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P.3.c.001 Aripiprazole in schizophrenia: clinical, neuropsychological and biochemical aspects
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P.3.c Psychotic disorders and antipsychotics – Antipsychotics (clinical)
observed. His452Tyr polymorphism of the 5HT2A receptor gene was significantly associated with PANSS positive symptomatology at baseline. His/His homozygotes had higher scores within PANSS positive subscale than His/Tyr heterozygotes (p < 0.01). Significantly higher scores within positive symptomathology were observed in patients with His allele (p < 0.01). The relationship between baseline symptomathology measured with PANSS (total score, negative and general symptom subscores) and His452Tyr polymorphism was not statistically significant. No associations were observed between the other studied genetic variants of 5HT2A receptor gene and the level of psychopathology at the beginning of antipsychotic treatment. Conclusions: The results suggest that His452Tyr polymorphism of the 5HT2A receptor gene may influence the age of onset of schizophrenia. It may also be associated with the level of positive psychopathology during the acute psychotic episode. The presence of His allele may predispose to the earlier onset of psychosis and the course of psychotic episode that is chracterized with more severe initial psychopathology. References [1] Leboyer M, Bellivier F, Nosten-Bertrand M, Jouvent R, Pauls D, Mallet J, 1998, Psychiatric genetics: search for phenotypes. Trends Neurosci 221, 103–105.
P.3.c Psychotic disorders and antipsychotics – Antipsychotics (clinical) P.3.c.001 Aripiprazole in schizophrenia: clinical, neuropsychological and biochemical aspects W. Verhoeven1 ° , J.I.M. Egger2 , K.B.H. Ter Horst3 , D. Fekkes4 , S. Tuinier5 . 1 Vincent van Gogh Institute/Erasmus University Medical Centre, Department of Clinical Research/Department of Psychiatry, Venray/Rotterdam, The Netherlands; 2 Vincent van Gogh Institute for Psychiatry/Radboud University, Department of Clinical Research/Behavioural Science Institute, Venray/Nijmegen, The Netherlands; 3 Vincent van Gogh Institute for Psychiatry, Department of Residency Training, Venray, The Netherlands; 4 Erasmus University Medical Centre, Departments of Neuroscience and Psychiatry, Rotterdam, The Netherlands; 5 Vincent van Gogh Institute for Psychiatry, Department of Clinical Research, Venray, The Netherlands Introduction: The most recently introduced atypical antipsychotic is aripiprazole that may act as a dopamine modulating agent. Several studies have investigated the effects of atypical antipsychotics in comparison to classical compounds on cognition in schizophrenia. The rationale for such studies is the awareness that cognitive impairments are core features of schizophrenia. In general, a mild remediation of cognitive function is reported in favour of the novel compounds, although the dose of the reference compound haloperidol is mostly rather high. In the present paper the results of a practice based clinical trial with aripiprazole are presented and compared to published data on this compound. In addition, plasma amino acids and homovanillic acid (HVA) were measured as well as neurocognitive parameters. Methods: Patients in a subacute relapse of schizophrenia were enrolled in a baseline-controlled open prospective study of 14 weeks. Aripiprazole was administered in a starting dose of 15 mg daily.
Assessment of psychopathology was performed at baseline and weekly until week 8 and thereafter at week 12 and at endpoint (week 14) by means of the PANSS and the CGI-S. The primary efficacy measure was the percentage decrease on the BPRS total score. In addition, PANSS items most intrinsically related to cognitive function were summed to create a cognitive subscale of 9 items. A comprehensive neuropsychological assessment was performed at baseline and endpoint. Plasma concentrations of amino acids and HVA were measured at baseline and weeks 8 and 14 of treatment. Data analysis was performed on an intention-totreat basis (LOCF). Results: A total of 17 patients with DSM-IV paranoid type of schizophrenia was included of whom 1 dropped out shortly after baseline measurement because of withdrawal of informed consent. The mean daily dose at end point was 19 mg. Seven patients improved while 9 did not or even deteriorated. A significant improvement was observed on the CGI-S, PANSS total, PANSS neg and PANSS cogn. The percentage decrease on the BPRS total was only 16%. During treatment with aripiprazole there was only an improvement for the memory parameters immediate and delayed recall (baseline vs endpoint: p < 0.05). The mean concentration of glutamate was increased at baseline and decreased significantly towards endpoint. The mean HVA concentration at baseline was within normal range but increased significantly during treatment. So far 12 clinical trials have been published. They are difficult to understand because of the high levels of attrition, the lack of information on drop-outs and patients who respond to treatment, as well as the great variety in efficacy measures. Furthermore, there is no standardized predefined response criterium. The pooled data based on an intention-to-treat analysis show a response that varies between 15 and 20%. Conclusions: Although symptomatic improvement of the total group reached the level of significance on some rating scales, its clinical relevance is doubtful since the decrease was maximally 20% and the CGI-S scores demonstrate that the patients are still moderately ill or worse. The observed improvement in some aspects of memory function most probably coincides with the reduction of psychotic symptoms. References [1] El-Sayeh HG, Morganti C, 2006, Aripiprazole for schizophrenia. Cochrane Database Syst Rev 2: CD004578.
P.3.c.002 Comparative tolerability of rapid-acting intramuscular olanzapine and short-acting typical intramuscular antipsychotics D. Castle1 , D.H. Kwon2 , V. Novak3 , V. Pidrman4 , T. Udristoiu5 , I. Ruiz6 , H. McElroy7 , A. Lowry7 , M. Saylan8 , T. Treuer9 ° . 1 University of Melbourne, St Vincent’s Hospital, Melbourne, Australia; 2 National Bugok Hospital, Department of Psychiatry, Gyeongsangnam-do, South-Korea; 3 University of Ljubljana, Psychiatric Hospital, Ljubljana, Slovenia; 4 Palacky University Hospital, Department of Psychiatry, Olomouc, Czech Republic; 5 Neuropsychiatry Clinic, Department of Psychiatry, Craiova, Romania; 6 Eli Lilly and Company, Mexican Affiliate Medical Department, Mexico D.F., Mexico; 7 Eli Lilly Australia Pty Ltd, Intercontinental Information Sciences, Sydney, Australia; 8 Eli Lilly and Company, Turkish Affiliate Medical Department,
P.3.c Psychotic disorders and antipsychotics – Antipsychotics (clinical)
observed. His452Tyr polymorphism of the 5HT2A receptor gene was significantly associated with PANSS positive symptomatology at baseline. His/His homozygotes had higher scores within PANSS positive subscale than His/Tyr heterozygotes (p < 0.01). Significantly higher scores within positive symptomathology were observed in patients with His allele (p < 0.01). The relationship between baseline symptomathology measured with PANSS (total score, negative and general symptom subscores) and His452Tyr polymorphism was not statistically significant. No associations were observed between the other studied genetic variants of 5HT2A receptor gene and the level of psychopathology at the beginning of antipsychotic treatment. Conclusions: The results suggest that His452Tyr polymorphism of the 5HT2A receptor gene may influence the age of onset of schizophrenia. It may also be associated with the level of positive psychopathology during the acute psychotic episode. The presence of His allele may predispose to the earlier onset of psychosis and the course of psychotic episode that is chracterized with more severe initial psychopathology. References [1] Leboyer M, Bellivier F, Nosten-Bertrand M, Jouvent R, Pauls D, Mallet J, 1998, Psychiatric genetics: search for phenotypes. Trends Neurosci 221, 103–105.
P.3.c Psychotic disorders and antipsychotics – Antipsychotics (clinical) P.3.c.001 Aripiprazole in schizophrenia: clinical, neuropsychological and biochemical aspects W. Verhoeven1 ° , J.I.M. Egger2 , K.B.H. Ter Horst3 , D. Fekkes4 , S. Tuinier5 . 1 Vincent van Gogh Institute/Erasmus University Medical Centre, Department of Clinical Research/Department of Psychiatry, Venray/Rotterdam, The Netherlands; 2 Vincent van Gogh Institute for Psychiatry/Radboud University, Department of Clinical Research/Behavioural Science Institute, Venray/Nijmegen, The Netherlands; 3 Vincent van Gogh Institute for Psychiatry, Department of Residency Training, Venray, The Netherlands; 4 Erasmus University Medical Centre, Departments of Neuroscience and Psychiatry, Rotterdam, The Netherlands; 5 Vincent van Gogh Institute for Psychiatry, Department of Clinical Research, Venray, The Netherlands Introduction: The most recently introduced atypical antipsychotic is aripiprazole that may act as a dopamine modulating agent. Several studies have investigated the effects of atypical antipsychotics in comparison to classical compounds on cognition in schizophrenia. The rationale for such studies is the awareness that cognitive impairments are core features of schizophrenia. In general, a mild remediation of cognitive function is reported in favour of the novel compounds, although the dose of the reference compound haloperidol is mostly rather high. In the present paper the results of a practice based clinical trial with aripiprazole are presented and compared to published data on this compound. In addition, plasma amino acids and homovanillic acid (HVA) were measured as well as neurocognitive parameters. Methods: Patients in a subacute relapse of schizophrenia were enrolled in a baseline-controlled open prospective study of 14 weeks. Aripiprazole was administered in a starting dose of 15 mg daily.
Assessment of psychopathology was performed at baseline and weekly until week 8 and thereafter at week 12 and at endpoint (week 14) by means of the PANSS and the CGI-S. The primary efficacy measure was the percentage decrease on the BPRS total score. In addition, PANSS items most intrinsically related to cognitive function were summed to create a cognitive subscale of 9 items. A comprehensive neuropsychological assessment was performed at baseline and endpoint. Plasma concentrations of amino acids and HVA were measured at baseline and weeks 8 and 14 of treatment. Data analysis was performed on an intention-totreat basis (LOCF). Results: A total of 17 patients with DSM-IV paranoid type of schizophrenia was included of whom 1 dropped out shortly after baseline measurement because of withdrawal of informed consent. The mean daily dose at end point was 19 mg. Seven patients improved while 9 did not or even deteriorated. A significant improvement was observed on the CGI-S, PANSS total, PANSS neg and PANSS cogn. The percentage decrease on the BPRS total was only 16%. During treatment with aripiprazole there was only an improvement for the memory parameters immediate and delayed recall (baseline vs endpoint: p < 0.05). The mean concentration of glutamate was increased at baseline and decreased significantly towards endpoint. The mean HVA concentration at baseline was within normal range but increased significantly during treatment. So far 12 clinical trials have been published. They are difficult to understand because of the high levels of attrition, the lack of information on drop-outs and patients who respond to treatment, as well as the great variety in efficacy measures. Furthermore, there is no standardized predefined response criterium. The pooled data based on an intention-to-treat analysis show a response that varies between 15 and 20%. Conclusions: Although symptomatic improvement of the total group reached the level of significance on some rating scales, its clinical relevance is doubtful since the decrease was maximally 20% and the CGI-S scores demonstrate that the patients are still moderately ill or worse. The observed improvement in some aspects of memory function most probably coincides with the reduction of psychotic symptoms. References [1] El-Sayeh HG, Morganti C, 2006, Aripiprazole for schizophrenia. Cochrane Database Syst Rev 2: CD004578.
P.3.c.002 Comparative tolerability of rapid-acting intramuscular olanzapine and short-acting typical intramuscular antipsychotics D. Castle1 , D.H. Kwon2 , V. Novak3 , V. Pidrman4 , T. Udristoiu5 , I. Ruiz6 , H. McElroy7 , A. Lowry7 , M. Saylan8 , T. Treuer9 ° . 1 University of Melbourne, St Vincent’s Hospital, Melbourne, Australia; 2 National Bugok Hospital, Department of Psychiatry, Gyeongsangnam-do, South-Korea; 3 University of Ljubljana, Psychiatric Hospital, Ljubljana, Slovenia; 4 Palacky University Hospital, Department of Psychiatry, Olomouc, Czech Republic; 5 Neuropsychiatry Clinic, Department of Psychiatry, Craiova, Romania; 6 Eli Lilly and Company, Mexican Affiliate Medical Department, Mexico D.F., Mexico; 7 Eli Lilly Australia Pty Ltd, Intercontinental Information Sciences, Sydney, Australia; 8 Eli Lilly and Company, Turkish Affiliate Medical Department,