- Email: [email protected]
P.3.c.057 Which patients switch antipsychotic medication? Data from the international Antipsychotic Drug Substitution Registry
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P.3.c. Psychotic disorders and antipsychotics − Antipsychotics (clinical)
(Cmax ) at 5 and 10 mg BID, as measured by the geometric mean, were 4.73 and 7.93 ng/mL. Areas under the curve from 0−12 hours at 5 and 10 mg BID were 32.1 and 56.3 ng·h/mL. Conclusions: Compared with previous findings in patients aged <65 years (asenapine Cmax: 4.23 ng/mL at 5 mg BID, 6.56 ng/mL at 10 mg BID), exposure was 12−30% higher in elderly patients, indicating lower drug clearance in this population. Despite the increased exposure, short-term asenapine treatment was generally well tolerated in elderly patients with psychosis during rapid dosage escalation. Disclosure statement: Research support from Pfizer, Otsuka, Sumitomo Pharma, Biogen, and Tower Foundation. P.3.c.056 Prolactin elevation induced by antipsychotics in first episode psychotic patients R. Perez-Iglesias1 ° , I. Mata1 , M.T. Garcia-Unzueta2 , J.A. Amado3 , O. Martinez-Garcia1 , J.L. Vazquez-Barquero1 , 1 Hospital Universitario Marques de B. Crespo-Facorro1 . Valdecilla, Psiquiatria, Santander, Spain; 2 Hospital Universitario Marques de Valdecilla, Analisis clinicos, Santander, Spain; 3 Hospital Universitario Marques de Valdecilla, Endocrinolog´ıa, Santander, Spain Purpose: The prevalence rate of hyperprolactinemia in patients taking antipsychotic is considerably higher than the prevalence rate of general population. Although prolactin levels are not routinely obtained, this association may have long-term consequences in terms of menstrual disturbances, sexual dysfunction and lower bone mineral density. There are few data comparing the effect of low doses of antipsychotics on prolactin levels in first episode psychotic patients. The main objective of this study was to compare the effect of typical (haloperidol) an atypical (olanzapine and risperidone) antipsychotics on serum prolactin levels during the first 3 months of treatment. Method: A randomized, open-label, prospective clinical trial was conducted. Participants were 145 consecutive first episode psychotic patients included in a first episode program of Cantabria (Spain) from February 2002 to February 2005. Patients have not been previously exposed to antipsychotic medication. The rate of participation was 98.6% and the number of patients who remained adherent with the protocol after 12 weeks was 88.3%. Prolactin levels were measured by chemiluminiscent automathed assay in a Advia Centaur Chemistry System from Bayer Diagnostics (Bayer Corporation, Tarrytown, NY, USA), using the reagents supplied by Boehringer-Mannheim (Mannheim, Germany). Normal values were <12.5 ng/ml for men and <18.5 ng/ml for women. Results: Mean dose of antipsychotics at 3 months were: 4.2 mg/d haloperidol, 12.7 mg/d of olanzapine and 3.6 mg/d of risperidone. The mean prolactin levels at baseline were: 34.1 ng/ml for haloperidol group, 26.0 ng/ml for olanzapine and 35.7 ng/ml for risperidone. At 3 months the prolactin levels were: 22.8 ng/ml for haloperidol group, 23.1 ng/ml for olanzapine and 72.5 ng/ml for risperidone. Patients treated with risperidone experienced a significantly increase in prolactin levels compared with both olanzapine and haloperidol treatments (F = 39.1, df = 2, p < 0.001). The increment from baseline levels in risperidone group was 97% (65.4% in men and 133.9% in women) resulting in abnormal plasma prolactin levels at 3 months in 92.3% of men and 100% of women. It is noteworthy that although risperidone is the only treatment that produces increase in prolactin levels in our study, the three groups of treatment showed high levels of prolactin
at baseline and at 3 months. One possible explanation for the high prolactin levels, even at baseline, is that some patients had received their first dose of treatment the night before the blood test was performed. Another factor that could have influenced the prolactin levels is the stress experienced at the moment of admission. Despite the elevated percentage of patients with abnormal prolactin levels, few patients reported prolactin-related side effects: only 2 patients reported galacthorrea, both treated with risperidone, 4 patients reported amenorrhea (2 treated with haloperidol y 2 treated with risperidone) and 15 patients reported sexual side effects (6 treated with haloperidol, 3 treated with olanzapine and 6 treated with risperidone). Only 1 patient in risperidone treatment group needed change to a different treatment because the severity of sexual side effects. Conclusions: Serum prolactin levels should be monitored during risperidone treatment and sexual side effects should be inquired. References [1] Haddad, PM, Wieck, A (2004) Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs, 64(20): 2291–2314. [2] Melkersson, K (2005) Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J Clin Psychiatry, 66(6): 761–767. [3] Volavka, J, Czobor, P, Cooper, TB, Sheitman, B, Lindenmayer, JP, Citrome, L, McEvoy, JP, Lieberman, JA (2004) Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychiatry, 65(1): 57−61.
P.3.c.057 Which patients switch antipsychotic medication? Data from the international Antipsychotic Drug Substitution Registry P. Paterakis1 ° , B. Galinska-Skok2 , L. Pani3 , M. Bubrovszky4 , 1 “Dromokaitio” Psychiatric G. Perdriset5 , P. Thomas4 . General Hospital of Athens, Department of psychiatry, Athens, Greece; 2 Medical University of Bialystok, Department of psychiatry, Choroszcz, Poland; 3 Institute Biomedical Technologies PharmaNess Scarl, Neuropharmacology Section, Cagliari, Italy; 4 Hˆ opital Fontan − CHRU de Lille, Department of psychiatry, Lille, France; 5 sanofi-aventis, Medical Affairs Department, Paris, France Purpose of the study: Around one-third of patients treated with antipsychotic drugs change their medication every year. The frequency of switch varies among countries depending on the local medical practice and is likely to vary between different antipsychotic drug classes. A naturalistic, multinational observational survey (SWITCH) has been implemented to evaluate the dynamics of treatment discontinuation and substitution in the management of schizophrenia in everyday clinical practice. The primary objective of this study was to identify the frequency of switching antipsychotic treatments in patients with schizophrenia. A secondary objective was to identify reasons for switch to other antipsychotic. Methods used: This was a cross-sectional, observational study performed in eleven countries (Algeria, Greece, India, Jordan, Lithuania, Mexico, Philippines, Poland, Slovakia, Ukraine and Vietnam). All adult patients with schizophrenia consulting consecutively within one month (up to fifty per site) were included in the study. These patients constituted the Screening population. Data was collected on socio-demographics, psychiatric diagnosis
P.3.c. Psychotic disorders and antipsychotics − Antipsychotics (clinical) and medical history and treatment. Patients for whom a switch in antipsychotic treatment had been deemed necessary in the previous twelve weeks were identified and these constituted the Switch population. Patients from the ‘Switch population’ as well as percentage of switch per country are described and presented here. Summary of results: The Screening population was composed of 23 441 patients. 40.9% of patients were from Poland, 14.4% from Slovakia, 11.0% from India and 10.7% from Algeria. Of these patients, 22 126 patients were included in the primary analysis population, and 5128 patients reported a treatment switch in the previous twelve weeks patients. Overall, the percentage of patients switching treatment in the previous twelve weeks was 23.2%. However, this composite figure masked significant variation between different countries participating in the study (p < 0.0001; c2 test). The switch rate was higher in countries which included a higher percentage of inpatients. Switch rates ranged from 11.9% in India to 68.1% in Ukraine, which have 10% and 85% of inpatients respectively. Switch rates were highest in patients who had received a diagnosis of paranoid schizophrenia (70.4%). The global incidence of switching also varied according to gender and age. Switching was more frequent in women (24.2% vs 22.5% in men, p = 0.002; c2 test) and patients who switched were younger (mean age: 39.2±12.6 years) than patients who did not (41.2±13.1 years, p < 0.0001 Mann-Whitney U-test); the highest rate of switching was observed in the 22−29 yr age group, the rate declining with age thereafter. Conclusions: In this study, switching between antipsychotic drug treatment regimens was frequent, with on average one in five of patients consulting having switched therapy in the previous twelve weeks. Switch rates varied significantly between countries, were highest in inpatients, women and younger patients. P.3.c.058 Clozapine-induced agranulocytosis in monozygotic twins and association with multidrug resistance gene MDR1 polymorphisms A.E. Anil Yagcioglu1 ° , B. Cetin Ilhan1 , M.T. Goktas2 , M.O. Babaoglu2 , E. Uz3 , M.K. Yazici1 . 1 Hacettepe University Faculty of Medicine, Department of Psychiatry, Ankara, Turkey; 2 Hacettepe University Faculty of Medicine, Department of Pharmacology, Ankara, Turkey; 3 Hacettepe University Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey Despite its proven superior efficacy in treatment resistant schizophrenia, clozapine’s use has been limited by the serious side effect of agranulocytosis. This adverse event has been suggested to be immune mediated or due to toxic or apoptotic effects mediated by clozapine or its metabolites which are determined by genetic factors [1]. Clozapine’s oxidation to a toxic nitrenium ion has been implicated in the pathogenesis of agranulocytosis. In addition, clozapine and possibly its metabolites interact with the multidrug resistance transporter (MDR1) gene product, P-glycoprotein, which is highly expressed in leukocytes. Among various polymorphisms C3435T and G2677T have been shown to alter the function of this transporter [2]. However, there are no investigations regarding the role of these MDR1 polymorphisms in clozapine-induced agranulocytosis. We present a case report of clozapine-induced agranulocytosis in monozygotic twins with schizophrenia as evidence for a genetic basis of this adverse event. Further, we have also genotyped these patients regarding MDR1 polymorphisms.
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Thirty-four year old twin brothers have been followed at the outpatient clinic of Hacettepe University Faculty of Medicine, Department of Psychiatry with a diagnosis of paranoid schizophrenia. Twin I developed clozapine-induced agranulocytosis at the age of 26, on the 5th week of treatment, receiving 200 mg/day of clozapine. His routine leukocyte count was found to be 1900/mm3 (260/mm3 neutrophils) and clozapine was discontinued. No fever or other complications were observed. Twin II developed clozapine-induced agranulocytosis at the age of 33, on the 6th month of treatment, receiving 500 mg/day of clozapine. His leukocyte count was found to be 1500/mm3 (183/mm3 neutrophils) and was admitted to the inpatient psychiatry clinic, developing a fever of 38.6 ºC on the 4th day of agranulocytosis. He was isolated and treated with antibiotics, an antiviral and granulocyte-stimulating growth factor analog (G-CSF). G-CSF was discontinued in 6 days. Both patients had showed their best treatment response on clozapine. After the onset of clozapine-induced agranulocytosis in the second twin, venous blood sample was collected from both patients for DNA extraction. Genotyping results of Affymetrix GeneChip Mapping 250 K SNP Chip revealed a genotype consensus of 96.2% confirming the monozygotic status. In addition, the twin patients were genotyped for MDR1 C3435T and G2677T genetic variants and found to be heterozygotes, i.e. CT and GT, respectively for both C3435T and G2677T polymorphisms. To our knowledge, this is the second report of clozapineinduced agranulocytosis in monozygotic twins. Contrary to the first report [3], our report suggests that the timing of agranulocytosis in monozygotic twins can vary. If a monozygotic twin sibling has a history of clozapine-induced agranulocytosis, the other sibling should not be started on clozapine before zygosity is determined. Our genotyping results also suggest that the existence of both C3435T and G2677T MDR1 polymorphisms might have led to an additive functional loss in P-glycoprotein action, resulting in toxic metabolite accumulation in leukocytes and thus agranulocytosis. Further investigations are necessary to clarify the role of MDR1 allelic variants on development of clozapineinduced agranulocytosis. References [1] Mosyagin, I., Dettling, M., Roots, I., et al., 2004 Impact of myeloperoxidase and NADPH-oxidase polymorphisms in drug-induced agranulocytosis. J Clin Psychopharmacol 24, 613–617. [2] Pauli-Magnus, C., Kroetz, D.L., 2004 Functional implications of genetic polymorphisms in the multidrug resistance gene MDR1 (ABCB1). Pharm Res 21, 904–913. [3] Horacek, J., Libiger, J., Hoschl, C. et al., 2001 Clozapine-induced concordant agranulocytosis in monozygotic twins. Int J Psychiatry Clin Pract 5, 71−73.
P.3.c.059 Oxidative stress status in schizophrenic patients treated with typical versus atypical antipsychotics M. Padurariu1 ° , I. Dobrin1 , C. Stefanescu1 , A. Ciobica2 , R.P. Dobrin1 . 1 Socola Hospital-Gr.T. Popa University of Medicine and Pharmacy, Dept. of Psychiatry, Iasi, Romania; 2 Al. I. Cuza University, Dept. of Biology, Iasi, Romania Introduction: Schizophrenia is a common psychiatric disorder, marked by gross distortion from reality; disturbances in thinking, feeling, and behavior. However, the chemical nature of the schizophrenic brain is still not completely understood.
P.3.c. Psychotic disorders and antipsychotics − Antipsychotics (clinical)
(Cmax ) at 5 and 10 mg BID, as measured by the geometric mean, were 4.73 and 7.93 ng/mL. Areas under the curve from 0−12 hours at 5 and 10 mg BID were 32.1 and 56.3 ng·h/mL. Conclusions: Compared with previous findings in patients aged <65 years (asenapine Cmax: 4.23 ng/mL at 5 mg BID, 6.56 ng/mL at 10 mg BID), exposure was 12−30% higher in elderly patients, indicating lower drug clearance in this population. Despite the increased exposure, short-term asenapine treatment was generally well tolerated in elderly patients with psychosis during rapid dosage escalation. Disclosure statement: Research support from Pfizer, Otsuka, Sumitomo Pharma, Biogen, and Tower Foundation. P.3.c.056 Prolactin elevation induced by antipsychotics in first episode psychotic patients R. Perez-Iglesias1 ° , I. Mata1 , M.T. Garcia-Unzueta2 , J.A. Amado3 , O. Martinez-Garcia1 , J.L. Vazquez-Barquero1 , 1 Hospital Universitario Marques de B. Crespo-Facorro1 . Valdecilla, Psiquiatria, Santander, Spain; 2 Hospital Universitario Marques de Valdecilla, Analisis clinicos, Santander, Spain; 3 Hospital Universitario Marques de Valdecilla, Endocrinolog´ıa, Santander, Spain Purpose: The prevalence rate of hyperprolactinemia in patients taking antipsychotic is considerably higher than the prevalence rate of general population. Although prolactin levels are not routinely obtained, this association may have long-term consequences in terms of menstrual disturbances, sexual dysfunction and lower bone mineral density. There are few data comparing the effect of low doses of antipsychotics on prolactin levels in first episode psychotic patients. The main objective of this study was to compare the effect of typical (haloperidol) an atypical (olanzapine and risperidone) antipsychotics on serum prolactin levels during the first 3 months of treatment. Method: A randomized, open-label, prospective clinical trial was conducted. Participants were 145 consecutive first episode psychotic patients included in a first episode program of Cantabria (Spain) from February 2002 to February 2005. Patients have not been previously exposed to antipsychotic medication. The rate of participation was 98.6% and the number of patients who remained adherent with the protocol after 12 weeks was 88.3%. Prolactin levels were measured by chemiluminiscent automathed assay in a Advia Centaur Chemistry System from Bayer Diagnostics (Bayer Corporation, Tarrytown, NY, USA), using the reagents supplied by Boehringer-Mannheim (Mannheim, Germany). Normal values were <12.5 ng/ml for men and <18.5 ng/ml for women. Results: Mean dose of antipsychotics at 3 months were: 4.2 mg/d haloperidol, 12.7 mg/d of olanzapine and 3.6 mg/d of risperidone. The mean prolactin levels at baseline were: 34.1 ng/ml for haloperidol group, 26.0 ng/ml for olanzapine and 35.7 ng/ml for risperidone. At 3 months the prolactin levels were: 22.8 ng/ml for haloperidol group, 23.1 ng/ml for olanzapine and 72.5 ng/ml for risperidone. Patients treated with risperidone experienced a significantly increase in prolactin levels compared with both olanzapine and haloperidol treatments (F = 39.1, df = 2, p < 0.001). The increment from baseline levels in risperidone group was 97% (65.4% in men and 133.9% in women) resulting in abnormal plasma prolactin levels at 3 months in 92.3% of men and 100% of women. It is noteworthy that although risperidone is the only treatment that produces increase in prolactin levels in our study, the three groups of treatment showed high levels of prolactin
at baseline and at 3 months. One possible explanation for the high prolactin levels, even at baseline, is that some patients had received their first dose of treatment the night before the blood test was performed. Another factor that could have influenced the prolactin levels is the stress experienced at the moment of admission. Despite the elevated percentage of patients with abnormal prolactin levels, few patients reported prolactin-related side effects: only 2 patients reported galacthorrea, both treated with risperidone, 4 patients reported amenorrhea (2 treated with haloperidol y 2 treated with risperidone) and 15 patients reported sexual side effects (6 treated with haloperidol, 3 treated with olanzapine and 6 treated with risperidone). Only 1 patient in risperidone treatment group needed change to a different treatment because the severity of sexual side effects. Conclusions: Serum prolactin levels should be monitored during risperidone treatment and sexual side effects should be inquired. References [1] Haddad, PM, Wieck, A (2004) Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs, 64(20): 2291–2314. [2] Melkersson, K (2005) Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J Clin Psychiatry, 66(6): 761–767. [3] Volavka, J, Czobor, P, Cooper, TB, Sheitman, B, Lindenmayer, JP, Citrome, L, McEvoy, JP, Lieberman, JA (2004) Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychiatry, 65(1): 57−61.
P.3.c.057 Which patients switch antipsychotic medication? Data from the international Antipsychotic Drug Substitution Registry P. Paterakis1 ° , B. Galinska-Skok2 , L. Pani3 , M. Bubrovszky4 , 1 “Dromokaitio” Psychiatric G. Perdriset5 , P. Thomas4 . General Hospital of Athens, Department of psychiatry, Athens, Greece; 2 Medical University of Bialystok, Department of psychiatry, Choroszcz, Poland; 3 Institute Biomedical Technologies PharmaNess Scarl, Neuropharmacology Section, Cagliari, Italy; 4 Hˆ opital Fontan − CHRU de Lille, Department of psychiatry, Lille, France; 5 sanofi-aventis, Medical Affairs Department, Paris, France Purpose of the study: Around one-third of patients treated with antipsychotic drugs change their medication every year. The frequency of switch varies among countries depending on the local medical practice and is likely to vary between different antipsychotic drug classes. A naturalistic, multinational observational survey (SWITCH) has been implemented to evaluate the dynamics of treatment discontinuation and substitution in the management of schizophrenia in everyday clinical practice. The primary objective of this study was to identify the frequency of switching antipsychotic treatments in patients with schizophrenia. A secondary objective was to identify reasons for switch to other antipsychotic. Methods used: This was a cross-sectional, observational study performed in eleven countries (Algeria, Greece, India, Jordan, Lithuania, Mexico, Philippines, Poland, Slovakia, Ukraine and Vietnam). All adult patients with schizophrenia consulting consecutively within one month (up to fifty per site) were included in the study. These patients constituted the Screening population. Data was collected on socio-demographics, psychiatric diagnosis
P.3.c. Psychotic disorders and antipsychotics − Antipsychotics (clinical) and medical history and treatment. Patients for whom a switch in antipsychotic treatment had been deemed necessary in the previous twelve weeks were identified and these constituted the Switch population. Patients from the ‘Switch population’ as well as percentage of switch per country are described and presented here. Summary of results: The Screening population was composed of 23 441 patients. 40.9% of patients were from Poland, 14.4% from Slovakia, 11.0% from India and 10.7% from Algeria. Of these patients, 22 126 patients were included in the primary analysis population, and 5128 patients reported a treatment switch in the previous twelve weeks patients. Overall, the percentage of patients switching treatment in the previous twelve weeks was 23.2%. However, this composite figure masked significant variation between different countries participating in the study (p < 0.0001; c2 test). The switch rate was higher in countries which included a higher percentage of inpatients. Switch rates ranged from 11.9% in India to 68.1% in Ukraine, which have 10% and 85% of inpatients respectively. Switch rates were highest in patients who had received a diagnosis of paranoid schizophrenia (70.4%). The global incidence of switching also varied according to gender and age. Switching was more frequent in women (24.2% vs 22.5% in men, p = 0.002; c2 test) and patients who switched were younger (mean age: 39.2±12.6 years) than patients who did not (41.2±13.1 years, p < 0.0001 Mann-Whitney U-test); the highest rate of switching was observed in the 22−29 yr age group, the rate declining with age thereafter. Conclusions: In this study, switching between antipsychotic drug treatment regimens was frequent, with on average one in five of patients consulting having switched therapy in the previous twelve weeks. Switch rates varied significantly between countries, were highest in inpatients, women and younger patients. P.3.c.058 Clozapine-induced agranulocytosis in monozygotic twins and association with multidrug resistance gene MDR1 polymorphisms A.E. Anil Yagcioglu1 ° , B. Cetin Ilhan1 , M.T. Goktas2 , M.O. Babaoglu2 , E. Uz3 , M.K. Yazici1 . 1 Hacettepe University Faculty of Medicine, Department of Psychiatry, Ankara, Turkey; 2 Hacettepe University Faculty of Medicine, Department of Pharmacology, Ankara, Turkey; 3 Hacettepe University Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey Despite its proven superior efficacy in treatment resistant schizophrenia, clozapine’s use has been limited by the serious side effect of agranulocytosis. This adverse event has been suggested to be immune mediated or due to toxic or apoptotic effects mediated by clozapine or its metabolites which are determined by genetic factors [1]. Clozapine’s oxidation to a toxic nitrenium ion has been implicated in the pathogenesis of agranulocytosis. In addition, clozapine and possibly its metabolites interact with the multidrug resistance transporter (MDR1) gene product, P-glycoprotein, which is highly expressed in leukocytes. Among various polymorphisms C3435T and G2677T have been shown to alter the function of this transporter [2]. However, there are no investigations regarding the role of these MDR1 polymorphisms in clozapine-induced agranulocytosis. We present a case report of clozapine-induced agranulocytosis in monozygotic twins with schizophrenia as evidence for a genetic basis of this adverse event. Further, we have also genotyped these patients regarding MDR1 polymorphisms.
S491
Thirty-four year old twin brothers have been followed at the outpatient clinic of Hacettepe University Faculty of Medicine, Department of Psychiatry with a diagnosis of paranoid schizophrenia. Twin I developed clozapine-induced agranulocytosis at the age of 26, on the 5th week of treatment, receiving 200 mg/day of clozapine. His routine leukocyte count was found to be 1900/mm3 (260/mm3 neutrophils) and clozapine was discontinued. No fever or other complications were observed. Twin II developed clozapine-induced agranulocytosis at the age of 33, on the 6th month of treatment, receiving 500 mg/day of clozapine. His leukocyte count was found to be 1500/mm3 (183/mm3 neutrophils) and was admitted to the inpatient psychiatry clinic, developing a fever of 38.6 ºC on the 4th day of agranulocytosis. He was isolated and treated with antibiotics, an antiviral and granulocyte-stimulating growth factor analog (G-CSF). G-CSF was discontinued in 6 days. Both patients had showed their best treatment response on clozapine. After the onset of clozapine-induced agranulocytosis in the second twin, venous blood sample was collected from both patients for DNA extraction. Genotyping results of Affymetrix GeneChip Mapping 250 K SNP Chip revealed a genotype consensus of 96.2% confirming the monozygotic status. In addition, the twin patients were genotyped for MDR1 C3435T and G2677T genetic variants and found to be heterozygotes, i.e. CT and GT, respectively for both C3435T and G2677T polymorphisms. To our knowledge, this is the second report of clozapineinduced agranulocytosis in monozygotic twins. Contrary to the first report [3], our report suggests that the timing of agranulocytosis in monozygotic twins can vary. If a monozygotic twin sibling has a history of clozapine-induced agranulocytosis, the other sibling should not be started on clozapine before zygosity is determined. Our genotyping results also suggest that the existence of both C3435T and G2677T MDR1 polymorphisms might have led to an additive functional loss in P-glycoprotein action, resulting in toxic metabolite accumulation in leukocytes and thus agranulocytosis. Further investigations are necessary to clarify the role of MDR1 allelic variants on development of clozapineinduced agranulocytosis. References [1] Mosyagin, I., Dettling, M., Roots, I., et al., 2004 Impact of myeloperoxidase and NADPH-oxidase polymorphisms in drug-induced agranulocytosis. J Clin Psychopharmacol 24, 613–617. [2] Pauli-Magnus, C., Kroetz, D.L., 2004 Functional implications of genetic polymorphisms in the multidrug resistance gene MDR1 (ABCB1). Pharm Res 21, 904–913. [3] Horacek, J., Libiger, J., Hoschl, C. et al., 2001 Clozapine-induced concordant agranulocytosis in monozygotic twins. Int J Psychiatry Clin Pract 5, 71−73.
P.3.c.059 Oxidative stress status in schizophrenic patients treated with typical versus atypical antipsychotics M. Padurariu1 ° , I. Dobrin1 , C. Stefanescu1 , A. Ciobica2 , R.P. Dobrin1 . 1 Socola Hospital-Gr.T. Popa University of Medicine and Pharmacy, Dept. of Psychiatry, Iasi, Romania; 2 Al. I. Cuza University, Dept. of Biology, Iasi, Romania Introduction: Schizophrenia is a common psychiatric disorder, marked by gross distortion from reality; disturbances in thinking, feeling, and behavior. However, the chemical nature of the schizophrenic brain is still not completely understood.