who present mostly negative symptoms M C. Nicotra, F Bilone, C A Robotti.
tst Psychiatric Service, Main Genera/
Hospital, Verona, Italy in the literature there is the evidence that about 40-50% of schizophrenics develop a serious and long-term disability in the social functioning 2 to the illness. While posqtive symptoms tend to the controlled with appropn ate psychopharmacological therapies, negative symptoms, which account
Improvement of positive and negative symptoms during clozapine treatment in neuroleptm-resistant schizophrenics I. Jalenques, E. Albuisson 1. Service de Psych/atrie A, CHU Saint-Jacques, BP 69, 63003 Clermont-Ferrand, F," 1 Service de Biostat~stiques, Facult# de M@decme, 28, Place Henri Dunant, 63000 Clermont-Ferrand, F
Friedman's test
Wilcoxon's test and decrease (%) between day 0 and day x
Total 8PRS BPRS positive symptoms BPRS anergia factor
p p p p
p p p p
BPRS item: depressive mood
NS
-
-
PANSS positive symptoms PANSS negative symptoms
p < 00001 p < 0 0001
p < 0,01 p < 0.01
(x - 15; 19.43%) (x = 30; 13.71%)
ESRS Dyskinesla Parkinsonism
NS NS NS
p < 007 p < 006
(x - 30; 2493%) (x = 90; 21 05%} -
Dystoma
NS
< < < <
00001 00001 00001 00001
< < < <
0.01 0.01 0.02 0.01
{x = (x = (x = (x -
15; 15: 30; 15:
16.45%) 14.18%) 17.78%) 11.70%)
-
Improvement ~n negative symptoms was significantly correlated to improvement in positive ones (BPRS positive symptoms/anergia factor: r = 055, p < 0.05; PANSS positive/negative subscales: r = 0.89, p = 0.0001), and to scores in ESRS (BPRS anergia factor: r = 0.61, p = 0.02; PANSS negative symptoms r = 0.62; p < 0.02), while it was independent from scores in subscale of depression (r = 0.25; p = 0.4). Clozapine's great efficacy on negative symptoms may be related to its great efficacy on positive symptoms in otherwise neuroleptic-refractory schizophrenics and to its low propensity to cause extrapyramidal sideeffects
References Jalenques I, Coudert A J (19941. Clozapine et schizophr@nies r@sistantes. Etude prospecnve ~ long terme chez vingt patients Enc@phaleXX, 767-75.
P-4 Antipsychotics." basic and clinical studies
were admitted to the inpatient serwce and withdrawn from all neuroleptlcs (except occasional doses of Iorazepam if needed for behavioral control) for 7-14 days. Ciozapine was started gradually on a once daily schedule: the dose was titrated as tolerated to 800 mg/day. The monoamine metabolites homovanillic acid (HVA). 5-hydroxy-indoleacetic acid (6-HIAA), and serotonin (5-HT) were measured in plasma before treatment and 2 weeks, 4 weeks, 8 weeks, 12 weeks during treatment. The plasma samples were aliquoted and frozen at - 7 0 ° C until assayed for HVA, 5-HIAA, 5-HT by high-performance liquid chromatography with electrochemical detection. Psychopathology was assessed with Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS) before and during Clozapine treatment. The mean (SD} age of the patients was 27.88 (7.38) years and the age of onset was 20.38 4- 4.90 years. Mean daily clozapine dosage were: at 4 weeks, 276,56 5 : 1 0 1 . 4 3 mg; at 8 weeks, 532.81 4- 98.86 mg; at 12 weeks, 584.38 4- 97.23 mg. During Clozapine treatment only small changes between baseline and following 2 weeks. 4 weeks 8 weeks 12 weeks HVA. 5-HIAA and 5-HT were found. However the change in serotonin index (6-HIAA/5-HT) from baseline to 4 weeks was statistically significant During treatment HVA 5-H IAA and 5-HT were not associated with psychopathology. These results suggest that Clozapine has been found to have relatively weak dopaminergic blockade and stronger serotonergic antagonism
more for poor social relations, can get worse progressively resulting in social with drawl and frequent hospitalizations. Many studies support the evidence that schizophrenic subjects receive a benefit from an integrated treatment with antipsychotic drugs and psychosocial rehabilitation. Better outcomes both in the spheres of clinical symptoms and social performance have been observed from the authors, using BPRS, SAPS, SANS and WHO/DAS in a group of chronic schizophrenics treated with clozapine. For the patients, with a history of several failures, it was possible either to plan and to put into practice psychosocial recovery, e.g. attending a residential therapeutic rehabilitation center, after a treatment with an average dose of 450 mg clozapine from 6 up to 18 months.
References
Poor response to neuroleptics is usually considered as a characteristic feature of negative symptoms of schizophrenia. Clozapine offers particular benefits for treatment-resistant schizophrenic patients in spite of the increased hematologic risk which restricts the use of clozapine to selected patients. Many studies concluded in its potent antipsychotic activity on positive symptoms of schizophrenia. The question whether negative symptoms of schizophrenia are also improved, concomitantly or independently of improvement in positive symptoms or of decrease in extrapyramidal side effects and/or depressive symptoms, remains unanswered. The authors prospectively followed up for 30 months. 13 DSM-IV resistant schizophrenics. Positive and negative symptoms were assessed by means of 1 8 item Brief Psychiatric Rating Scale (BPRS)(total and subscales: positive, cognitive, anergia and depressive mood), Positive and Negative Syndrome Scale (PANSS) positive as well as negative subscales, and Extrapyramidal Symptom Rating Scale (ESRS) prior to beginning on clozapine, at days 15. 30, 60 and 90, and further every 3 months. Friedman's test, Wilcoxon's test and Spearman's rank correlation coefficient were used to explore psychiatric ratings. Significant improvements, were noted in all psychiatric scales.
Meltzer, H. Y (1989) Clinical studies on the mechanism of action of clozapme the dopamine-serotonin hypothesis of schizophrenia Psychopharmacology 99, s l ~ s27 Szymanski, S, Lieberman, J, Pollack. S, Munne, R, Safferman, A, Kane, J, Kromg, M and Cooper T (lgg3) The dopamine-serotonm relationship in clozapine response Psychopharmacology 112, s85-s89
Clinical efficacy of clozapine in treatment-refractory ach,zophrenic patients Min-Soo Lee, In-Kwa Jung. Dong-II Kwak. Department of Psychiat~/,, Korea University College of Medicine 126-1, 5-Ka, Anam-Dong, Sungbuk-Ku, Seoul 136-705, Korea Clozapine, an atypical antipsychotic drug. has been estimated to be a malor improvement in the treatment-refractory schizophrenic patients. We eval uated the clozapine's efficacy in the treatment of Korean schizophrenic patients who are refractory to classical neuroleptics The patients were assigned in a prospective, open, comparative trial for 12 weeks. Following an dose titration, thirty-three inpatients with treatment-refractory schizophrenia diagnosed according to DSM-III-R were given a clozapine (N 17, approximate 300-600 mg/day) or haloperidol (N - 16; approximate 20-30 mg/day) for 12 w e e k s The clinical state was assessed before treatment. and 1st week, 4th week, 8th week, and 12th week during treatment using Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANNS). Blood samples were obtained before treatment, and 4th week, 8th week, and 12th week during treatment. Clozapine produced significant improvement than haloperidol on the BPRS and PANNS scores 77% (13/17) of the clozapine-treated patients were categorized as responders, who showed at least 20% decrease in total BPRS scores, compared with 31% (5/16} of haIoperidol-treated patients. There was no significant changes in total WBC and neutrophil during clozapine treatment. These findings suggest that clozapine is an effective antipsychotic drug for the Korean treatment-refractory schizophrenic patients, who are nonresponsive to classical antipsychotic drugs.
References Kane. J., Honigfeld, G, Singer, J, Meltzer, H.Y, the Clozard Collaborative Study Group {1988). CIozapine for the treatment-resistant schizophrenic: a double-blind companson with chlorpromazine Arch Gen Psychiatry45, 789-796 Kane. J.M., Safferman, A.Z, Pollack, S . Johns, C , Szymanski, S, Kronig, M , Lieberman, J A (1994) Clozapine. negative symptoms and extrapyramidal side effects J Clip PsychiatH 55, s74 s77
The role played by clozapine in the psycho-social rehabilitation program for chronic schizophrenic patients who present mostly negative symptoms M C. Nicotra, F Bilone, C A Robotti.
tst Psychiatric Service, Main Genera/
Hospital, Verona, Italy in the literature there is the evidence that about 40-50% of schizophrenics develop a serious and long-term disability in the social functioning 2 to the illness. While posqtive symptoms tend to the controlled with appropn ate psychopharmacological therapies, negative symptoms, which account
Improvement of positive and negative symptoms during clozapine treatment in neuroleptm-resistant schizophrenics I. Jalenques, E. Albuisson 1. Service de Psych/atrie A, CHU Saint-Jacques, BP 69, 63003 Clermont-Ferrand, F," 1 Service de Biostat~stiques, Facult# de M@decme, 28, Place Henri Dunant, 63000 Clermont-Ferrand, F
Friedman's test
Wilcoxon's test and decrease (%) between day 0 and day x
Total 8PRS BPRS positive symptoms BPRS anergia factor
p p p p
p p p p
BPRS item: depressive mood
NS
-
-
PANSS positive symptoms PANSS negative symptoms
p < 00001 p < 0 0001
p < 0,01 p < 0.01
(x - 15; 19.43%) (x = 30; 13.71%)
ESRS Dyskinesla Parkinsonism
NS NS NS
p < 007 p < 006
(x - 30; 2493%) (x = 90; 21 05%} -
Dystoma
NS
< < < <
00001 00001 00001 00001
< < < <
0.01 0.01 0.02 0.01
{x = (x = (x = (x -
15; 15: 30; 15:
16.45%) 14.18%) 17.78%) 11.70%)
-
Improvement ~n negative symptoms was significantly correlated to improvement in positive ones (BPRS positive symptoms/anergia factor: r = 055, p < 0.05; PANSS positive/negative subscales: r = 0.89, p = 0.0001), and to scores in ESRS (BPRS anergia factor: r = 0.61, p = 0.02; PANSS negative symptoms r = 0.62; p < 0.02), while it was independent from scores in subscale of depression (r = 0.25; p = 0.4). Clozapine's great efficacy on negative symptoms may be related to its great efficacy on positive symptoms in otherwise neuroleptic-refractory schizophrenics and to its low propensity to cause extrapyramidal sideeffects
References Jalenques I, Coudert A J (19941. Clozapine et schizophr@nies r@sistantes. Etude prospecnve ~ long terme chez vingt patients Enc@phaleXX, 767-75.