Clozapine
Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a l...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Fitton, Andrew [verfasserIn] Benfield, Paul [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
1993 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: PharmacoEconomics - Berlin [u.a.] : Springer, 1992, 4(1993), 2 vom: Aug., Seite 131-156 |
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| Übergeordnetes Werk: |
volume:4 ; year:1993 ; number:2 ; month:08 ; pages:131-156 |
| Links: |
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| DOI / URN: |
10.2165/00019053-199304020-00007 |
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| Katalog-ID: |
SPR033319391 |
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| 520 | |a Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... | ||
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| 650 | 4 | |a Clozapine |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Tardive Dyskinesia |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Clozapine Therapy |7 (dpeaa)DE-He213 | |
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10.2165/00019053-199304020-00007 doi (DE-627)SPR033319391 (SPR)00019053-199304020-00007-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Fitton, Andrew verfasserin aut Clozapine 1993 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... Schizophrenia (dpeaa)DE-He213 Clozapine (dpeaa)DE-He213 Tardive Dyskinesia (dpeaa)DE-He213 Clozapine Therapy (dpeaa)DE-He213 Direct Treatment Cost (dpeaa)DE-He213 Benfield, Paul verfasserin aut Enthalten in PharmacoEconomics Berlin [u.a.] : Springer, 1992 4(1993), 2 vom: Aug., Seite 131-156 (DE-627)327645717 (DE-600)2043876-X 1179-2027 nnns volume:4 year:1993 number:2 month:08 pages:131-156 https://dx.doi.org/10.2165/00019053-199304020-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 44.40 ASE AR 4 1993 2 08 131-156 |
| spelling |
10.2165/00019053-199304020-00007 doi (DE-627)SPR033319391 (SPR)00019053-199304020-00007-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Fitton, Andrew verfasserin aut Clozapine 1993 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... Schizophrenia (dpeaa)DE-He213 Clozapine (dpeaa)DE-He213 Tardive Dyskinesia (dpeaa)DE-He213 Clozapine Therapy (dpeaa)DE-He213 Direct Treatment Cost (dpeaa)DE-He213 Benfield, Paul verfasserin aut Enthalten in PharmacoEconomics Berlin [u.a.] : Springer, 1992 4(1993), 2 vom: Aug., Seite 131-156 (DE-627)327645717 (DE-600)2043876-X 1179-2027 nnns volume:4 year:1993 number:2 month:08 pages:131-156 https://dx.doi.org/10.2165/00019053-199304020-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 44.40 ASE AR 4 1993 2 08 131-156 |
| allfields_unstemmed |
10.2165/00019053-199304020-00007 doi (DE-627)SPR033319391 (SPR)00019053-199304020-00007-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Fitton, Andrew verfasserin aut Clozapine 1993 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... Schizophrenia (dpeaa)DE-He213 Clozapine (dpeaa)DE-He213 Tardive Dyskinesia (dpeaa)DE-He213 Clozapine Therapy (dpeaa)DE-He213 Direct Treatment Cost (dpeaa)DE-He213 Benfield, Paul verfasserin aut Enthalten in PharmacoEconomics Berlin [u.a.] : Springer, 1992 4(1993), 2 vom: Aug., Seite 131-156 (DE-627)327645717 (DE-600)2043876-X 1179-2027 nnns volume:4 year:1993 number:2 month:08 pages:131-156 https://dx.doi.org/10.2165/00019053-199304020-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 44.40 ASE AR 4 1993 2 08 131-156 |
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10.2165/00019053-199304020-00007 doi (DE-627)SPR033319391 (SPR)00019053-199304020-00007-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Fitton, Andrew verfasserin aut Clozapine 1993 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... Schizophrenia (dpeaa)DE-He213 Clozapine (dpeaa)DE-He213 Tardive Dyskinesia (dpeaa)DE-He213 Clozapine Therapy (dpeaa)DE-He213 Direct Treatment Cost (dpeaa)DE-He213 Benfield, Paul verfasserin aut Enthalten in PharmacoEconomics Berlin [u.a.] : Springer, 1992 4(1993), 2 vom: Aug., Seite 131-156 (DE-627)327645717 (DE-600)2043876-X 1179-2027 nnns volume:4 year:1993 number:2 month:08 pages:131-156 https://dx.doi.org/10.2165/00019053-199304020-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 44.40 ASE AR 4 1993 2 08 131-156 |
| allfieldsSound |
10.2165/00019053-199304020-00007 doi (DE-627)SPR033319391 (SPR)00019053-199304020-00007-e DE-627 ger DE-627 rakwb eng 610 ASE 44.40 bkl Fitton, Andrew verfasserin aut Clozapine 1993 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... Schizophrenia (dpeaa)DE-He213 Clozapine (dpeaa)DE-He213 Tardive Dyskinesia (dpeaa)DE-He213 Clozapine Therapy (dpeaa)DE-He213 Direct Treatment Cost (dpeaa)DE-He213 Benfield, Paul verfasserin aut Enthalten in PharmacoEconomics Berlin [u.a.] : Springer, 1992 4(1993), 2 vom: Aug., Seite 131-156 (DE-627)327645717 (DE-600)2043876-X 1179-2027 nnns volume:4 year:1993 number:2 month:08 pages:131-156 https://dx.doi.org/10.2165/00019053-199304020-00007 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_702 GBV_ILN_2190 44.40 ASE AR 4 1993 2 08 131-156 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR033319391</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519200600.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s1993 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.2165/00019053-199304020-00007</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR033319391</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)00019053-199304020-00007-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.40</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Fitton, Andrew</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Clozapine</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">1993</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y...</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Schizophrenia</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Clozapine</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tardive Dyskinesia</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Clozapine Therapy</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Direct Treatment Cost</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Benfield, Paul</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">PharmacoEconomics</subfield><subfield code="d">Berlin [u.a.] : Springer, 1992</subfield><subfield code="g">4(1993), 2 vom: Aug., Seite 131-156</subfield><subfield code="w">(DE-627)327645717</subfield><subfield code="w">(DE-600)2043876-X</subfield><subfield code="x">1179-2027</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:4</subfield><subfield code="g">year:1993</subfield><subfield code="g">number:2</subfield><subfield code="g">month:08</subfield><subfield code="g">pages:131-156</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.2165/00019053-199304020-00007</subfield><subfield code="z">lizenzpflichtig</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-ASE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2190</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.40</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">4</subfield><subfield code="j">1993</subfield><subfield code="e">2</subfield><subfield code="c">08</subfield><subfield code="h">131-156</subfield></datafield></record></collection>
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| abstract |
Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... |
| abstractGer |
Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... |
| abstract_unstemmed |
Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. Cost analysis, based on an initial hospitalisation period of 2 to 4 weeks (for withdrawal of existing antipsychotic therapy and the switch to clozapine). indicates that, compared with standard antipsychotics, clozapine might save between $US934 and $US7505 per patient over the first 2 y... |
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Clozapine |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR033319391</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519200600.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s1993 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.2165/00019053-199304020-00007</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR033319391</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)00019053-199304020-00007-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.40</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Fitton, Andrew</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Clozapine</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">1993</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up 10 60%) of patients who are refractory to or intolerant of standard anlipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (≈1% of patients) and the associated need for regular haematological monitoring currently restricts the drug’s use to the treatment of chronic and severe schizophrenia refractory 10 standard antipsychotic therapy, and of those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting of $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually 10 state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term (≥ 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers. Disease Considerations Disease course and treatment outcome vary considerably in schizophrenia, a fact attributable to the probable heterogeneity of schizophrenia, and differences in patient age group and duration of follow-up. Among newly diagnosed cases, one-quarter to one-third lead to long lasting remission (with or without residual symptoms), approximately 20% have further episodes of illness with symptom-free intervals, and the remainder progress to moderate or severe chronic psychoses with marked personality changes. Schizophrenia in men is typically associated with early onset (mean age 21 years) and chronicity, whereas in women it tends to be of later onset (mean age 27 years) and to follow a remitting course. The prevalence of treatment-resistant schizophrenia ranges from 5 to 30% of patients. Frequently classified with drug-refractory patients are those intolerant of standard antipsychotics because of the development of severe extrapyramidal symptoms, and the estimated 20 to 40% of patients who develop tardive dyskinesia on long term therapy. Clinical options for the management of treatment-resistant schizophrenia are limited: common clinical practice is to increase the existing antipsychotic dose or to switch to a different class of antipsychotic. Possible adjunctive and alternative treatments include lithium, high-dose benzodiazepines, and electroconvulsive therapy. Clozapine currently appears to be the most effective antipsychotic for treatment-resistant schizophrenia and, but for its associated risk of agranulocytosis, should probably be regarded as the drug of first choice for the majority of patients. Efficacy and Tolerability Noncomparative studies have indicated that clozapine is of significant clinical benefit in a substantial proportion (up to 60%) of patients with treatment-resistant schizophrenia, producing improvements in both positive and negative symptoms and the quality of life (including interpersonal relationships and social function) after 1.5 to 6 months of therapy, and enhanced social adaptation and a reduced need for rehospitalisation on long term (6 months to ≥ 2 years) therapy. The most pronounced improvement in psychopathology frequently occurs during the first 6 weeks of clozapine therapy, with further gradual improvement seen on maintenance therapy. Short term (6 to 8 weeks) double-blind comparative studies have provided evidence of the superior antipsychotic efficacy of clozapine (≤ 900 mg/day) versus that of chlorpromazine (≤ 1800 mg/day) in treatment-resistant schizophrenia. Although patients intolerant of standard antipsychotics generally respond better to clozapine therapy than those refractory to previous antipsychotic therapy, no reliable aetiological or clinical predictors of therapeutic response to clozapine in treatment-resistant schizophrenia have been identified. Clozapine is distinguished from standard antipsychotics by its relatively low incidence of extrapyramidal effects, of which akathisia, akinesia and tremor (≈ 6% of patients) appear to predominate over dystonia. Tardive dyskinesia has not been reported to date with long term dozapine therapy. Agranulocytosis is the most serious adverse effect of dozapine, occurrina in ≈1% of patients and requiring immediate drug discontinuation. This dyscrasia is usually of gradual onset, with maximum risk arising during the first 18 weeks of therapy; predisposing factors remain undetermined. Pharmacoeconomic Considerations The costs of schizophrenia to society can be divided into direct treatment costs (inpatient and outpatient care, residential care, community-based services, and drug therapy), indirect costs (lost productivity and earnings due 10 illness and/or early moratily), and intangibles (e.g. suffering experienced by the patient and family). The average annual direct treatment cost of schizophrenia in the UK is estimated at approximately £1670 per person (1987 pounds), with hospital inpatient care (£572), other residential care (£662) and day care (£228) constituting the major items of expenditure; drug therapy (£56) represents a relatively minor component. On a national scale. the direct and indirect monetary cost of schizophrenia amounts to approximately £1600 million (range £1000 million to £2700 million) annually (1987 pounds), while the total lifetime cost (from disease onset to death) generated by new cases of schizophrenia amounts to £1204 million annually. In the Us, annual direct and indirect costs of treatment-resistant schizophrenia range from $US11 300 to 22 600 million and from $US4600 to 9200 million, respectively (1987 dollars), representing a total annual cost of $US66 135 per patient. Introduced in the US in 1990. clozapine was initially linked or ‘bundled’ with a proprietary drug monitoring and distribution system, the Clozaril® Patient Monitoring System (CPMS). This arrangement, unique in US pharmaceutical history, was held to be largely responsible for the high cost of clozapine ($US8944 per patient annually (1990 dollars), reflecting the manufacturer’s charge for the drug and the mandatory services of the CPMS]. Since May 1991 clozapine has been ‘unbundled’ in the US, and mandatory blood monitoring and drug distribution is now permissible through alternative agencies. Under this new arrangement the acquisition cost of the drug ($US2.85 per 100mg tablet) has been separated from the monitoring cost (unspecified). This translates into an annual treatment cost (exclusive of monitoring) of $US4160 (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US3510 to state programmes through Medicaid reimbursement legislation). While Medicaid coverage of clozapine has been available in all 50 US states since 1991, expansion in use of the drug has been slow. Of the 133 000 patients conservatively estimated to be eligible for clozapine treatment in the US, approximately 44 000 are currently receiving it. In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is £1806 (1992 pounds) [or £2400 at a dose of 400 mg/day]. The limited US cost-effectiveness data available to date suggest that the dinical benefits associated with clozapine therapy in patients with treatment-resistant schizophrenia (viz. improved psychopathology, social functioning and quality of life) may result in medium to long term economic benefits, primarily as a result of reduced use of psychiatric and general hospital services. 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