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P.3.c.061 A review of liver function tests during treatment with a typical antipsychotic drugs: a chart review study
P.3.c Psychotic disorders and antipsychotics – Antipsychotics (clinical) However, haplotypes of ABCB1, as well as the three single SNPs, failed to predict the response to clozapine in the present population of patients. Conclusions: The results of the present study demonstrate that dose-normalized plasma levels of clozapine and its metabolite predict treatment effectiveness, while further studies are warranted to investigate the role of ABCB1. No conflict of interest References [1] Perry PJ, Miller DD, Arndt SV, Cadoret RJ, 1991, Clozapine and norclozapine plasma concentrations and clinical response of treatmentrefractory schizophrenic patients. Am. J. Psychiatry 148(2), 231−5. [2] Wong JO, Leung SP, Mak T, Ng RM, Chan KT, Hon-Kee Cheung H, Choi WK, Lai J, Wai-Kiu Tsang A, 2006, Plasma clozapine levels and clinical response in treatment-refractory Chinese schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 30(2), 251−64. [3] Boulton DW, DeVane CL, Liston HL, Markowitz JS, 2002, In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci 71(2), 163−9.
P.3.c.060 Acute effects of the ampakine farampator on memory and information processing in side effects free elderly volunteers E. Wezenberg1 ° , R.J. Verkes1 , G.S.F. Ruigt2 , W. Hulstijn3 , B.G.C. Sabbe4 . 1 Radboud University Nijmegen Medical Center, Department of Psychiatry, Nijmegen, The Netherlands; 2 NV Organon, Translational Medicine, Oss, The Netherlands; 3 Radboud University Nijmegen, Nijmeegs Institute for Cognition and Information (NICI), Nijmegen, The Netherlands; 4 University of Antwerp, Antwerp Psychiatric Research Institute (CAPRI), Antwerp, Belgium Purpose: Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal longterm potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study further investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. Earlier analyses showed that farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory (Wezenberg et al. 2006). Furthermore, it tended to decrease the number of switching errors in the continuous trail making test (CTMT). Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. It is still unclear, however, whether the drug-placebo effects will show similar positive results for the group of subjects that did not report SEs in both farampator and placebo condition. The results of this analysis will be presented in this poster/paper. Methods: A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (8 male, 8 female; mean age 66.1, sd 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place one hour after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning = VMT, and picture memory = PMT), working and shortterm memory (N-back, symbol recall = SDRT) and motor learning (maze task (3 trials to learn a maze and a 4th trial for a new maze), pursuit rotor). Information processing was assessed with a tangled
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lines task (Tangle), the symbol digit substitution test (SDST) and the CTMT which is considered a executive measure of set-shifting next to information processing. New is that drug-placebo effects were analyzed for the group of 5 subjects (2 male and 3 female; mean 68.60 age, sd 3.21 years) that did not experience SEs in the farampator condition. Results: Farampator (500 mg) significantly improved CTMT performance in the 5 SE free subjects [placebo (p): 35.4 correct and farampator (f): 44.2 correct, t-test: _4.97, p = 0.008]. Mean performance was improved, though not significantly for the SDRT stm (p 2.4, f 4.0, p = 0.17) ltm (p 2.6, f 3.2 p = 0.59) VMT free long term delayed recall (p 7.8, f 8 p = 0.88), PMT1 (p 7.6, f 8.4, p = 0.46), maze task (p 11, 14, 16, 10, f 12, 15, 16, 12 p = 0.48), pursuit (p 11.4 f 12.3 p = 0.34) and SDST (p 43.8, f 45 p = 0.74). Mean performance was decreased for VMT short term delayed recall (p 8.8, f 8 p = 0.1) and PMT2 (p 5.6, f 5 p = 0.47). Conclusions: Although the positive effects on short term memory are no longer significant in this small sample, the mean differences of most memory tests do point towards a positive direction for farampator. The positive results in the CTMT in SE free subjects might be interesting in view of the development of ampakines in the treatment of Alzheimer’s disease and schizophrenia. References [1] Wezenberg E, Verkes RJ, Ruigt GSF, Hulstijn W, Sabbe BGC, 2006, Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. Neuropsychopharmacology. advance online publication, doi: 10.1038/sj.npp.1301257.
P.3.c.061 A review of liver function tests during treatment with a typical antipsychotic drugs: a chart review study N. Atasoy1 ° , A. Erdogan1 , U. Ozturk1 , N. Konuk1 , L. Atik1 , Y. Ustundag2 . 1 Zonguldak Karaelmas University Faculty of Medicine, Psychiatry, Zonguldak, Turkey; 2 Zonguldak Karaelmas University Faculty of Medicine, Gastroenterology, Zonguldak, Turkey Objective: Atypical antipsychotic drugs commonly cause asymptomatic increase in the liver enzyme and serum bilirubin levels however they rarely may induce a serious hepatic toxicity. There is no consensus on the necessity for testing these patients using these drugs for the liver enzyme elevations. This article reports the result of the chart review of hepatic enzymes and serum bilirubin levels of a group of psychiatric patients treated by atypical antipsychotic namely olanzapine, risperidone and quetiapine. Method: Chart reviews were completed on 312 inpatients. The patients whose baseline and follow-up liver function tests including alanine aminotransfeaminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphotase (ALP) and serum bilirubines that were measured before and within the treatment period of first and sixth months were enrolled. Forty eight males and 62 females whose ages ranging from 12−65 years were eligible for this study (no pregnant case was present). Results: The repartition according to treatment is as follows: olanzapine (n = 33), risperidone (n = 29), and quetiapine (n = 48). Two of the 110 patients (1.8%) presented with increased AST levels of up to 4 fold and ALT of thrice the basal level and needed to stop treatment (AST increase in one female with olanzapine
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P.3.c Psychotic disorders and antipsychotics – Antipsychotics (clinical)
20 mg/day; ALT increase in one male with olanzapine 30 mg/day). When the drugs were discontinued, the liver enzyme levels returned to normal in both cases. Thirty one of the 110 patients (28.1%) showed an asymptomatic increase in one or more of the liver enzymes in the first month of this study. An increase in one or more of ALT, AST, GGT, ALP or serum bilirubin levels to greater than the normal ranges was distributed as follows: 30.3% with olanzapine, 27.6% with risperidone, and 27.1% with quetiapine treatments. After 6 months of the treatment with these agents, increased enzyme levels were observed in 27 patients (24.5%). An increase in one or more of these liver emzymes to greater than the normal ranges was distributed as follows: 18.2% with olanzapine, 27.6% with risperidone and 27.1% with quetiapine. Conclusion: There are only a few researches that compare the different atypical antipsychotic drugs with regard to potential hepatotoxicity in the literature. Special care has been advised for these patients. Hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. Our results were in accordance with previous studies that asymptomatic increase of liver enzymes are common but significant liver enzyme elevations are rare during atypical antipsychotic treatment. In the present study, the asymptomatic enzyme elevation patterns of olanzapine, risperidone and quetiapine had almost identical patterns of elevated liver enzymes. These results highlight the need for obtaining baseline liver function tests before atypical antipsychotic therapy and regular monitoring of serum aminotransferase values that had any of risk factors for liver damage during maintenance therapy. References [1] Conley RR, Meltzer HY, 2000, Adverse events related to olanzapine. J Clin Psychiatry 61(8), 26−29. [2] Dumotier G, Cabaret W, Stamatiais L, Saba G, Benadriha R, Rocamora JF, Aubriot-Delmas B, Glikman J, Januel D, 2002, Hepatic tolerance of atypical antipsychotic drugs. Encephale 28(6), 542–551.
P.3.c.062 Understanding needs, interactions, treatment, and expectations: a global survey in schizophrenia and bipolar disorder R.S. McIntyre1 ° , C. O’Brien2 , A.S. Jina2 , L. Chang3 , C. Stave2 . 1 University Health Network, Mood Disorders Psychopharmacology Unit, Toronto, Canada; 2 Pfizer Inc., Global Medical Department, New York, USA; 3 Opinion Research Corporation, Princeton, USA Background: Patients with schizophrenia and bipolar disorder exhibit high rates of medical comorbidity, in particular obesity, diabetes mellitus, and cardiovascular disorders (Harris & Barraclough, 1998; Colton & Manderscheid, 2006; American Diabetes Association et al., 2004). Research describing patients’ and carers’ awareness and knowledge of the medical conditions associated with mental illness and their related interactions with healthcare providers is sparse. Objectives: The purpose of this study (Understanding Needs, Interactions, Treatment, and Expectations [UNITE]) was to examine (a) patient and carer awareness of comorbidities associated with their mental illness; (b) patient and carer knowledge of the long-term health risks associated with mental illness and its treatment; and (c) patient and carer interaction with healthcare providers regarding comorbid conditions.
Methods: To obtain information from a global sample across different systems of healthcare, 5235 subjects, including carers of patients with schizophrenia or bipolar disorder and patients currently receiving pharmacotherapy for schizophrenia or bipolar disorder, were recruited from 11 countries (United States, United Kingdom, France, Italy, Germany, Spain, Sweden, Brazil, South Korea, Australia, and Greece). All participants completed a 35to 40-minute survey. Results: Based on self-reports of weight and height, body mass index (BMI) computations revealed that 33% of patients with schizophrenia and 35% of patients with bipolar disorder were obese (BMI > 30 kg/m2 ). 60% of patients with schizophrenia and 62% of patients with bipolar disorder reported a weight gain that exceeded 7% of their preillness body weight. Carers’ reports yielded similar findings. About two thirds of both patients and carers attributed weight gain to psychiatric medication. Patients reported additional health problems caused by or worsened by weight gain. Increased cholesterol levels were reported by 41% of patients with schizophrenia and 35% of patients with bipolar disorder. High blood pressure was reported by 31% of patients with schizophrenia and 29% of patients with bipolar disorder. Diabetes was reported by 27% of patients with schizophrenia and 17% of patients with bipolar disorder. Compared with patients, carers reported slightly greater percentages of patients with additional health problems associated with weight gain. Healthcare providers discussed potential long-term consequences of weight gain with 53% of patients with schizophrenia and 50% of patients with bipolar disorder, and they discussed the impact of psychotropic medication on comorbidities with 59% of patients with schizophrenia and 51% of patients with bipolar disorder. However, only 22% of patients with schizophrenia and 20% with bipolar disorder reported receiving a physical examination, 32% and 28%, respectively, reported being weighed, and 34% and 43%, respectively, reported having a blood test related to the diagnosis or assessment of a comorbid medical disorder. Satisfaction with psychiatric care among patients and carers was not related to weight gain. Conclusions: These results suggest that patients are suboptimally informed about issues surrounding medical comorbidity and the long-term consequences despite high reported rates of medical comorbidity. Carer responses generally matched patient responses. Systematic application of health promotion and screening is still lacking in this vulnerable patient population. This study was supported by Pfizer Inc. References [1] American Diabetes Association American Psychiatric Association American Association of Clinical Endocrinologists North American Association for the Study of Obesity, 2004, Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry 65, 267–272. [2] Colton CW, Manderscheid RW, 2006, Congruencies in increased mortality rates, years of potential life lost, and causes of death among public mental health clients in eight states. Prev Chronic Dis 3, A42. [3] Harris EC, Barraclough B, 1998, Excess mortality of mental disorder. Br J Psychiatry 173, 11−53.
P.3.c.060 Acute effects of the ampakine farampator on memory and information processing in side effects free elderly volunteers E. Wezenberg1 ° , R.J. Verkes1 , G.S.F. Ruigt2 , W. Hulstijn3 , B.G.C. Sabbe4 . 1 Radboud University Nijmegen Medical Center, Department of Psychiatry, Nijmegen, The Netherlands; 2 NV Organon, Translational Medicine, Oss, The Netherlands; 3 Radboud University Nijmegen, Nijmeegs Institute for Cognition and Information (NICI), Nijmegen, The Netherlands; 4 University of Antwerp, Antwerp Psychiatric Research Institute (CAPRI), Antwerp, Belgium Purpose: Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal longterm potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study further investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. Earlier analyses showed that farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory (Wezenberg et al. 2006). Furthermore, it tended to decrease the number of switching errors in the continuous trail making test (CTMT). Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. It is still unclear, however, whether the drug-placebo effects will show similar positive results for the group of subjects that did not report SEs in both farampator and placebo condition. The results of this analysis will be presented in this poster/paper. Methods: A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (8 male, 8 female; mean age 66.1, sd 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place one hour after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning = VMT, and picture memory = PMT), working and shortterm memory (N-back, symbol recall = SDRT) and motor learning (maze task (3 trials to learn a maze and a 4th trial for a new maze), pursuit rotor). Information processing was assessed with a tangled
S459
lines task (Tangle), the symbol digit substitution test (SDST) and the CTMT which is considered a executive measure of set-shifting next to information processing. New is that drug-placebo effects were analyzed for the group of 5 subjects (2 male and 3 female; mean 68.60 age, sd 3.21 years) that did not experience SEs in the farampator condition. Results: Farampator (500 mg) significantly improved CTMT performance in the 5 SE free subjects [placebo (p): 35.4 correct and farampator (f): 44.2 correct, t-test: _4.97, p = 0.008]. Mean performance was improved, though not significantly for the SDRT stm (p 2.4, f 4.0, p = 0.17) ltm (p 2.6, f 3.2 p = 0.59) VMT free long term delayed recall (p 7.8, f 8 p = 0.88), PMT1 (p 7.6, f 8.4, p = 0.46), maze task (p 11, 14, 16, 10, f 12, 15, 16, 12 p = 0.48), pursuit (p 11.4 f 12.3 p = 0.34) and SDST (p 43.8, f 45 p = 0.74). Mean performance was decreased for VMT short term delayed recall (p 8.8, f 8 p = 0.1) and PMT2 (p 5.6, f 5 p = 0.47). Conclusions: Although the positive effects on short term memory are no longer significant in this small sample, the mean differences of most memory tests do point towards a positive direction for farampator. The positive results in the CTMT in SE free subjects might be interesting in view of the development of ampakines in the treatment of Alzheimer’s disease and schizophrenia. References [1] Wezenberg E, Verkes RJ, Ruigt GSF, Hulstijn W, Sabbe BGC, 2006, Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. Neuropsychopharmacology. advance online publication, doi: 10.1038/sj.npp.1301257.
P.3.c.061 A review of liver function tests during treatment with a typical antipsychotic drugs: a chart review study N. Atasoy1 ° , A. Erdogan1 , U. Ozturk1 , N. Konuk1 , L. Atik1 , Y. Ustundag2 . 1 Zonguldak Karaelmas University Faculty of Medicine, Psychiatry, Zonguldak, Turkey; 2 Zonguldak Karaelmas University Faculty of Medicine, Gastroenterology, Zonguldak, Turkey Objective: Atypical antipsychotic drugs commonly cause asymptomatic increase in the liver enzyme and serum bilirubin levels however they rarely may induce a serious hepatic toxicity. There is no consensus on the necessity for testing these patients using these drugs for the liver enzyme elevations. This article reports the result of the chart review of hepatic enzymes and serum bilirubin levels of a group of psychiatric patients treated by atypical antipsychotic namely olanzapine, risperidone and quetiapine. Method: Chart reviews were completed on 312 inpatients. The patients whose baseline and follow-up liver function tests including alanine aminotransfeaminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphotase (ALP) and serum bilirubines that were measured before and within the treatment period of first and sixth months were enrolled. Forty eight males and 62 females whose ages ranging from 12−65 years were eligible for this study (no pregnant case was present). Results: The repartition according to treatment is as follows: olanzapine (n = 33), risperidone (n = 29), and quetiapine (n = 48). Two of the 110 patients (1.8%) presented with increased AST levels of up to 4 fold and ALT of thrice the basal level and needed to stop treatment (AST increase in one female with olanzapine
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P.3.c Psychotic disorders and antipsychotics – Antipsychotics (clinical)
20 mg/day; ALT increase in one male with olanzapine 30 mg/day). When the drugs were discontinued, the liver enzyme levels returned to normal in both cases. Thirty one of the 110 patients (28.1%) showed an asymptomatic increase in one or more of the liver enzymes in the first month of this study. An increase in one or more of ALT, AST, GGT, ALP or serum bilirubin levels to greater than the normal ranges was distributed as follows: 30.3% with olanzapine, 27.6% with risperidone, and 27.1% with quetiapine treatments. After 6 months of the treatment with these agents, increased enzyme levels were observed in 27 patients (24.5%). An increase in one or more of these liver emzymes to greater than the normal ranges was distributed as follows: 18.2% with olanzapine, 27.6% with risperidone and 27.1% with quetiapine. Conclusion: There are only a few researches that compare the different atypical antipsychotic drugs with regard to potential hepatotoxicity in the literature. Special care has been advised for these patients. Hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. Our results were in accordance with previous studies that asymptomatic increase of liver enzymes are common but significant liver enzyme elevations are rare during atypical antipsychotic treatment. In the present study, the asymptomatic enzyme elevation patterns of olanzapine, risperidone and quetiapine had almost identical patterns of elevated liver enzymes. These results highlight the need for obtaining baseline liver function tests before atypical antipsychotic therapy and regular monitoring of serum aminotransferase values that had any of risk factors for liver damage during maintenance therapy. References [1] Conley RR, Meltzer HY, 2000, Adverse events related to olanzapine. J Clin Psychiatry 61(8), 26−29. [2] Dumotier G, Cabaret W, Stamatiais L, Saba G, Benadriha R, Rocamora JF, Aubriot-Delmas B, Glikman J, Januel D, 2002, Hepatic tolerance of atypical antipsychotic drugs. Encephale 28(6), 542–551.
P.3.c.062 Understanding needs, interactions, treatment, and expectations: a global survey in schizophrenia and bipolar disorder R.S. McIntyre1 ° , C. O’Brien2 , A.S. Jina2 , L. Chang3 , C. Stave2 . 1 University Health Network, Mood Disorders Psychopharmacology Unit, Toronto, Canada; 2 Pfizer Inc., Global Medical Department, New York, USA; 3 Opinion Research Corporation, Princeton, USA Background: Patients with schizophrenia and bipolar disorder exhibit high rates of medical comorbidity, in particular obesity, diabetes mellitus, and cardiovascular disorders (Harris & Barraclough, 1998; Colton & Manderscheid, 2006; American Diabetes Association et al., 2004). Research describing patients’ and carers’ awareness and knowledge of the medical conditions associated with mental illness and their related interactions with healthcare providers is sparse. Objectives: The purpose of this study (Understanding Needs, Interactions, Treatment, and Expectations [UNITE]) was to examine (a) patient and carer awareness of comorbidities associated with their mental illness; (b) patient and carer knowledge of the long-term health risks associated with mental illness and its treatment; and (c) patient and carer interaction with healthcare providers regarding comorbid conditions.
Methods: To obtain information from a global sample across different systems of healthcare, 5235 subjects, including carers of patients with schizophrenia or bipolar disorder and patients currently receiving pharmacotherapy for schizophrenia or bipolar disorder, were recruited from 11 countries (United States, United Kingdom, France, Italy, Germany, Spain, Sweden, Brazil, South Korea, Australia, and Greece). All participants completed a 35to 40-minute survey. Results: Based on self-reports of weight and height, body mass index (BMI) computations revealed that 33% of patients with schizophrenia and 35% of patients with bipolar disorder were obese (BMI > 30 kg/m2 ). 60% of patients with schizophrenia and 62% of patients with bipolar disorder reported a weight gain that exceeded 7% of their preillness body weight. Carers’ reports yielded similar findings. About two thirds of both patients and carers attributed weight gain to psychiatric medication. Patients reported additional health problems caused by or worsened by weight gain. Increased cholesterol levels were reported by 41% of patients with schizophrenia and 35% of patients with bipolar disorder. High blood pressure was reported by 31% of patients with schizophrenia and 29% of patients with bipolar disorder. Diabetes was reported by 27% of patients with schizophrenia and 17% of patients with bipolar disorder. Compared with patients, carers reported slightly greater percentages of patients with additional health problems associated with weight gain. Healthcare providers discussed potential long-term consequences of weight gain with 53% of patients with schizophrenia and 50% of patients with bipolar disorder, and they discussed the impact of psychotropic medication on comorbidities with 59% of patients with schizophrenia and 51% of patients with bipolar disorder. However, only 22% of patients with schizophrenia and 20% with bipolar disorder reported receiving a physical examination, 32% and 28%, respectively, reported being weighed, and 34% and 43%, respectively, reported having a blood test related to the diagnosis or assessment of a comorbid medical disorder. Satisfaction with psychiatric care among patients and carers was not related to weight gain. Conclusions: These results suggest that patients are suboptimally informed about issues surrounding medical comorbidity and the long-term consequences despite high reported rates of medical comorbidity. Carer responses generally matched patient responses. Systematic application of health promotion and screening is still lacking in this vulnerable patient population. This study was supported by Pfizer Inc. References [1] American Diabetes Association American Psychiatric Association American Association of Clinical Endocrinologists North American Association for the Study of Obesity, 2004, Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry 65, 267–272. [2] Colton CW, Manderscheid RW, 2006, Congruencies in increased mortality rates, years of potential life lost, and causes of death among public mental health clients in eight states. Prev Chronic Dis 3, A42. [3] Harris EC, Barraclough B, 1998, Excess mortality of mental disorder. Br J Psychiatry 173, 11−53.