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P.3.124 Efficacy and tolerability of long-term (up to 5 years) open-label treatment with aripiprazole in schizophrenia
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P3 Psychotic disorders and antipsychotics Efficacy and tolerability of long-term (up to 5 years) open-label treatment with aripiprazole in schizophrenia
W. Carson 1 *, M. Ali 2, A. Saha 2, R. McQuade 3, R. Owen 4, E. Stock 4, Y. Yamamoto 5. ]Otsuka America Pharmaceutical
Inc, 3rd Floot; Princeton, USA; 20tsuka Matyland Research htstitute, Rockville, MD, USA; 30tsuka America Pharmaceutical htc, Princeton, NJ, USA; 4Bristol-Myers Squibb, Wallingford, CT, USA; 50tsuka Pharmaceutical Co. Ltd, Japan Purpose: To analyze the effects of aripiprazole treatment on measures of efficacy and tolerability in patients with schizophrenia for periods of up to 5 years using pooled data from long-term, open-label extension trials. Methods: Data from 639 patients with schizophrenia (639 at 1 year, 484 at 2 years, 385 at 3 years, 209 at 4 years and 55 at 5 years) in long-term, open-label extension trials with aripiprazole were pooled. Analysis was performed on efficacy (PANSS and CGI-severity) and tolerability parameters, including weight and laboratory values. Results: Efficacy was maintained over time, with improvement noted at each time point. The improvements in PANSS total score (baseline 73) at each time point were: 1 year 11; 2 years 13; 3 years 13; 4 years 15; 5 years 32. Weight gain was minimal over time, varying from increases of 1.9kg after 1 year to 6.7 kg after 5 years. There were no indications of increases in either total cholesterol or glucose levels over time, and no evidence of QTc prolongation emerged. Conclusion: Long-term exposure to aripiprazole appeared to result in maintenance of effect, with improvement of symptoms over time. No late-emerging tolerability issues were identified and aripiprazole continued to be well tolerated.
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Plasma homovanillic acid levels and short-term outcome in first episode shizophrenia
I. Baeza 1 *, V. Sfinchiez-Gistau2, J. Castro 1, E. De la Serna 1, R. Deulofeu 3, M. Bernardo 4. ]Hospital Clinic, Childhood
and Adolescent Psychiatty Department, Barcelona, Spain; 2Hospital Clinic, Psychiatry Department, Spain; 3Hospital Clinic, Biochemistty Department, Spain; 4Hospital Clinic, Psychiatty, Spain AIM: To study the relationship between pHVA levels measured at different times and the outcome after one year of follow up in first episode schizophrenic patients. Methods: A sample of 34 first episode schizophrenic patients (diagnosed according DSM-IV criteria) were observed for a year after first admission. Patients were 19 male, 15 female, aged 15 30 (mean:21.48 ±4.9 years). All were naive of neuroleptics before entering the study and treated with risperidone to homogenize the sample (mean dose at day 28:6.32±1.75 mg/day), pHVA and psychopathology were measured before the antipsychotic treatment and after 2, 4, 7, 14, and 28 days, three and twelve months. Psychopatology was evaluated by BPRS, SAPS and SANS. Global functioning with GAF was also assessed, pHVA was analyzed by High Performance Liquid Chromatography (HPLC) with electrochemical detection, following the method described by Chang et al (1983). SPSS statistical package was used to analize the data, with Student-t test and Pearson correlation test as main test used to compare the results.
Results: 19 patients finished the follow-up period with the same antipsychotic treatment, four patients were lost during the follow-up, and 11 patients were changed from risperidone to another treatment. In the 19-patient sample, baseline pHVA (mean: 20.42±11.87 and after one year of treatment was not statistically significant. Baseline compared to one year assessment psychopathology ratings were statistically significant for all the scales (p > 0.05). pHVA at day 4 had a weak statistically significant correlation (r 0.48, p 0.061) with SAPS total score at one year assessment. Other correlations between pHVA levels and symptomatology and GAF scale at 1 year assessment were not statistically significant. Conclusions: pHVA at baseline and after initiating treatment with risperidone was not related to one year outcome in our sample of first-episode schizophrenia except for a tendency between higher pHVA levels at day 4 and lower SAPS score at one year assessment. It would be important to increase the sample size in our study to confirm this tendency. Previous studies reported high pHVA levels as useful predictors of outcome in shorterterm neuroleptic treatment (four or five weeks)(Pickar et al, 1984, Davila et al, 1997). These results must be distinguished from our study because of the different time frame used to assess short-term outcome.
References [1] Davila R, Zumarraga M, Andia I, Almoguera-Abad A, Friedhoff AJ, Early increase of plasma HVA during neuroleptic treatment: a tool for outcome prediction and for subtyping of schizophrenia. In: Plasma Homovanillic in schizophrenia. Implication for presynaptic dopamine dysfunction. Edited by American Psychiatric Press, Washington DC, 1997. Pags, 8%101. [2] Perez V, Catafau AM, Corripio I, Martin JC, Alvarez E, Preliminary evidence of striatal D2 receptor density as a possible biological marker of prognosis in naive schizophrenic patients. Progr Neuro Psychopharmacol Biol Psychiatry 2003; 27:767 70. [3] Pickar D, Labarca R, Linnoila M, Roy A, Hommer D, Everett D, Paul SM, Neuroleptic-induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenic patients. Science 1984; 225: 54 7.
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Intramuscular aripiprazole and Iorazepam vs. placebo for agitation in acute mania
D. Kostic 1 *, D. Oren 2, R. Marcus 2, S. Vanveggel3, W. Carson 4, R. McQuade 4, G. Manos 2. ]Bristol Myers Squibb, Lawrenceville,
USA; 2Bristol-Myers Squibb, Wallingford, CT, USA; 3BristolMyers Squibb, Braine-l'Alleud, Belgium; 40tsuka America Pharmaceutical Inc, Princeton, NJ, USA Purpose: A comparison of the efficacy of intramuscular (IM) aripiprazole and IM lorazepam with placebo in the treatment of acutely agitated patients with a manic or mixed episode in bipolar I disorder. Methods: This double-blind, randomized, multicenter study compared two doses of IM aripiprazole (10mg and 15mg), lorazepam (2mg), and placebo in a total of 291 patients. The first injection was followed by inpatient evaluation for 24 hours. If needed, a second injection was given ~> 2 hours post-initial injection and a third injection, if needed, ~>2 hours post-second injection. The primary efficacy measure was the mean change from baseline to 2 hours (LOCF) in the PANSS Excited Component (PEC) score after the initial IM injection. Results: Mean changes from baseline in PEC scores 2 hours post-initial IM injection were: aripiprazole 10mg (n 75), 8.7; aripiprazole 15mg (n 75), 8.7; lorazepam 2 m g (n 68), 9.6,
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P3 Psychotic disorders and antipsychotics Efficacy and tolerability of long-term (up to 5 years) open-label treatment with aripiprazole in schizophrenia
W. Carson 1 *, M. Ali 2, A. Saha 2, R. McQuade 3, R. Owen 4, E. Stock 4, Y. Yamamoto 5. ]Otsuka America Pharmaceutical
Inc, 3rd Floot; Princeton, USA; 20tsuka Matyland Research htstitute, Rockville, MD, USA; 30tsuka America Pharmaceutical htc, Princeton, NJ, USA; 4Bristol-Myers Squibb, Wallingford, CT, USA; 50tsuka Pharmaceutical Co. Ltd, Japan Purpose: To analyze the effects of aripiprazole treatment on measures of efficacy and tolerability in patients with schizophrenia for periods of up to 5 years using pooled data from long-term, open-label extension trials. Methods: Data from 639 patients with schizophrenia (639 at 1 year, 484 at 2 years, 385 at 3 years, 209 at 4 years and 55 at 5 years) in long-term, open-label extension trials with aripiprazole were pooled. Analysis was performed on efficacy (PANSS and CGI-severity) and tolerability parameters, including weight and laboratory values. Results: Efficacy was maintained over time, with improvement noted at each time point. The improvements in PANSS total score (baseline 73) at each time point were: 1 year 11; 2 years 13; 3 years 13; 4 years 15; 5 years 32. Weight gain was minimal over time, varying from increases of 1.9kg after 1 year to 6.7 kg after 5 years. There were no indications of increases in either total cholesterol or glucose levels over time, and no evidence of QTc prolongation emerged. Conclusion: Long-term exposure to aripiprazole appeared to result in maintenance of effect, with improvement of symptoms over time. No late-emerging tolerability issues were identified and aripiprazole continued to be well tolerated.
•
Plasma homovanillic acid levels and short-term outcome in first episode shizophrenia
I. Baeza 1 *, V. Sfinchiez-Gistau2, J. Castro 1, E. De la Serna 1, R. Deulofeu 3, M. Bernardo 4. ]Hospital Clinic, Childhood
and Adolescent Psychiatty Department, Barcelona, Spain; 2Hospital Clinic, Psychiatry Department, Spain; 3Hospital Clinic, Biochemistty Department, Spain; 4Hospital Clinic, Psychiatty, Spain AIM: To study the relationship between pHVA levels measured at different times and the outcome after one year of follow up in first episode schizophrenic patients. Methods: A sample of 34 first episode schizophrenic patients (diagnosed according DSM-IV criteria) were observed for a year after first admission. Patients were 19 male, 15 female, aged 15 30 (mean:21.48 ±4.9 years). All were naive of neuroleptics before entering the study and treated with risperidone to homogenize the sample (mean dose at day 28:6.32±1.75 mg/day), pHVA and psychopathology were measured before the antipsychotic treatment and after 2, 4, 7, 14, and 28 days, three and twelve months. Psychopatology was evaluated by BPRS, SAPS and SANS. Global functioning with GAF was also assessed, pHVA was analyzed by High Performance Liquid Chromatography (HPLC) with electrochemical detection, following the method described by Chang et al (1983). SPSS statistical package was used to analize the data, with Student-t test and Pearson correlation test as main test used to compare the results.
Results: 19 patients finished the follow-up period with the same antipsychotic treatment, four patients were lost during the follow-up, and 11 patients were changed from risperidone to another treatment. In the 19-patient sample, baseline pHVA (mean: 20.42±11.87 and after one year of treatment was not statistically significant. Baseline compared to one year assessment psychopathology ratings were statistically significant for all the scales (p > 0.05). pHVA at day 4 had a weak statistically significant correlation (r 0.48, p 0.061) with SAPS total score at one year assessment. Other correlations between pHVA levels and symptomatology and GAF scale at 1 year assessment were not statistically significant. Conclusions: pHVA at baseline and after initiating treatment with risperidone was not related to one year outcome in our sample of first-episode schizophrenia except for a tendency between higher pHVA levels at day 4 and lower SAPS score at one year assessment. It would be important to increase the sample size in our study to confirm this tendency. Previous studies reported high pHVA levels as useful predictors of outcome in shorterterm neuroleptic treatment (four or five weeks)(Pickar et al, 1984, Davila et al, 1997). These results must be distinguished from our study because of the different time frame used to assess short-term outcome.
References [1] Davila R, Zumarraga M, Andia I, Almoguera-Abad A, Friedhoff AJ, Early increase of plasma HVA during neuroleptic treatment: a tool for outcome prediction and for subtyping of schizophrenia. In: Plasma Homovanillic in schizophrenia. Implication for presynaptic dopamine dysfunction. Edited by American Psychiatric Press, Washington DC, 1997. Pags, 8%101. [2] Perez V, Catafau AM, Corripio I, Martin JC, Alvarez E, Preliminary evidence of striatal D2 receptor density as a possible biological marker of prognosis in naive schizophrenic patients. Progr Neuro Psychopharmacol Biol Psychiatry 2003; 27:767 70. [3] Pickar D, Labarca R, Linnoila M, Roy A, Hommer D, Everett D, Paul SM, Neuroleptic-induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenic patients. Science 1984; 225: 54 7.
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Intramuscular aripiprazole and Iorazepam vs. placebo for agitation in acute mania
D. Kostic 1 *, D. Oren 2, R. Marcus 2, S. Vanveggel3, W. Carson 4, R. McQuade 4, G. Manos 2. ]Bristol Myers Squibb, Lawrenceville,
USA; 2Bristol-Myers Squibb, Wallingford, CT, USA; 3BristolMyers Squibb, Braine-l'Alleud, Belgium; 40tsuka America Pharmaceutical Inc, Princeton, NJ, USA Purpose: A comparison of the efficacy of intramuscular (IM) aripiprazole and IM lorazepam with placebo in the treatment of acutely agitated patients with a manic or mixed episode in bipolar I disorder. Methods: This double-blind, randomized, multicenter study compared two doses of IM aripiprazole (10mg and 15mg), lorazepam (2mg), and placebo in a total of 291 patients. The first injection was followed by inpatient evaluation for 24 hours. If needed, a second injection was given ~> 2 hours post-initial injection and a third injection, if needed, ~>2 hours post-second injection. The primary efficacy measure was the mean change from baseline to 2 hours (LOCF) in the PANSS Excited Component (PEC) score after the initial IM injection. Results: Mean changes from baseline in PEC scores 2 hours post-initial IM injection were: aripiprazole 10mg (n 75), 8.7; aripiprazole 15mg (n 75), 8.7; lorazepam 2 m g (n 68), 9.6,