- Email: [email protected]
P.3.084 Effect of antipsychotics on low serum brain derived neurotrophic factor levels in schizophrenia
P3 Psychotic disorders and antipsychotics than 5 years. We analyzed the age, sex and weight of our subjects, the type, duration and dosage of the medication prescribed, and the side effects according to the UKU side effect rating scale. Results: The total number of subjects was 87 (48 male, 39 female) and the mean age was 49.2±8.3 years old. The mean time of medication was 8.7±2.6 years. Among the methods of administration, combination of haloperidol and chlorpromazine was applied for 30 patients the most number (34.5%), single haloperidol for 19 patients (21.8%), combination of haloperidol and antipsychotics other than chlorpromazine for 30 patients (34.5%), and single use of other antipsychotics other than haloperidol for 8 patients (9.2%). The mean amount used for treatment of haloperidol was found to be 10.5±9.9mg/day. Psychic side effects clarified based on UKU were asthenia/lassitude/increased fatigability in 12 (13.8%), sleepiness/sedation in 23 (26.4%), failing memory in 7 (8.0%), depression in 4 (4.6%), tension/inner unrest in 6 (6.9%), reduced duration of sleep in 3 (3.4%), and emotional indifference in 77 (88.5%). Neurologic side effects were rigidity in 39 patients (44.8%), hypokinesia/akinesia in 73 (83.9%), hyperkinesia logic in 56 (64.4%), tremor in 27 (31.0%), and akathisia in 5 (5.7%). Autonomic side effects were reduced salivation in 41 (47.1%), nausea/vomiting in 3 (3.4%), constipation in 10 (11.5%), and orthostatic dizziness in 12 (13.8%). Other side effects were pruritus in 11 (12.6%), weight gain in 19 (21.8%), weight loss in 34 (39.1%), amenorrhea in 2 (5.1%), galactorrhea in 14 (16.1%), headache in 8 (9.2%). Conclusion: Various side effects were found to be induced by typical antipsychotics and among them neurologic side effects were in the greatest number. It is speculated that the long term use of high potency antipsychotics might contribute to the result. More investigation on coginition involved and somatic side effects will be needed in the near future.
References [1] Schizophr Res. 1991 Mar-Apt; 4(2): 81 90. Related Articles, Links Drug treatment of schizophrenia. Overview of recent research. Marder SR, Wirshing WC, Van Putten T.
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Subjective experience and dopamine D2 receptor occupancy in patients treated with antipsychotics: clinical implications
L. De Haan*. AMC, Psychiatty, Amsterdam, The Netherlands Objectives: This (poster) presentation gives an overview of two studies of our group on the association between dopaminergic neurotransmission and the subjective experience of patients with schizophrenia. Methods: 1. Patients' subjective experience was measured with the Subjective Well-being under Neuroleptic treatment scale (SWN) after a stable dose period of at least 6 weeks of olanzapine, risperidone or haloperidol. To determine the levels of striatal D2 receptor occupancy, [123I]IBZM SPECT imaging was performed. 2. We sought to identify which aspects of subjective wellbeing are most strongly related to dopamine D2 receptor occupancy. Results: 1. Higher striatal D2 receptor occupancy by typical and atypical antipsychotics is related to worse subjective experience, more severe negative symptoms, and depression. Individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergicblocking drugs. There is preliminary evidence that a window of
$491
striatal D2 receptor occupancy between 60% and 70% is optimal for the subjective experience of patients. These occupancies are often reached even with low dosages of antipsychotic drugs. 2. Monitoring feelings of comfort, self-confidence, and safety may guide clinicians and researchers to find the optimal dopamine D2 receptor occupancy. Conclusions: Dopaminergic neurotransmission is relevant for subjective experience. Reaching an optimal dopamine D2 receptor occupancy is clinically relevant, since subjective experience associated with antipsychotic medication is related to medication compliance. Antipsychotic drug dosages often need to be lower than levels in common use.
•
Effect of antipsychotics on low serum brain derived neurotrophic factor levels in schizophrenia
S. Pirildar 1 *, A.S. Gonul 1, F. Taneli 2, F. Akdeniz 1 . ]Ege
University, Psychiatty, Izm#; Turkey; 2Celal Bayar University, Biochemistty, Turkey There is a line of evidence that disruption of neurotrophins could play a role in the etiology of schizophrenia and antipsychotics show their effect by altering levels of neurotrophins. In the present study, we aimed to determine serum BDNF levels between untretaed schizophrenia patients and healthy subjects and the effect of antipsychotics on serum BDNF levels in patients with schizophrenia. Twenty-two schizophrenia patients who didn't take any psychotropic drugs at least for a period of two weeks were enrolled. The mean age of the patients was 27.81±9.54 years (range: 17 47 years). Their mean age at onset of psychosis was 24.36±3.07 years and mean duration of illness was 15.2±13.04 months (range: 6 82 months). The control group consisted of 22 age (7 male, 15 female), and sex-matched physically and mentally healthy subjects who volunteered to participate in the study. Exclusion criteria: having any other physical illness, organic brain disorder, alcohol and/or drug abuse and being pregnant. PANSS scale was used to analyze the positive and negative symptoms and blood samples were collected at baseline and after six weeks of treatment period. Blood samples were collected from the control group, as well. Seventeen patients received risperidone (mean dose 4 m g daily), two received clozapine (mean dose 4 5 0 m g daily) and the remaining three received olanzapine (mean dose 25 mg daily). Wilcoxon signed ranks test was applied for comparisons between baseline and post-treatment serum BDNF levels of patients. Mann Whitney U test was used for comparison serum BDNF levels of patients and control group. Relationship of BDNF levels with PANSS scores were assessed by means of spearman correlations. The baseline serum BDNF levels of patients were lower than controls' (t 4.56; d.f. 21, p<0.001). After 6 weeks of antipsychotic treatment, positive scores (t 7.0; d.f. 21, p < 0.001), negative scores (t 7.4; d.f. 21, p < 0 . 0 0 1 ) and general psychopathology scores (t 20.9; d.f. 27, p <0.001) for PANSS decreased significantly. There was no statistically significance between pre- and post-treatment BDNF levels (p > 0.05). The major finding of this study was that serum BDNF levels of untreated schizophrenia patients were significantly lower than the healthy controls' suggesting that BDNF would be implicated in some neurodevelopmental aspects of schizophrenia. We didn't detect any alteration in serum BDNF levels of the schizophrenia patients after antipsychotic treatment. Shimizu et al (2003) reported that antipsychotic treatment would not change serum BDNF levels in schizophrenia patients.
P3 Psychotic disorders and antipsychotics
$492
References [1] Durany, N., Michel, T., Zochling, R., Boissl, K.W., Cruz-Sanchez, F.F., Riederer, R, Thome, J., 2001. Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses, SchizophL:Res. 52, 79 86. [2] Toyooka, K. Asama, K. Watanabe, Y., Mtu'atake, T., Takahashi, M., Someya, T., Nawa, H., 2002. Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients, Psychiatry Res. 110, 24~257. [3] Shimizu, E., Hashimato, K. Watanabe, H., Komatsu, N., Okamura, N., Koike, K., Shinado, N., Nakazato, M., Kumakiri, N., Okada, S.O., Iyo, M., 2003. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia are indistinguishable from controls, Neurosci. Letters 351, 1114.
•
Serum brain derived neurotrophic factor levels in schizophrenic patients treated with olanzapine and clozapine
our results support the hypothesis of our study BDNF remains as an interesting molecule for further detailed research to evaluate the effect of BDNF in the pathogenesis of schizophrenia.
References [1] Durany, N., Michel, T., Zochling, R., Boissl, K.W., Cruz-Sanchez, F.F., Riederer, R, Thome, J., 2001. Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses, Schizophr. Res. 52, 79 86. [2] Fourney, J.C., Ashe, P., Nylen, K., Juorio, A.V., Li, X.M., 2002. Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration, Brain Res. 954, 11 20. [3] Pirildar, S., G6nfil, A.S., Taneli, E, Akdeniz, E, 2004. Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment. Prog Neuropsychopharmacol Biol Psychiatry. Jul; 28(4): 709 13.
•
Comparison between responders and nonresponders in first-episode schizophrenia
S. Pirildar 1 *, F. Taneli 2, L. Mete 3, A.S. Gonul 1, O. Kucuk 1, N. Zorlu 1 . ]Ege University, Psychiatty, Izmir, Turkey; 2Celal
E. Ceskova*, R.R Prikryl, T.K. Kasparek, H.K. Kucerova.
Bayar University, Biochemistty, Turkey; 3Ataturk Education and Training Hospital, Psychiatty, Turkey
Masmyk University, Department of Psychiatty, Brno, Czech Republic
Several studies indicate that neurotropins have a role in the etiology and treatment of schizophrenia. It is suggested that antipsychotics improve the symptoms of schizophrenia ~except altering neurotransmitters- via regulation of genes involving remodeling and survival of adult neurons and neurotrophins. The aim of the study is to investigate the effect of clozapine and olanzapine on serum BDNF levels in patinets with schizophrenia. Fifty-five patients with schizophrenia using olanzapine or clozapine at least for 6 months were enrolled into the study. The control group was consisted of schizophrenia patients who didn't use any psychotropic drugs at least for 2 weeks. Their mean age was for olanzapine group (34.50±10.04); clozapine group (29.15±6.89); control group (27.79±8.99) years. The duration of their illness was for olanzapine group (73.50±80.32); clozapine group (74.25±36.55) control group (25.83±30.36) month. In our analyzes we used the PANNS scale to evaluate the positive and negative symptoms. Blood samples were collected for each patient at the index admission to evaluate serum BDNF levels. The exclusion criteria: using any other psychotropics, having organic brain disorder, alcohol or drug abuse, pregnancy, or any physical illness. Results: PANSS scores were (general. positive, negative) 27.65±14.20; 14.85±10.39; 17.75±7.97 in clozapine group; 21.25±5.59; 10.25±2.49; 13.33±5.21 in olanzapine group and 57.70±10.66; 32.58±0.05; 30.04±7.03 in drug-free patients. Serum BDNF level of clozapine group was 16.27±2.45; of olanzapine group 21.91±6.07 and of drug-free patients 14.19±8.12 Using ANOVA we detected higher serum BDNF levels of patients treated with clozapine and olanzapine than drug-free patients (df 2; f 4.920; p 0.01). There was a positive correlation between positive PANSS scores and BDNF levels (p 0.027; t 0.263) using pearson correlation test. In this study we detect high serum BDNF levels after treatment with clozapine and olanzapine than the drug-free schizophrenic patients. In our previous study we did not found any alteration in serum BDNF levels after six weeks of antipsychotic treatment. In that study 15 of 22 received risperidone for a period of six weeks. It is reported that antipsychotics with powerful D2 receptor antagonism properties like haloperidol significantly decreased hippocampal BDNF mRNA in the CA1. BDNF is upregulated by antipsychotic treatments with 5HT2A receptor blockade properties. Although
Purposes of the study: 1) to assess in details the psychopathology before and after the acute antipsychotic treatment, 2) to compare responders and nonresponders. Methods used: Male patients consecutively (November 1997 to March 2004) hospitalised with first-episode schizophrenia (according to ICD 10) were included. Clinical assessment was performed using the Positive and Negative Syndrome Scale (PANSS) after admission (before treatment) and at discharge. The response rate (defined as minimally 30% reduction from baseline in the PANSS total score) was evaluated at discharge. After a baseline assessment all patients were treated openly by monotherapy with an antipsychotic, the doses were inidividualised. The statistical analysis was made by means of the t-test (the Wilcoxon matched-pairs test and testing for differences between means). Results: The study included 104 inpatients. Their average age was 23.3 (SD 5.7) years, the mean duration of the hospitalisation 44.5 (15.3) days and the mean length of illness, determined from the time the patients first exhibited illness-related behavioural symptoms 0.77 (1.0) years. 28 patients were treated with classical antipsychotics, 64 patients with risperidone, 12 patients with others 2nd generation antipsychotics. Scores for all symptoms decreased significantly before discharge, in average 44 days after admission. The negative symptoms improved less, compared to the positive ones. On admission in the total sample the most frequently observed symptoms were lack of judgement and insight (in 87.6% of patients), suspiciousness/feelings of persecution (82%), delusions (77%). Individual negative symptoms were present in about one half of the patients. At discharge the most frequent symptoms were again lack of judgement and insight (55.7%) and blunted affect (22%). We identified 76 responders (73%). On admission, responders compared with nonresponders had significantly higher scores on the total and all the subscales of PANSS and significantly higher scores of 21 individual items out of 30 items. On the contrary, at discharge the responders compared with nonresponders had significantly lower scores on the total and all subscales of PANSS and significantly lower psychopathology in 25 out of 30 items of individual symptoms. In nonresponders no decrease of the negative subscale of PANSS was found during the treatment. The means score of some negative symptoms mildly increased (blunted affect, lack of spontaneity). The most striking difference between responders and noresponders
References [1] Schizophr Res. 1991 Mar-Apt; 4(2): 81 90. Related Articles, Links Drug treatment of schizophrenia. Overview of recent research. Marder SR, Wirshing WC, Van Putten T.
•
Subjective experience and dopamine D2 receptor occupancy in patients treated with antipsychotics: clinical implications
L. De Haan*. AMC, Psychiatty, Amsterdam, The Netherlands Objectives: This (poster) presentation gives an overview of two studies of our group on the association between dopaminergic neurotransmission and the subjective experience of patients with schizophrenia. Methods: 1. Patients' subjective experience was measured with the Subjective Well-being under Neuroleptic treatment scale (SWN) after a stable dose period of at least 6 weeks of olanzapine, risperidone or haloperidol. To determine the levels of striatal D2 receptor occupancy, [123I]IBZM SPECT imaging was performed. 2. We sought to identify which aspects of subjective wellbeing are most strongly related to dopamine D2 receptor occupancy. Results: 1. Higher striatal D2 receptor occupancy by typical and atypical antipsychotics is related to worse subjective experience, more severe negative symptoms, and depression. Individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergicblocking drugs. There is preliminary evidence that a window of
$491
striatal D2 receptor occupancy between 60% and 70% is optimal for the subjective experience of patients. These occupancies are often reached even with low dosages of antipsychotic drugs. 2. Monitoring feelings of comfort, self-confidence, and safety may guide clinicians and researchers to find the optimal dopamine D2 receptor occupancy. Conclusions: Dopaminergic neurotransmission is relevant for subjective experience. Reaching an optimal dopamine D2 receptor occupancy is clinically relevant, since subjective experience associated with antipsychotic medication is related to medication compliance. Antipsychotic drug dosages often need to be lower than levels in common use.
•
Effect of antipsychotics on low serum brain derived neurotrophic factor levels in schizophrenia
S. Pirildar 1 *, A.S. Gonul 1, F. Taneli 2, F. Akdeniz 1 . ]Ege
University, Psychiatty, Izm#; Turkey; 2Celal Bayar University, Biochemistty, Turkey There is a line of evidence that disruption of neurotrophins could play a role in the etiology of schizophrenia and antipsychotics show their effect by altering levels of neurotrophins. In the present study, we aimed to determine serum BDNF levels between untretaed schizophrenia patients and healthy subjects and the effect of antipsychotics on serum BDNF levels in patients with schizophrenia. Twenty-two schizophrenia patients who didn't take any psychotropic drugs at least for a period of two weeks were enrolled. The mean age of the patients was 27.81±9.54 years (range: 17 47 years). Their mean age at onset of psychosis was 24.36±3.07 years and mean duration of illness was 15.2±13.04 months (range: 6 82 months). The control group consisted of 22 age (7 male, 15 female), and sex-matched physically and mentally healthy subjects who volunteered to participate in the study. Exclusion criteria: having any other physical illness, organic brain disorder, alcohol and/or drug abuse and being pregnant. PANSS scale was used to analyze the positive and negative symptoms and blood samples were collected at baseline and after six weeks of treatment period. Blood samples were collected from the control group, as well. Seventeen patients received risperidone (mean dose 4 m g daily), two received clozapine (mean dose 4 5 0 m g daily) and the remaining three received olanzapine (mean dose 25 mg daily). Wilcoxon signed ranks test was applied for comparisons between baseline and post-treatment serum BDNF levels of patients. Mann Whitney U test was used for comparison serum BDNF levels of patients and control group. Relationship of BDNF levels with PANSS scores were assessed by means of spearman correlations. The baseline serum BDNF levels of patients were lower than controls' (t 4.56; d.f. 21, p<0.001). After 6 weeks of antipsychotic treatment, positive scores (t 7.0; d.f. 21, p < 0.001), negative scores (t 7.4; d.f. 21, p < 0 . 0 0 1 ) and general psychopathology scores (t 20.9; d.f. 27, p <0.001) for PANSS decreased significantly. There was no statistically significance between pre- and post-treatment BDNF levels (p > 0.05). The major finding of this study was that serum BDNF levels of untreated schizophrenia patients were significantly lower than the healthy controls' suggesting that BDNF would be implicated in some neurodevelopmental aspects of schizophrenia. We didn't detect any alteration in serum BDNF levels of the schizophrenia patients after antipsychotic treatment. Shimizu et al (2003) reported that antipsychotic treatment would not change serum BDNF levels in schizophrenia patients.
P3 Psychotic disorders and antipsychotics
$492
References [1] Durany, N., Michel, T., Zochling, R., Boissl, K.W., Cruz-Sanchez, F.F., Riederer, R, Thome, J., 2001. Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses, SchizophL:Res. 52, 79 86. [2] Toyooka, K. Asama, K. Watanabe, Y., Mtu'atake, T., Takahashi, M., Someya, T., Nawa, H., 2002. Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients, Psychiatry Res. 110, 24~257. [3] Shimizu, E., Hashimato, K. Watanabe, H., Komatsu, N., Okamura, N., Koike, K., Shinado, N., Nakazato, M., Kumakiri, N., Okada, S.O., Iyo, M., 2003. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia are indistinguishable from controls, Neurosci. Letters 351, 1114.
•
Serum brain derived neurotrophic factor levels in schizophrenic patients treated with olanzapine and clozapine
our results support the hypothesis of our study BDNF remains as an interesting molecule for further detailed research to evaluate the effect of BDNF in the pathogenesis of schizophrenia.
References [1] Durany, N., Michel, T., Zochling, R., Boissl, K.W., Cruz-Sanchez, F.F., Riederer, R, Thome, J., 2001. Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses, Schizophr. Res. 52, 79 86. [2] Fourney, J.C., Ashe, P., Nylen, K., Juorio, A.V., Li, X.M., 2002. Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration, Brain Res. 954, 11 20. [3] Pirildar, S., G6nfil, A.S., Taneli, E, Akdeniz, E, 2004. Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment. Prog Neuropsychopharmacol Biol Psychiatry. Jul; 28(4): 709 13.
•
Comparison between responders and nonresponders in first-episode schizophrenia
S. Pirildar 1 *, F. Taneli 2, L. Mete 3, A.S. Gonul 1, O. Kucuk 1, N. Zorlu 1 . ]Ege University, Psychiatty, Izmir, Turkey; 2Celal
E. Ceskova*, R.R Prikryl, T.K. Kasparek, H.K. Kucerova.
Bayar University, Biochemistty, Turkey; 3Ataturk Education and Training Hospital, Psychiatty, Turkey
Masmyk University, Department of Psychiatty, Brno, Czech Republic
Several studies indicate that neurotropins have a role in the etiology and treatment of schizophrenia. It is suggested that antipsychotics improve the symptoms of schizophrenia ~except altering neurotransmitters- via regulation of genes involving remodeling and survival of adult neurons and neurotrophins. The aim of the study is to investigate the effect of clozapine and olanzapine on serum BDNF levels in patinets with schizophrenia. Fifty-five patients with schizophrenia using olanzapine or clozapine at least for 6 months were enrolled into the study. The control group was consisted of schizophrenia patients who didn't use any psychotropic drugs at least for 2 weeks. Their mean age was for olanzapine group (34.50±10.04); clozapine group (29.15±6.89); control group (27.79±8.99) years. The duration of their illness was for olanzapine group (73.50±80.32); clozapine group (74.25±36.55) control group (25.83±30.36) month. In our analyzes we used the PANNS scale to evaluate the positive and negative symptoms. Blood samples were collected for each patient at the index admission to evaluate serum BDNF levels. The exclusion criteria: using any other psychotropics, having organic brain disorder, alcohol or drug abuse, pregnancy, or any physical illness. Results: PANSS scores were (general. positive, negative) 27.65±14.20; 14.85±10.39; 17.75±7.97 in clozapine group; 21.25±5.59; 10.25±2.49; 13.33±5.21 in olanzapine group and 57.70±10.66; 32.58±0.05; 30.04±7.03 in drug-free patients. Serum BDNF level of clozapine group was 16.27±2.45; of olanzapine group 21.91±6.07 and of drug-free patients 14.19±8.12 Using ANOVA we detected higher serum BDNF levels of patients treated with clozapine and olanzapine than drug-free patients (df 2; f 4.920; p 0.01). There was a positive correlation between positive PANSS scores and BDNF levels (p 0.027; t 0.263) using pearson correlation test. In this study we detect high serum BDNF levels after treatment with clozapine and olanzapine than the drug-free schizophrenic patients. In our previous study we did not found any alteration in serum BDNF levels after six weeks of antipsychotic treatment. In that study 15 of 22 received risperidone for a period of six weeks. It is reported that antipsychotics with powerful D2 receptor antagonism properties like haloperidol significantly decreased hippocampal BDNF mRNA in the CA1. BDNF is upregulated by antipsychotic treatments with 5HT2A receptor blockade properties. Although
Purposes of the study: 1) to assess in details the psychopathology before and after the acute antipsychotic treatment, 2) to compare responders and nonresponders. Methods used: Male patients consecutively (November 1997 to March 2004) hospitalised with first-episode schizophrenia (according to ICD 10) were included. Clinical assessment was performed using the Positive and Negative Syndrome Scale (PANSS) after admission (before treatment) and at discharge. The response rate (defined as minimally 30% reduction from baseline in the PANSS total score) was evaluated at discharge. After a baseline assessment all patients were treated openly by monotherapy with an antipsychotic, the doses were inidividualised. The statistical analysis was made by means of the t-test (the Wilcoxon matched-pairs test and testing for differences between means). Results: The study included 104 inpatients. Their average age was 23.3 (SD 5.7) years, the mean duration of the hospitalisation 44.5 (15.3) days and the mean length of illness, determined from the time the patients first exhibited illness-related behavioural symptoms 0.77 (1.0) years. 28 patients were treated with classical antipsychotics, 64 patients with risperidone, 12 patients with others 2nd generation antipsychotics. Scores for all symptoms decreased significantly before discharge, in average 44 days after admission. The negative symptoms improved less, compared to the positive ones. On admission in the total sample the most frequently observed symptoms were lack of judgement and insight (in 87.6% of patients), suspiciousness/feelings of persecution (82%), delusions (77%). Individual negative symptoms were present in about one half of the patients. At discharge the most frequent symptoms were again lack of judgement and insight (55.7%) and blunted affect (22%). We identified 76 responders (73%). On admission, responders compared with nonresponders had significantly higher scores on the total and all the subscales of PANSS and significantly higher scores of 21 individual items out of 30 items. On the contrary, at discharge the responders compared with nonresponders had significantly lower scores on the total and all subscales of PANSS and significantly lower psychopathology in 25 out of 30 items of individual symptoms. In nonresponders no decrease of the negative subscale of PANSS was found during the treatment. The means score of some negative symptoms mildly increased (blunted affect, lack of spontaneity). The most striking difference between responders and noresponders