The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Sunao Kaneko - One of the best experts on this subject based on the ideXlab platform.
-
single oral dose kinetics of Zotepine and its relationship to prolactin response and side effects
Therapeutic Drug Monitoring, 1998Co-Authors: O Tanaka, Tsuyoshi Kondo, Noboru Tokinaga, Koichi Otani, Norio Yasui, Sunao KanekoAbstract:Summary:The authors investigated the single oral dose kinetics of Zotepine and its relationship with prolactin response and side effects in 14 healthy male volunteers. Each subject took a single oral 25-mg dose of Zotepine, and plasma concentrations of Zotepine, prolactin, and their side effects wer
-
possible inhibitory effect of diazepam on the metabolism of Zotepine an antipsychotic drug
Psychopharmacology, 1996Co-Authors: Tsuyoshi Kondo, O Tanaka, K Otani, Kazuo Mihara, Noboru Tokinaga, Sunao Kaneko, Kan Chiba, Takashi IshizakiAbstract:Effects of smoking and cytochrome P450 2C19 (CYP2C19) status on the single dose kinetics of Zotepine and pharmacokinetic interaction between Zotepine and diazepam were investigated. In 14 healthy volunteers, the pharmacokinetics of Zotepine after a single oral 25 mg dose were compared between eight smokers and six non-smokers, or between seven extensive metabolizers (EMs) and seven poor metabolizers (PMs) of S-mephenytoin. There was no significant difference in any pharmacokinetic parameters between smokers and non-smokers, or between the EM and PM groups. In 17 patients treated with Zotepine 80–340 mg/day, intra-individual changes in plasma concentrations of Zotepine caused by coadministration of diazepam 10 mg/day for 2 weeks were examined. Plasma concentrations of Zotepine were significantly increased after coadministration of diazepam (P < 0.05). Consequently, it is suggested that neither smoking nor CYP2C19 status affects the metabolism of Zotepine. The elevation in plasma concentrations of Zotepine after coadministration of diazepam may be a result of competitive inhibition of Zotepine metabolism by diazepam via other isoenzyme than CYP2C19, e.g., CYP3A4.
-
adverse effects of Zotepine and their relationship to serum concentrations of the drug and prolactin
Therapeutic Drug Monitoring, 1994Co-Authors: Tsuyoshi Kondo, O Tanaka, Sunao Kaneko, Koichi Otani, Masayuki Ishida, Yutaka FukushimaAbstract:: Adverse effects of Zotepine, an antipsychotic drug, and their relationship to serum concentrations of the drug and prolactin were investigated in 28 schizophrenic in-patients. The daily dose was 100 mg during the first week and 200 mg during the next 3 weeks. Adverse effects were evaluated by the UKU Side Effect Rating Scale (21 items). The mean (+/- SD) total UKU score at the end of the study was 3.1 +/- 2.5, indicating mild adverse effects. The scores of psychic adverse effects at 2 weeks and total adverse effects at 3 and 4 weeks were significantly higher in nonresponders than in responders (p < 0.05). Furthermore, there was a significant inverse correlation between percent improvement in total Brief Psychiatric Rating Scale (BPRS) scores and total UKU scores at 4 weeks (p < 0.05). These results suggest a relationship between poor clinical response and increased adverse effects during Zotepine treatment. Only the scores of akathisia at 2 weeks showed a significantly positive correlation with serum Zotepine concentrations (p < 0.05). No correlation was found between prolactin response and neurological adverse effects.
-
correlation between prolactin response and therapeutic effects of Zotepine in schizophrenic patients
International Clinical Psychopharmacology, 1994Co-Authors: K Otani, Tsuyoshi Kondo, Sunao Kaneko, Masayuki Ishida, Y FukushimaAbstract:: The correlation between prolactin response and therapeutic effects of Zotepine, as assessed by the Brief Psychiatric Rating Scale, was studied in 24 schizophrenic patients (12 males, 12 females), after 4 weeks of treatment. The daily dose was 100 mg in the first week, and 200 mg for the next 3 weeks. There were significant (p < 0.05) positive correlations between changes in serum prolactin concentration and amelioration scores of positive or total symptoms in males only. Thus, prolactin response may reflect therapeutic effects of Zotepine, at least in males.
-
a study of the therapeutic spectrum of a fixed dose of Zotepine and its relationship with serum concentrations of the drug
Human Psychopharmacology-clinical and Experimental, 1993Co-Authors: Tsuyoshi Kondo, O Tanaka, K Otani, Kazuo Mihara, Sunao Kaneko, Masayuki Ishida, Yutaka FukushimaAbstract:The therapeutic spectrum of Zotepine, an antipsychotic drug, and its relationship with serum concentrations of the drug were investigated by a fixed-dose study (100 mg/day in the first week, and 200 mg/day for the next 3 weeks) in 20 schizophrenic in-patients. The mean percentages of symptom reduction in total Brief Psychiatric Rating Scale (BPRS) and three subgroups were 63.4 per cent for total, 64.4 per cent for positive symptoms, 41.8 per cent for negative symptoms and 74.2 per cent for anxiety-depression respectively. Total, positive and negative symptoms were significantly reduced after 2 weeks (p < 0.01), while a significant reduction in anxiety-depression symptoms was already found after 1 week (p < 0.01). There were significant differences in the values of percentage improvement in total and positive symptoms after 2 weeks (p < 0.05) and negative symptoms after 1 week (p < 0.05) between responders (more than 50 per cent reduction in total BPRS scores at the end of the study) and nonresponders. In 18 patients (90 per cent), the clinical response at 2 weeks corresponded well to the final outcome. No definite relationship was found between serum Zotepine concentrations and the clinical efficacy.
Yutaka Fukushima - One of the best experts on this subject based on the ideXlab platform.
-
adverse effects of Zotepine and their relationship to serum concentrations of the drug and prolactin
Therapeutic Drug Monitoring, 1994Co-Authors: Tsuyoshi Kondo, O Tanaka, Sunao Kaneko, Koichi Otani, Masayuki Ishida, Yutaka FukushimaAbstract:: Adverse effects of Zotepine, an antipsychotic drug, and their relationship to serum concentrations of the drug and prolactin were investigated in 28 schizophrenic in-patients. The daily dose was 100 mg during the first week and 200 mg during the next 3 weeks. Adverse effects were evaluated by the UKU Side Effect Rating Scale (21 items). The mean (+/- SD) total UKU score at the end of the study was 3.1 +/- 2.5, indicating mild adverse effects. The scores of psychic adverse effects at 2 weeks and total adverse effects at 3 and 4 weeks were significantly higher in nonresponders than in responders (p < 0.05). Furthermore, there was a significant inverse correlation between percent improvement in total Brief Psychiatric Rating Scale (BPRS) scores and total UKU scores at 4 weeks (p < 0.05). These results suggest a relationship between poor clinical response and increased adverse effects during Zotepine treatment. Only the scores of akathisia at 2 weeks showed a significantly positive correlation with serum Zotepine concentrations (p < 0.05). No correlation was found between prolactin response and neurological adverse effects.
-
a study of the therapeutic spectrum of a fixed dose of Zotepine and its relationship with serum concentrations of the drug
Human Psychopharmacology-clinical and Experimental, 1993Co-Authors: Tsuyoshi Kondo, O Tanaka, K Otani, Kazuo Mihara, Sunao Kaneko, Masayuki Ishida, Yutaka FukushimaAbstract:The therapeutic spectrum of Zotepine, an antipsychotic drug, and its relationship with serum concentrations of the drug were investigated by a fixed-dose study (100 mg/day in the first week, and 200 mg/day for the next 3 weeks) in 20 schizophrenic in-patients. The mean percentages of symptom reduction in total Brief Psychiatric Rating Scale (BPRS) and three subgroups were 63.4 per cent for total, 64.4 per cent for positive symptoms, 41.8 per cent for negative symptoms and 74.2 per cent for anxiety-depression respectively. Total, positive and negative symptoms were significantly reduced after 2 weeks (p < 0.01), while a significant reduction in anxiety-depression symptoms was already found after 1 week (p < 0.01). There were significant differences in the values of percentage improvement in total and positive symptoms after 2 weeks (p < 0.05) and negative symptoms after 1 week (p < 0.05) between responders (more than 50 per cent reduction in total BPRS scores at the end of the study) and nonresponders. In 18 patients (90 per cent), the clinical response at 2 weeks corresponded well to the final outcome. No definite relationship was found between serum Zotepine concentrations and the clinical efficacy.
-
A study of the therapeutic spectrum of a fixed‐dose of Zotepine and its relationship with serum concentrations of the drug
Human Psychopharmacology-clinical and Experimental, 1993Co-Authors: Tsuyoshi Kondo, O Tanaka, Kazuo Mihara, Sunao Kaneko, Koichi Otani, Masayuki Ishida, Yutaka FukushimaAbstract:The therapeutic spectrum of Zotepine, an antipsychotic drug, and its relationship with serum concentrations of the drug were investigated by a fixed-dose study (100 mg/day in the first week, and 200 mg/day for the next 3 weeks) in 20 schizophrenic in-patients. The mean percentages of symptom reduction in total Brief Psychiatric Rating Scale (BPRS) and three subgroups were 63.4 per cent for total, 64.4 per cent for positive symptoms, 41.8 per cent for negative symptoms and 74.2 per cent for anxiety-depression respectively. Total, positive and negative symptoms were significantly reduced after 2 weeks (p < 0.01), while a significant reduction in anxiety-depression symptoms was already found after 1 week (p < 0.01). There were significant differences in the values of percentage improvement in total and positive symptoms after 2 weeks (p < 0.05) and negative symptoms after 1 week (p < 0.05) between responders (more than 50 per cent reduction in total BPRS scores at the end of the study) and nonresponders. In 18 patients (90 per cent), the clinical response at 2 weeks corresponded well to the final outcome. No definite relationship was found between serum Zotepine concentrations and the clinical efficacy.
-
prolactin response to Zotepine in schizophrenic patients
Human Psychopharmacology-clinical and Experimental, 1993Co-Authors: K Otani, Tsuyoshi Kondo, Sunao Kaneko, Masayuki Ishida, Hiroshi Sasa, Hisashi Higuchi, Yutaka FukushimaAbstract:The prolactin response to an antipsychotic drug Zotepine, which has both antidopaminergic and antiserotonergic effects, was studied in 24 inpatients suffering from schizophrenia. The daily dose was 100 mg in the first week, and 200 mg for the next three weeks. The mean serum concentrations of prolactin at the daily dose of 200 mg, but not 100 mg, were significantly higher than that before treatment. The δ prolactin (the change from the pretreatment concentration) was significantly correlated with Zotepine concentrations at each week. At low Zotepine concentrations, patients with high pre-treatment prolactin concentrations showed negative δ prolactin. The present study thus suggests that at high concentrations Zotepine shows predominantly antidopaminergic effects, while at low concentrations its antiserotonergic effects are predominant and/or it acts as a dopamine agonist.
-
steady state serum kinetics of Zotepine
Human Psychopharmacology-clinical and Experimental, 1992Co-Authors: K Otani, Kazuo Mihara, Sunao Kaneko, Takayuki Hirano, T Kondo, Yutaka FukushimaAbstract:The steady-state serum kinetics of Zotepine, an antipsychotic drug, were studied in 59 psychiatric in-patients receiving 50–500 mg/day (mean 215 mg/day) of the drug. There was a 26-fold inter-individual variation in the concentration/dose ratios (C/D ratios: ng/ml/mg/kg), which ranged from 2.4 to 62.2 (mean 13.2). The smokers (n = 37) had significantly lower C/D ratios (mean ±SD: 9.7 ± 7.0 vs 19.0 ± 15.5, p < 0.01), while the patients co-administered benzodiazepines (n = 14) had significantly higher C/D ratios (19.06 ± 12.5 vs 11.2 ± 10.9, p < 0.01) than the others. There was no significant relationship between the C/D ratios and age or gender. In the 24 cases where the dose was fixed at 100 mg/day in the first week and at 200 mg/day for the next 3 weeks, no significant difference was found in the mean C/D ratios during the 4 weeks. The present study thus suggests a large inter-individual variation in the metabolism of Zotepine, and that smoking enhances, and co-administration of benzodiazepines inhibits, the metabolism. Age and gender do not affect the kinetics of the drug. The results also suggest no dose-dependent kinetics and no enzyme-inducing effect of the drug.
Tsuyoshi Kondo - One of the best experts on this subject based on the ideXlab platform.
-
single oral dose kinetics of Zotepine and its relationship to prolactin response and side effects
Therapeutic Drug Monitoring, 1998Co-Authors: O Tanaka, Tsuyoshi Kondo, Noboru Tokinaga, Koichi Otani, Norio Yasui, Sunao KanekoAbstract:Summary:The authors investigated the single oral dose kinetics of Zotepine and its relationship with prolactin response and side effects in 14 healthy male volunteers. Each subject took a single oral 25-mg dose of Zotepine, and plasma concentrations of Zotepine, prolactin, and their side effects wer
-
possible inhibitory effect of diazepam on the metabolism of Zotepine an antipsychotic drug
Psychopharmacology, 1996Co-Authors: Tsuyoshi Kondo, O Tanaka, K Otani, Kazuo Mihara, Noboru Tokinaga, Sunao Kaneko, Kan Chiba, Takashi IshizakiAbstract:Effects of smoking and cytochrome P450 2C19 (CYP2C19) status on the single dose kinetics of Zotepine and pharmacokinetic interaction between Zotepine and diazepam were investigated. In 14 healthy volunteers, the pharmacokinetics of Zotepine after a single oral 25 mg dose were compared between eight smokers and six non-smokers, or between seven extensive metabolizers (EMs) and seven poor metabolizers (PMs) of S-mephenytoin. There was no significant difference in any pharmacokinetic parameters between smokers and non-smokers, or between the EM and PM groups. In 17 patients treated with Zotepine 80–340 mg/day, intra-individual changes in plasma concentrations of Zotepine caused by coadministration of diazepam 10 mg/day for 2 weeks were examined. Plasma concentrations of Zotepine were significantly increased after coadministration of diazepam (P < 0.05). Consequently, it is suggested that neither smoking nor CYP2C19 status affects the metabolism of Zotepine. The elevation in plasma concentrations of Zotepine after coadministration of diazepam may be a result of competitive inhibition of Zotepine metabolism by diazepam via other isoenzyme than CYP2C19, e.g., CYP3A4.
-
adverse effects of Zotepine and their relationship to serum concentrations of the drug and prolactin
Therapeutic Drug Monitoring, 1994Co-Authors: Tsuyoshi Kondo, O Tanaka, Sunao Kaneko, Koichi Otani, Masayuki Ishida, Yutaka FukushimaAbstract:: Adverse effects of Zotepine, an antipsychotic drug, and their relationship to serum concentrations of the drug and prolactin were investigated in 28 schizophrenic in-patients. The daily dose was 100 mg during the first week and 200 mg during the next 3 weeks. Adverse effects were evaluated by the UKU Side Effect Rating Scale (21 items). The mean (+/- SD) total UKU score at the end of the study was 3.1 +/- 2.5, indicating mild adverse effects. The scores of psychic adverse effects at 2 weeks and total adverse effects at 3 and 4 weeks were significantly higher in nonresponders than in responders (p < 0.05). Furthermore, there was a significant inverse correlation between percent improvement in total Brief Psychiatric Rating Scale (BPRS) scores and total UKU scores at 4 weeks (p < 0.05). These results suggest a relationship between poor clinical response and increased adverse effects during Zotepine treatment. Only the scores of akathisia at 2 weeks showed a significantly positive correlation with serum Zotepine concentrations (p < 0.05). No correlation was found between prolactin response and neurological adverse effects.
-
correlation between prolactin response and therapeutic effects of Zotepine in schizophrenic patients
International Clinical Psychopharmacology, 1994Co-Authors: K Otani, Tsuyoshi Kondo, Sunao Kaneko, Masayuki Ishida, Y FukushimaAbstract:: The correlation between prolactin response and therapeutic effects of Zotepine, as assessed by the Brief Psychiatric Rating Scale, was studied in 24 schizophrenic patients (12 males, 12 females), after 4 weeks of treatment. The daily dose was 100 mg in the first week, and 200 mg for the next 3 weeks. There were significant (p < 0.05) positive correlations between changes in serum prolactin concentration and amelioration scores of positive or total symptoms in males only. Thus, prolactin response may reflect therapeutic effects of Zotepine, at least in males.
-
a study of the therapeutic spectrum of a fixed dose of Zotepine and its relationship with serum concentrations of the drug
Human Psychopharmacology-clinical and Experimental, 1993Co-Authors: Tsuyoshi Kondo, O Tanaka, K Otani, Kazuo Mihara, Sunao Kaneko, Masayuki Ishida, Yutaka FukushimaAbstract:The therapeutic spectrum of Zotepine, an antipsychotic drug, and its relationship with serum concentrations of the drug were investigated by a fixed-dose study (100 mg/day in the first week, and 200 mg/day for the next 3 weeks) in 20 schizophrenic in-patients. The mean percentages of symptom reduction in total Brief Psychiatric Rating Scale (BPRS) and three subgroups were 63.4 per cent for total, 64.4 per cent for positive symptoms, 41.8 per cent for negative symptoms and 74.2 per cent for anxiety-depression respectively. Total, positive and negative symptoms were significantly reduced after 2 weeks (p < 0.01), while a significant reduction in anxiety-depression symptoms was already found after 1 week (p < 0.01). There were significant differences in the values of percentage improvement in total and positive symptoms after 2 weeks (p < 0.05) and negative symptoms after 1 week (p < 0.05) between responders (more than 50 per cent reduction in total BPRS scores at the end of the study) and nonresponders. In 18 patients (90 per cent), the clinical response at 2 weeks corresponded well to the final outcome. No definite relationship was found between serum Zotepine concentrations and the clinical efficacy.
K Otani - One of the best experts on this subject based on the ideXlab platform.
-
possible inhibitory effect of diazepam on the metabolism of Zotepine an antipsychotic drug
Psychopharmacology, 1996Co-Authors: Tsuyoshi Kondo, O Tanaka, K Otani, Kazuo Mihara, Noboru Tokinaga, Sunao Kaneko, Kan Chiba, Takashi IshizakiAbstract:Effects of smoking and cytochrome P450 2C19 (CYP2C19) status on the single dose kinetics of Zotepine and pharmacokinetic interaction between Zotepine and diazepam were investigated. In 14 healthy volunteers, the pharmacokinetics of Zotepine after a single oral 25 mg dose were compared between eight smokers and six non-smokers, or between seven extensive metabolizers (EMs) and seven poor metabolizers (PMs) of S-mephenytoin. There was no significant difference in any pharmacokinetic parameters between smokers and non-smokers, or between the EM and PM groups. In 17 patients treated with Zotepine 80–340 mg/day, intra-individual changes in plasma concentrations of Zotepine caused by coadministration of diazepam 10 mg/day for 2 weeks were examined. Plasma concentrations of Zotepine were significantly increased after coadministration of diazepam (P < 0.05). Consequently, it is suggested that neither smoking nor CYP2C19 status affects the metabolism of Zotepine. The elevation in plasma concentrations of Zotepine after coadministration of diazepam may be a result of competitive inhibition of Zotepine metabolism by diazepam via other isoenzyme than CYP2C19, e.g., CYP3A4.
-
correlation between prolactin response and therapeutic effects of Zotepine in schizophrenic patients
International Clinical Psychopharmacology, 1994Co-Authors: K Otani, Tsuyoshi Kondo, Sunao Kaneko, Masayuki Ishida, Y FukushimaAbstract:: The correlation between prolactin response and therapeutic effects of Zotepine, as assessed by the Brief Psychiatric Rating Scale, was studied in 24 schizophrenic patients (12 males, 12 females), after 4 weeks of treatment. The daily dose was 100 mg in the first week, and 200 mg for the next 3 weeks. There were significant (p < 0.05) positive correlations between changes in serum prolactin concentration and amelioration scores of positive or total symptoms in males only. Thus, prolactin response may reflect therapeutic effects of Zotepine, at least in males.
-
a study of the therapeutic spectrum of a fixed dose of Zotepine and its relationship with serum concentrations of the drug
Human Psychopharmacology-clinical and Experimental, 1993Co-Authors: Tsuyoshi Kondo, O Tanaka, K Otani, Kazuo Mihara, Sunao Kaneko, Masayuki Ishida, Yutaka FukushimaAbstract:The therapeutic spectrum of Zotepine, an antipsychotic drug, and its relationship with serum concentrations of the drug were investigated by a fixed-dose study (100 mg/day in the first week, and 200 mg/day for the next 3 weeks) in 20 schizophrenic in-patients. The mean percentages of symptom reduction in total Brief Psychiatric Rating Scale (BPRS) and three subgroups were 63.4 per cent for total, 64.4 per cent for positive symptoms, 41.8 per cent for negative symptoms and 74.2 per cent for anxiety-depression respectively. Total, positive and negative symptoms were significantly reduced after 2 weeks (p < 0.01), while a significant reduction in anxiety-depression symptoms was already found after 1 week (p < 0.01). There were significant differences in the values of percentage improvement in total and positive symptoms after 2 weeks (p < 0.05) and negative symptoms after 1 week (p < 0.05) between responders (more than 50 per cent reduction in total BPRS scores at the end of the study) and nonresponders. In 18 patients (90 per cent), the clinical response at 2 weeks corresponded well to the final outcome. No definite relationship was found between serum Zotepine concentrations and the clinical efficacy.
-
prolactin response to Zotepine in schizophrenic patients
Human Psychopharmacology-clinical and Experimental, 1993Co-Authors: K Otani, Tsuyoshi Kondo, Sunao Kaneko, Masayuki Ishida, Hiroshi Sasa, Hisashi Higuchi, Yutaka FukushimaAbstract:The prolactin response to an antipsychotic drug Zotepine, which has both antidopaminergic and antiserotonergic effects, was studied in 24 inpatients suffering from schizophrenia. The daily dose was 100 mg in the first week, and 200 mg for the next three weeks. The mean serum concentrations of prolactin at the daily dose of 200 mg, but not 100 mg, were significantly higher than that before treatment. The δ prolactin (the change from the pretreatment concentration) was significantly correlated with Zotepine concentrations at each week. At low Zotepine concentrations, patients with high pre-treatment prolactin concentrations showed negative δ prolactin. The present study thus suggests that at high concentrations Zotepine shows predominantly antidopaminergic effects, while at low concentrations its antiserotonergic effects are predominant and/or it acts as a dopamine agonist.
-
steady state serum kinetics of Zotepine
Human Psychopharmacology-clinical and Experimental, 1992Co-Authors: K Otani, Kazuo Mihara, Sunao Kaneko, Takayuki Hirano, T Kondo, Yutaka FukushimaAbstract:The steady-state serum kinetics of Zotepine, an antipsychotic drug, were studied in 59 psychiatric in-patients receiving 50–500 mg/day (mean 215 mg/day) of the drug. There was a 26-fold inter-individual variation in the concentration/dose ratios (C/D ratios: ng/ml/mg/kg), which ranged from 2.4 to 62.2 (mean 13.2). The smokers (n = 37) had significantly lower C/D ratios (mean ±SD: 9.7 ± 7.0 vs 19.0 ± 15.5, p < 0.01), while the patients co-administered benzodiazepines (n = 14) had significantly higher C/D ratios (19.06 ± 12.5 vs 11.2 ± 10.9, p < 0.01) than the others. There was no significant relationship between the C/D ratios and age or gender. In the 24 cases where the dose was fixed at 100 mg/day in the first week and at 200 mg/day for the next 3 weeks, no significant difference was found in the mean C/D ratios during the 4 weeks. The present study thus suggests a large inter-individual variation in the metabolism of Zotepine, and that smoking enhances, and co-administration of benzodiazepines inhibits, the metabolism. Age and gender do not affect the kinetics of the drug. The results also suggest no dose-dependent kinetics and no enzyme-inducing effect of the drug.
Stefan Leucht - One of the best experts on this subject based on the ideXlab platform.
-
quetiapine versus other atypical antipsychotics for schizophrenia
Cochrane Database of Systematic Reviews, 2010Co-Authors: Laila Asmal, Christine Rummelkluge, Katja Komossa, Srnka J Flegar, Jikun Wang, Stefan LeuchtAbstract:Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness.To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and Zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses.We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies.All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders.We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model.The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with Zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than olanzapine (9 RCTs, n=1674, RR 1.60 CI 1.07 to 2.40, NNT 25 CI 15 to 73) and risperidone (6 RCTs, n=627, RR 1.88 CI 1.11 to 3.21, NNT 16 CI 9 to 59). Fewer participants in the clozapine groups left the trials early due to inefficacy than risperidone (6 RCTs, n=627, RR 0.40 CI 0.23 to 0.70, NNT 11 CI 7 to 21), suggesting a certain higher efficacy of clozapine.Clozapine was more efficacious than Zotepine in improving the participants general mental state (BPRS total score: 1 RCT, n=59, MD -6.00 CI -9.83 to -2.17), but not consistently more than olanzapine, quetiapine, risperidone and ziprasidone. There was no significant difference between clozapine and olanzapine or risperidone in terms of positive or negative symptoms of schizophrenia. According to two studies from China quetiapine was more efficacious for negative symptoms than clozapine (2 RCTs, n=142, MD 2.23 CI 0.99 to 3.48).Clozapine produced somewhat fewer extrapyramidal side-effects than risperidone (use of antiparkinson medication: 6 RCTs, n=304, RR 0.39 CI 0.22 to 0.68, NNT 7 CI 5 to 18) and Zotepine (n=59, RR0.05 CI 0.00 to 0.86, NNT 3 CI 2 to 5). More participants in the clozapine group showed decreased white blood cells than those taking olanzapine, more hypersalivation and sedation than those on olanzapine, risperidone and quetiapine and more seizures than people on olanzapine and risperidone. Also clozapine produced an important weight gain not seen with risperidone.Other differences in adverse effects were less documented and should be replicated, for example, clozapine did not alter prolactin levels whereas olanzapine, risperidone and Zotepine did; compared with quetiapine, clozapine produced a higher incidence of electrocardiogram (ECG) alterations; and compared with quetiapine and risperidone clozapine produced a higher increase of triglyceride levels. Other findings that should be replicated were: clozapine improved social functioning less than risperidone and fewer participants in the clozapine group had to be hospitalised to avoid suicide attempts compared to olanzapine.Other important outcomes such as service use, cognitive functioning, satisfaction with care or quality of life were rarely reported.Clozapine may be a little more efficacious than Zotepine and risperidone but further trials are required to confirm this finding. Clozapine differs more clearly in adverse effects from other second generation antipsychotics and the side-effect profile could be key in the selection of treatment depending on the clinical situation and a patient's preferences. Data on other important outcomes such as cognitive functioning, quality of life, death or service use are currently largely missing, making further large and well-designed trials necessary. It is also important to take into account that the large number of people leaving the studies early limits the validity and interpretation of our findings.
-
head to head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia a systematic review and meta analysis
Schizophrenia Research, 2010Co-Authors: Christine Rummelkluge, Heike Hunger, Franziska Schmid, Sandra Schwarz, Werner Kissling, Katja Komossa, Claudia Asenjo Lobos, John M Davis, Stefan LeuchtAbstract:Objective The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, Zotepine.
-
Zotepine versus other atypical antipsychotics for schizophrenia
Cochrane Database of Systematic Reviews, 2010Co-Authors: Selvizhi Subramanian, Christine Rummelkluge, Heike Hunger, Franziska Schmid, Sandra Schwarz, Werner Kissling, Stefan Leucht, Katja KomossaAbstract:In many countries of the industrialised world, second generation (atypical) antipsychotic drugs have become first line treatment for people with schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. In this review we examined how the efficacy and tolerability of Zotepine differs from that of other second generation antipsychotic drugs.To evaluate the effects of Zotepine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychoses.We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL CINAHL, EMBASE, MEDLINE and PsycINFO.We included all randomised trials comparing oral Zotepine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people with schizophrenia or schizophrenia-like psychoses.We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random effects model.The review currently includes data from two short term, ill reported trials (total n=109). Both studies compared Zotepine with clozapine. 34% of people left early but there was no significant difference between groups. Zotepine was less effective than clozapine (no clinically significant response: n=59, 1 RCT, RR 8.23 CI 1.14 to 59.17, NNH 3 CI 2 to 8; average score (BPRS total) at endpoint (n=59, 1 RCT, MD 6.00 CI 2.17 to 9.83). Zotepine induced more movement disorders than clozapine (use of antiparkinson medication: n=59, 1 RCT, RR 18.75 CI 1.17 to 301.08, NNH 3 CI 2 to 5) and higher prolactin levels (n=59, 1 RCT, MD 33.40 CI 14.87 to 51.93). Data on important other outcomes such as other adverse events, service use or satisfaction with care were not available.Zotepine may be less effective than clozapine and associated with more movement disorders and higher prolactin levels, but the evidence base is too small and prone to bias, making any practical recommendations impossible. There is no randomised evidence on the effects of Zotepine compared to second generation antipsychotic drugs other than clozapine. More studies are possible to justify.
-
The Cochrane Library - Zotepine versus other atypical antipsychotics for schizophrenia.
Cochrane Database of Systematic Reviews, 2010Co-Authors: Selvizhi Subramanian, Heike Hunger, Franziska Schmid, Sandra Schwarz, Werner Kissling, Stefan Leucht, Christine Rummel-kluge, Katja KomossaAbstract:In many countries of the industrialised world, second generation (atypical) antipsychotic drugs have become first line treatment for people with schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. In this review we examined how the efficacy and tolerability of Zotepine differs from that of other second generation antipsychotic drugs.To evaluate the effects of Zotepine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychoses.We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL CINAHL, EMBASE, MEDLINE and PsycINFO.We included all randomised trials comparing oral Zotepine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people with schizophrenia or schizophrenia-like psychoses.We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random effects model.The review currently includes data from two short term, ill reported trials (total n=109). Both studies compared Zotepine with clozapine. 34% of people left early but there was no significant difference between groups. Zotepine was less effective than clozapine (no clinically significant response: n=59, 1 RCT, RR 8.23 CI 1.14 to 59.17, NNH 3 CI 2 to 8; average score (BPRS total) at endpoint (n=59, 1 RCT, MD 6.00 CI 2.17 to 9.83). Zotepine induced more movement disorders than clozapine (use of antiparkinson medication: n=59, 1 RCT, RR 18.75 CI 1.17 to 301.08, NNH 3 CI 2 to 5) and higher prolactin levels (n=59, 1 RCT, MD 33.40 CI 14.87 to 51.93). Data on important other outcomes such as other adverse events, service use or satisfaction with care were not available.Zotepine may be less effective than clozapine and associated with more movement disorders and higher prolactin levels, but the evidence base is too small and prone to bias, making any practical recommendations impossible. There is no randomised evidence on the effects of Zotepine compared to second generation antipsychotic drugs other than clozapine. More studies are possible to justify.
-
Zotepine versus other atypical antipsychotics for schizophrenia.
The Cochrane database of systematic reviews, 2010Co-Authors: Selvizhi Subramanian, Heike Hunger, Franziska Schmid, Sandra Schwarz, Werner Kissling, Stefan Leucht, Christine Rummel-kluge, Katja KomossaAbstract:In many parts of the world, particularly in industrialised countries, second generation (atypical) antipsychotic drugs have become first line treatment for people suffering from schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. To evaluate the effects of Zotepine compared with other second generation antipsychotic drugs for people suffering from schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Group Trials Register (November 2009), inspected references of all identified studies for further trials and contacted authors of trials for additional information. We included only randomised clinical controlled trials that compared Zotepine with any forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people suffering from only schizophrenia or schizophrenia-like psychoses. SS and KK extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. We included three studies (total n=289; 2 RCTs Zotepine vs clozapine; 1 RCT Zotepine vs clozapine vs risperidone (at 4 mg, 8 mg doses) vs remoxipride. All studies were of limited methodological quality. When Zotepine was compared with clozapine, it was clozapine that was found to be more effective in terms of global state (n=59, 1 RCT, RR No clinically significant response 8.23 CI 1.14 to 59.17). Mental state scores also favoured clozapine (n=59, 1 RCT, MD average score (BPRS total, high = poor) 6.00 CI 2.17 to 9.83) and there was less use of antiparkinson medication in the clozapine group (n=116, 2 RCTs, RR 20.96 CI 2.89 to 151.90). In the comparison of Zotepine and risperidone, mental state scoring found no significant difference between the groups (vs 4 mg: n=40, 1 RCT, MD average endpoint score (BPRS total, high=poor) 1.40 CI -9.82 to 12.62; vs 8 mg: n=40, 1 RCT, MD -1.30 CI -12.95 to 10.35) and use of antiparkinson medication was equivocal (vs 4 mg: n=40, 1 RCT, MD 1.80 CI -0.64 to 4.24; vs 8 mg: n=40, 1 RCT, MD 2.50 CI -0.05 to 5.05). Finally, when Zotepine was compared with remoxipride, again no effect was found for mental state (n=58, 1 RCT, MD average endpoint score (BPRS total, high=poor) 5.70 CI -4.13 to 15.53) and there was no significant difference between the two groups in terms of use of antiparkinson medication (n=49, 1 RCT, RR 0.97 CI 0.41 to 2.29).Data on important other outcomes such as other adverse events, service use or satisfaction with care, quality of life were not available. The evidence base around Zotepine is insufficient to provide firm conclusions on its absolute or relative effects. This is despite it being in use in Austria, France, Germany, Japan and the UK.