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P.3.d.002 The changes of plasma monoamine metabolites levels after antipsychotic drug treatment in patients with schizophrenia
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P.3.d Psychotic disorders and antipsychotics – Antipsychotics (basic)
were shifted to the right in a parallel manner in the presence of higher dopamine concentration. The antagonist activities of these antipsychotics were less potent than those in hD2S -Low cells treated with the equal 1 mM dopamine concentration. In contrast, aripiprazole did not antagonize the dopamine response and acted as an agonist. Conclusion: The presented data suggests a unique receptorreserve dependent antagonist property of aripiprazole that is totally different from those of other antipsychotics. This may account for the clinical findings that aripiprazole treatment results in improvement in positive and negative symptoms of schizophrenia. It may also explain aripiprazole’s low propensity for induction of EPS and hyperprolactinemia. The antagonist potencies of other antipsychotics depend on the variation in receptor reserve and dopamine concentrations. The antagonist properties for other antipsychotics, particularly clozapine and quetiapine, may account for the clinical benefit and low propensity for EPS and hyperprolactinemia seen with lower doses of these antipsychotics. References [1] Tadori Y, Miwa T, Tottori K, Burris KD, Stark A, Mori T, et al, 2005, Aripiprazole’s low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic. Eur J Pharmacol 515, 10−19.
P.3.d.002 The changes of plasma monoamine metabolites levels after antipsychotic drug treatment in patients with schizophrenia C.Y. Jeong1 ° , J.G. Lee1 , Y.H. Jin2 . 1 Dong Seo Mental Hospital, Psychiatry, Masan, South-Korea; 2 Changwon Fatima Hospital, Psychiatry, Changwon, South-Korea Purpose: Many investigators are trying to find out the significant roles of biogenic monoamine neurotransmitters in the etiopathogenesis of schizophrenic illness. Dopamine has been the crucial neuro-transmitter in schizophrenic research. Since the advent of atypical antipsychotics, other neurotransmitters including serotonin became of interest. And also it is well known of different neurotransmitter activities in the positive and negative type of schizophrenia. The author assayed three metabolites of monoamine neurotransmitters and the potentiality of plasma 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations as biological markers was analyzed. And then the author compared the levels before and after neuroleptic treatment (haloperidol and risperidone respectively). Methods: Forty male subjects with schizophrenia were enrolled in this study. Haloperidol group (Dongseo hospital, Masan, Kyungnam) was comprised of 19 subjects and risperidone group (Woorideul hospital, Hadong, Kyungnam) 21 subjects. Haloperidol and risperidone were administered for 6 weeks. First baseline plasma was obtained at 8:00 AM in neuroleptic naive state. Single dose of neuroleptics (haloperidol 5 mg, risperidone 2 mg) was administered to find out the acute changes of monoamine neurotransmitter systems. Consecutive samplings were done at 2, 4, and 6 week point after neuroleptic treatment. The 5-HIAA, HVA and MHPG levels were assayed using high pressure liquid chromatography-electrochemical detection method. The difference between HVA level and corrected MHPG level was approximated as central dopaminergic index (CDI). Results: The plasma levels of MHPG (p < 0.0125) and HVA(p < 0.0125) was increased significantly after single dose of
neuroleptics treatment. The CDI levels showed profound increment after single dose of neuroleptics treatment (p < 0.0125). The CDI was increased by 8% in haloperidol group and by 68% in risperidone group. Conclusions: These findings suggest that catecholaminergic systems change drastically after single dose of neuroleptic treatment, particularly in dopaminergic system. The differences of CDI between haloperidol group and risperidone group can be explained by the different influences on serotonergic system between typical and atypical neuroleptics. The plasma 5-HIAA, HVA and MHPG levels can be used as biological markers in research for schizophrenic illness. Schizophrenia can be subgrouped by different activities of serotonin, dopamine and norepinephrine. Plasma 5-HIAA, HVA, MHPG and CDI levels at baseline and after single dose treatment (n = 40, ng/ml, Mean±SD)
5-HIAA Total subjects Haloperidol group Risperidone group MHPG Total subjects Haloperidol group Risperidone group HVA Total subjects Haloperidol group Risperidone group CDIc Total subjects Haloperidol group Risperidone group
Baselinea
Single doseb
6.08±1.87 5.88±1.86 6.25±1.82
6.01±1.87 5.85±1.87 6.15±1.92
5.35±1.96 5.56±2.24 5.16±1.71
5.99±1.97a 5.98±1.52 5.99±2.33a
9.20±3.90 8.88±2.63 9.48±4.82
10.84±4.49a 9.93±3.89 11.62±4.92a
5.59±2.74 6.11±2.35 5.12±3.03
7.84±4.22a 6.93±3.63 8.62±4.61d
a
Baseline sampling was obtained at 8 AM after 2week neuroleptic washout. Single dose of neuroleptics was administered after baseline sampling. Sampling was done 24 hours later. c CDI, central dopaminergic index derived from difference between HVA and corrected MHPG concentration. d Significant increase after single dose administration (Friedman test, multiple comparisons by Wilcoxon signed ranks test, Bonferroni correction, p < 0.0125). b
References [1] Amin F, Davidson M, Kahn RS, Schmeidler J, Stern R, Knott PJ, Apter S, 1995, Assessment of the central dopaminergic index of plasma HVA in schizophrenia. Schizophr Bull 21, 53−66. [2] Angelopoulos EK, Markianos M, Daskalopoulos EG, Hatzimanolis J, Tzemos J, 2002, Changes in central serotonergic function as a correlate of duration of illness in paranoid schizophrenia. Psychiatry Res 110, 9−17. [3] Aymard N, Viala A, Clement M-N, Jacquot M, Vacheron M-N, Gauillard J, Caroli F, 2002, Long-term pharmacoclinical follow-up in schizophrenic patients treated with risperidone. Prog Neuro-Psychopharmacol Biol Psychiatry 26, 975–988.
P.3.d.003 Antipsychotic prescription patterns among psychiatrists at state hospital in Turkey O. Karamustafalioglu ° , B. Ozcelik, S. Gonenli, B. Bakim, Y. Ceylan Cengiz. Sisli Etfal Teaching and Research Hospital, Psychiatry, Istanbul, Turkey Introduction: Many studies suggested variables that affect clinician to choosing antipsychotics (eg. patients age, etnicity, socioe-
P.3.d Psychotic disorders and antipsychotics – Antipsychotics (basic)
were shifted to the right in a parallel manner in the presence of higher dopamine concentration. The antagonist activities of these antipsychotics were less potent than those in hD2S -Low cells treated with the equal 1 mM dopamine concentration. In contrast, aripiprazole did not antagonize the dopamine response and acted as an agonist. Conclusion: The presented data suggests a unique receptorreserve dependent antagonist property of aripiprazole that is totally different from those of other antipsychotics. This may account for the clinical findings that aripiprazole treatment results in improvement in positive and negative symptoms of schizophrenia. It may also explain aripiprazole’s low propensity for induction of EPS and hyperprolactinemia. The antagonist potencies of other antipsychotics depend on the variation in receptor reserve and dopamine concentrations. The antagonist properties for other antipsychotics, particularly clozapine and quetiapine, may account for the clinical benefit and low propensity for EPS and hyperprolactinemia seen with lower doses of these antipsychotics. References [1] Tadori Y, Miwa T, Tottori K, Burris KD, Stark A, Mori T, et al, 2005, Aripiprazole’s low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic. Eur J Pharmacol 515, 10−19.
P.3.d.002 The changes of plasma monoamine metabolites levels after antipsychotic drug treatment in patients with schizophrenia C.Y. Jeong1 ° , J.G. Lee1 , Y.H. Jin2 . 1 Dong Seo Mental Hospital, Psychiatry, Masan, South-Korea; 2 Changwon Fatima Hospital, Psychiatry, Changwon, South-Korea Purpose: Many investigators are trying to find out the significant roles of biogenic monoamine neurotransmitters in the etiopathogenesis of schizophrenic illness. Dopamine has been the crucial neuro-transmitter in schizophrenic research. Since the advent of atypical antipsychotics, other neurotransmitters including serotonin became of interest. And also it is well known of different neurotransmitter activities in the positive and negative type of schizophrenia. The author assayed three metabolites of monoamine neurotransmitters and the potentiality of plasma 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations as biological markers was analyzed. And then the author compared the levels before and after neuroleptic treatment (haloperidol and risperidone respectively). Methods: Forty male subjects with schizophrenia were enrolled in this study. Haloperidol group (Dongseo hospital, Masan, Kyungnam) was comprised of 19 subjects and risperidone group (Woorideul hospital, Hadong, Kyungnam) 21 subjects. Haloperidol and risperidone were administered for 6 weeks. First baseline plasma was obtained at 8:00 AM in neuroleptic naive state. Single dose of neuroleptics (haloperidol 5 mg, risperidone 2 mg) was administered to find out the acute changes of monoamine neurotransmitter systems. Consecutive samplings were done at 2, 4, and 6 week point after neuroleptic treatment. The 5-HIAA, HVA and MHPG levels were assayed using high pressure liquid chromatography-electrochemical detection method. The difference between HVA level and corrected MHPG level was approximated as central dopaminergic index (CDI). Results: The plasma levels of MHPG (p < 0.0125) and HVA(p < 0.0125) was increased significantly after single dose of
neuroleptics treatment. The CDI levels showed profound increment after single dose of neuroleptics treatment (p < 0.0125). The CDI was increased by 8% in haloperidol group and by 68% in risperidone group. Conclusions: These findings suggest that catecholaminergic systems change drastically after single dose of neuroleptic treatment, particularly in dopaminergic system. The differences of CDI between haloperidol group and risperidone group can be explained by the different influences on serotonergic system between typical and atypical neuroleptics. The plasma 5-HIAA, HVA and MHPG levels can be used as biological markers in research for schizophrenic illness. Schizophrenia can be subgrouped by different activities of serotonin, dopamine and norepinephrine. Plasma 5-HIAA, HVA, MHPG and CDI levels at baseline and after single dose treatment (n = 40, ng/ml, Mean±SD)
5-HIAA Total subjects Haloperidol group Risperidone group MHPG Total subjects Haloperidol group Risperidone group HVA Total subjects Haloperidol group Risperidone group CDIc Total subjects Haloperidol group Risperidone group
Baselinea
Single doseb
6.08±1.87 5.88±1.86 6.25±1.82
6.01±1.87 5.85±1.87 6.15±1.92
5.35±1.96 5.56±2.24 5.16±1.71
5.99±1.97a 5.98±1.52 5.99±2.33a
9.20±3.90 8.88±2.63 9.48±4.82
10.84±4.49a 9.93±3.89 11.62±4.92a
5.59±2.74 6.11±2.35 5.12±3.03
7.84±4.22a 6.93±3.63 8.62±4.61d
a
Baseline sampling was obtained at 8 AM after 2week neuroleptic washout. Single dose of neuroleptics was administered after baseline sampling. Sampling was done 24 hours later. c CDI, central dopaminergic index derived from difference between HVA and corrected MHPG concentration. d Significant increase after single dose administration (Friedman test, multiple comparisons by Wilcoxon signed ranks test, Bonferroni correction, p < 0.0125). b
References [1] Amin F, Davidson M, Kahn RS, Schmeidler J, Stern R, Knott PJ, Apter S, 1995, Assessment of the central dopaminergic index of plasma HVA in schizophrenia. Schizophr Bull 21, 53−66. [2] Angelopoulos EK, Markianos M, Daskalopoulos EG, Hatzimanolis J, Tzemos J, 2002, Changes in central serotonergic function as a correlate of duration of illness in paranoid schizophrenia. Psychiatry Res 110, 9−17. [3] Aymard N, Viala A, Clement M-N, Jacquot M, Vacheron M-N, Gauillard J, Caroli F, 2002, Long-term pharmacoclinical follow-up in schizophrenic patients treated with risperidone. Prog Neuro-Psychopharmacol Biol Psychiatry 26, 975–988.
P.3.d.003 Antipsychotic prescription patterns among psychiatrists at state hospital in Turkey O. Karamustafalioglu ° , B. Ozcelik, S. Gonenli, B. Bakim, Y. Ceylan Cengiz. Sisli Etfal Teaching and Research Hospital, Psychiatry, Istanbul, Turkey Introduction: Many studies suggested variables that affect clinician to choosing antipsychotics (eg. patients age, etnicity, socioe-