- Email: [email protected]
P.3.098 Addition of amisulpride to other atypical antipsychotics for treating resistant schizophrenia
$498
•
P3 Psychotic disorders and antipsychotics Aripiprazole versus risperidone in the treatment of acutely relapsed patients with schizophrenia in Taiwan: a randomized controlled trial
T.J. Hwang 1 *, H.Y. Chan 2, W.W. Lin 3, S.K. Lin 4, H.G. Hwu 1, M.Y. Cheng 5, R.A. Forbes 6. ]National Taiwan University
Hospital, Psychiatty, Taipei, Taiwan; 2 Taoyuan Psychiatric Centet; Psychiatty, Taiwan; 3Trisetvice General Hospital, Psychiatty, Taiwan; 4Taipei City Psychiatric Centet; Psychiatty, Taiwan; STalwart Otsuka Pharmaceutical Co., ClinicalResearch, Taiwan; 6princeton Aripiprazole Unit, ClinicalResearch, USA
References [1] Potkin, S.G., Saha, A.R., Kujawa, M.J., Carson, W.H., Ali, M., Stock, E., Stringfellow, J., Ingenito, G., Marder, S.R., 2003. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen PsychiatL2¢681 90.
•
Addition of amisulpride to other atypical antipsychotics for treating resistant schizophrenia
M.J. Merino Garcia*, C.G.J. Caballer Garcla. Servicios de Salud Mental del Principado de Asturias, Psychiatty, Gij6n, Spain
Purpose: This Phase IIIb, double-blind, randomized, multicenter
trial was designed to compare the efficacy and safety of aripiprazole and risperidone in the treatment of acutely relapsed Taiwanese patients with schizophrenia or schizoaffective disorder. M e t h o d s : Acutely relapsed patients, aged 18 60 years old, with DSM-IV diagnosis of schizophrenia or schizoaffective disorder were recruited and randomized to aripiprazole (15mg/day) or risperidone (6mg/day) with a 3:2 ratio. Efficacy (PANSS, CGI) and safety was monitored weekly for 4 weeks. Statistical analyses were based on intent-to-treat population with last observation carried forward. Results: A total of 95 patients were screened and 83 were randomized (49 in aripiprazole and 34 in risperidone group). Upon initial CGI assessment, patients were classified as severely ill (24%), markedly ill (46%), or moderately ill (28%). Regarding efficacy, treatment with aripiprazole or risperidone produced robust and clinically significant improvement, as observed on the PANSS-total, positive subscale, negative subscale and CGI-severity scores, with no statistical differences between 2 groups. Both groups demonstrated a rapid onset of action, with improvement by the end of week 1. Continued improvement was observed in the second, third and fourth week, with a 23.0% (aripiprazole group) and 24.9% (risperidone group) reduction in the PANSS-total at study endpoint. Regarding safety and tolerability, either aripiprazole or risperidone was, in general, well tolerated. Twenty-five percent of randomized patients discontinued treatment, with 10% due to adverse events (AEs). AEs were generally mild-to-moderate across both treatment groups. The most prevalent AE was insomnia (27%) in aripiprazole group, and extrapyramidal symptoms (EPS) (24%) in risperidone group. Hyperprolactinemia was reported in the risperidone group, with a mean change of serum prolactin level significantly different from that in the aripiprazole group at week 4 compared to baseline (55.4mg/dL for risperidone and 9.0mg/dL for aripiprazole). There was also a statistically significant change of EPS in the risperidone group compared to the aripiprazole group (+1.3 vs. 0.2, mean change from baseline as measured with SimpsonAngus Scale). Conclusions: Aripiprazole and risperidone treatment resulted in clinically significant improvement in Taiwanese patients with acute schizophrenia in this 4-week trial. The clinical improvement was noted in the first week, and there were no statistically significant differences in any efficacy measures between the 2 treatment groups along the course. In general, aripiprazole 15 mg/d was safe and well tolerated. In comparison, risperidone 6 mg/d was associated with significantly greater hyperprolactinemia and worsening of EPS.
S t a t e m e n t on the p u r p o s e of the study: A considerable percentage of schizophrenic patients (30 40% according to several authors) is resistant to monotherapy with atypical or conventional antipsychotics. Among the responders, more than 75% present some negative/positive residual symptoms. The objective of the study is to confirm the effectiveness of Amisulpride as add-on therapy to a previous atypical antipsychotic treatment. M e t h o d s used: This is a naturalistic observational study of 40 schizophrenic patients evaluated through PANSS-G and N and P subscales, CGI, DAI scale of attitude to the medication, analogical visual scale on health and the EuroQold-5D questionnaire of quality of life, before and after adding Amisulpride to a previous atypical antipsychotic treatment (Clozapine, Quetiapine, Risperidone or Ziprasidone). S u m m a r y of results a n d statistical assessments: With Amisulpride therapy, all patients show a clear and marked improvement both in the PANSS-G (change from percentile 50 to 5), and in the positive subscale (P50 to P5), as well as of general psychopatology (P50 to P5), but less marked in the negative subscale (P50 to P25). By items, delusions, hallucinations, suspicion and selfharm improve remarkably in the positive scale (75% reduction), and affective dullness and emotional seclusion in the negative subscale (75% improvement). In the PANSS-G scale, items improved as follows: motor tension (75%), unusual thoughts (75%), absence of insight (50%), control of impulses (75%) and active social avoidance (40%). The schizophrenic disorder evolves from positive (positive valence in the Composed scale, with 5 of real value) to negative (negative valence in the Composed scale with 3 of real value). All patients improved in the CGI (60%), in their perception of health (50% in the AVS), their attitude to the medication (65% of improvement in the DAI scale) and the quality of life improves by 60% in the measurements conducted with the EuroQold of 5 dimensions and in the vertical auto evaluation. To be remarked the improvement obtained in the anxiety/depression dimensions (80%), daily activities (75%) and self-care (80%). Conclusion: The antagonism potentiation D2-D3 offered by Amisulpride provides a valuable alternative in the treatment of schizophrenic patients with persistent symptoms.
References [1] Zink M, Henn F.A., Thome J. Combination of amisulpride and olanzapine in treatment resistant schizophrenic pychoses. European Psychiatry 2004; 19(1): 56 8. [2] Zink M, Knopf U., Henn F, Thome J. Combination of clozapine and amisulpride in treatment-resistant schizophrenia. Case reports and review of the literature. Pharmacopsychiatry 2004; 37:26 31. [3] Munro J., Matthiasson RD.C. Amisulpride augmentation of clozapine: an open non-randomized study in patients with schizophrenia partially responsive to clozapine. Acta Psychiatrica Scandinavica 2004; 110: 292298.
•
P3 Psychotic disorders and antipsychotics Aripiprazole versus risperidone in the treatment of acutely relapsed patients with schizophrenia in Taiwan: a randomized controlled trial
T.J. Hwang 1 *, H.Y. Chan 2, W.W. Lin 3, S.K. Lin 4, H.G. Hwu 1, M.Y. Cheng 5, R.A. Forbes 6. ]National Taiwan University
Hospital, Psychiatty, Taipei, Taiwan; 2 Taoyuan Psychiatric Centet; Psychiatty, Taiwan; 3Trisetvice General Hospital, Psychiatty, Taiwan; 4Taipei City Psychiatric Centet; Psychiatty, Taiwan; STalwart Otsuka Pharmaceutical Co., ClinicalResearch, Taiwan; 6princeton Aripiprazole Unit, ClinicalResearch, USA
References [1] Potkin, S.G., Saha, A.R., Kujawa, M.J., Carson, W.H., Ali, M., Stock, E., Stringfellow, J., Ingenito, G., Marder, S.R., 2003. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen PsychiatL2¢681 90.
•
Addition of amisulpride to other atypical antipsychotics for treating resistant schizophrenia
M.J. Merino Garcia*, C.G.J. Caballer Garcla. Servicios de Salud Mental del Principado de Asturias, Psychiatty, Gij6n, Spain
Purpose: This Phase IIIb, double-blind, randomized, multicenter
trial was designed to compare the efficacy and safety of aripiprazole and risperidone in the treatment of acutely relapsed Taiwanese patients with schizophrenia or schizoaffective disorder. M e t h o d s : Acutely relapsed patients, aged 18 60 years old, with DSM-IV diagnosis of schizophrenia or schizoaffective disorder were recruited and randomized to aripiprazole (15mg/day) or risperidone (6mg/day) with a 3:2 ratio. Efficacy (PANSS, CGI) and safety was monitored weekly for 4 weeks. Statistical analyses were based on intent-to-treat population with last observation carried forward. Results: A total of 95 patients were screened and 83 were randomized (49 in aripiprazole and 34 in risperidone group). Upon initial CGI assessment, patients were classified as severely ill (24%), markedly ill (46%), or moderately ill (28%). Regarding efficacy, treatment with aripiprazole or risperidone produced robust and clinically significant improvement, as observed on the PANSS-total, positive subscale, negative subscale and CGI-severity scores, with no statistical differences between 2 groups. Both groups demonstrated a rapid onset of action, with improvement by the end of week 1. Continued improvement was observed in the second, third and fourth week, with a 23.0% (aripiprazole group) and 24.9% (risperidone group) reduction in the PANSS-total at study endpoint. Regarding safety and tolerability, either aripiprazole or risperidone was, in general, well tolerated. Twenty-five percent of randomized patients discontinued treatment, with 10% due to adverse events (AEs). AEs were generally mild-to-moderate across both treatment groups. The most prevalent AE was insomnia (27%) in aripiprazole group, and extrapyramidal symptoms (EPS) (24%) in risperidone group. Hyperprolactinemia was reported in the risperidone group, with a mean change of serum prolactin level significantly different from that in the aripiprazole group at week 4 compared to baseline (55.4mg/dL for risperidone and 9.0mg/dL for aripiprazole). There was also a statistically significant change of EPS in the risperidone group compared to the aripiprazole group (+1.3 vs. 0.2, mean change from baseline as measured with SimpsonAngus Scale). Conclusions: Aripiprazole and risperidone treatment resulted in clinically significant improvement in Taiwanese patients with acute schizophrenia in this 4-week trial. The clinical improvement was noted in the first week, and there were no statistically significant differences in any efficacy measures between the 2 treatment groups along the course. In general, aripiprazole 15 mg/d was safe and well tolerated. In comparison, risperidone 6 mg/d was associated with significantly greater hyperprolactinemia and worsening of EPS.
S t a t e m e n t on the p u r p o s e of the study: A considerable percentage of schizophrenic patients (30 40% according to several authors) is resistant to monotherapy with atypical or conventional antipsychotics. Among the responders, more than 75% present some negative/positive residual symptoms. The objective of the study is to confirm the effectiveness of Amisulpride as add-on therapy to a previous atypical antipsychotic treatment. M e t h o d s used: This is a naturalistic observational study of 40 schizophrenic patients evaluated through PANSS-G and N and P subscales, CGI, DAI scale of attitude to the medication, analogical visual scale on health and the EuroQold-5D questionnaire of quality of life, before and after adding Amisulpride to a previous atypical antipsychotic treatment (Clozapine, Quetiapine, Risperidone or Ziprasidone). S u m m a r y of results a n d statistical assessments: With Amisulpride therapy, all patients show a clear and marked improvement both in the PANSS-G (change from percentile 50 to 5), and in the positive subscale (P50 to P5), as well as of general psychopatology (P50 to P5), but less marked in the negative subscale (P50 to P25). By items, delusions, hallucinations, suspicion and selfharm improve remarkably in the positive scale (75% reduction), and affective dullness and emotional seclusion in the negative subscale (75% improvement). In the PANSS-G scale, items improved as follows: motor tension (75%), unusual thoughts (75%), absence of insight (50%), control of impulses (75%) and active social avoidance (40%). The schizophrenic disorder evolves from positive (positive valence in the Composed scale, with 5 of real value) to negative (negative valence in the Composed scale with 3 of real value). All patients improved in the CGI (60%), in their perception of health (50% in the AVS), their attitude to the medication (65% of improvement in the DAI scale) and the quality of life improves by 60% in the measurements conducted with the EuroQold of 5 dimensions and in the vertical auto evaluation. To be remarked the improvement obtained in the anxiety/depression dimensions (80%), daily activities (75%) and self-care (80%). Conclusion: The antagonism potentiation D2-D3 offered by Amisulpride provides a valuable alternative in the treatment of schizophrenic patients with persistent symptoms.
References [1] Zink M, Henn F.A., Thome J. Combination of amisulpride and olanzapine in treatment resistant schizophrenic pychoses. European Psychiatry 2004; 19(1): 56 8. [2] Zink M, Knopf U., Henn F, Thome J. Combination of clozapine and amisulpride in treatment-resistant schizophrenia. Case reports and review of the literature. Pharmacopsychiatry 2004; 37:26 31. [3] Munro J., Matthiasson RD.C. Amisulpride augmentation of clozapine: an open non-randomized study in patients with schizophrenia partially responsive to clozapine. Acta Psychiatrica Scandinavica 2004; 110: 292298.