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Safety and tolerability of aripiprazole in patients with schizophrenia stratified by race
18. Therapeutics: Treatment Trials
291
ESTROGEN TREATMENT IN WOMEN WITH SCHIZOPHRENIA: PSYCHOTIC SYMPTOM AND COGNITIVE RESPONSE J. Kulkarni,* S. White, A. de Castella, R Fitzgerald
Psychiatry, The Alfred/Monash University, Melbourne, V1C, Australia The actions of estrogen on dopaminergic and serotonergic neurotransmission are complex, but overall appear to mimic the actions of novel antipsychotics. Following our dose-finding study of adjunctive transdermal estradiol (a potent unconjugated form of estrogen) in women with acute schizophrenia (Kulkarni et al, 2001), we present results from an ongoing 28 day double-blind placebo controlled study of 100 microgram adjunctive estradiol in a total of 62 v~omen of child bearing age with acute schizophrenia. 35 women received adjunctive 100mcg transdermal estradiol, 27 women received transdermal placebo patch. Both groups received similar types and doses of antipsychotic medication (E2 group = mean 6.79mg risperidone equivalents compared with placebo group = 6.19mg risperidone equivalents. There was no significant difference in age, diagnoses or menstrual cycle phase between the groups. Mean baseline total PANSS scores for the estrogen group was 84.17 points compared with 72.78 for the placebo adjunct group. Using change from baseline measures our results showed that the estrogen group had a significantly greater improvement in psychotic symptoms with PANSS scores decreasing by 18.21 points compared with 3.14 point decrease in total PANSS score for placebo group (p < 0.005). Cognitive testing with Stroop, Digit Span, Visual Reproduction, Trails A and B, WMS, CVLT and COWAT was done in a subsample of 14 women (9 on estrogen, 5 on placebo). Preliminary data suggests improvement in verbal memory of the estrogen group over the trial. Hormone assays revealed significant increases in serum estrogen for the estrogen adjunct group with a corresponding significant decrease in luteinizing hormone. There were no significant side effects reported by the women in either group. In conclusion, this data strongly suggests that the addition of 100meg estradiol significantly improves the clinical outcome for women with acute schizophrenia in both their psychopathology and cognitive function. This work is supported by a grant from the Stanley Foundation, Washington, USA.
SAFETY AND TOLERABILITY OF ARIPIPRAZOLE IN PATIENTS WITH SCHIZOPHRENIA STRATIFIED BY RACE S. Lain,* W. H. Carson, E. Stock, R. Marcus, D. Archibald
Bristol-Myers Squibb, Plainsboro, N J, USA The objective of this study was to examine the safety and tolerability profile of aripiprazole in patients with different racial backgrounds. Data from short-term placebo-controlled studies of aripiprazole for treatment of schizophrenia or schizoaffective disorder were pooled and analyzed after stratifying patients by race. Of the 1339 patients who partieipated in these trials, 715 were White, 427 Black, 135 Hispanic, 31 Asian, and 31 were classified as Other. The small number of patient in the Hispanic, Asian, and Other categories makes meaningful interpretation of their AEs relative to the other racial groups difficuk. Generally, the safety and tolerability profile of aripiprazole in patient subgroups paralleled that in the overall patient population. The incidence of adverse events was low and similar to placebo in each racial group. For patients who received aripiprazole, the incidence of the EPS reported as an adverse event was higher among black patients than in white patients. However, other EPS-related adverse events (tremor and hypertonia) were reported less frequent-
ly in black patients than in white patients who received aripiprazole. The incidences of somnolence and insomnia were similar across all racial groups, while nausea and vomiting occurred with somewhat greater frequency among white patients than among black patients treated with aripiprazole. The efficacy of aripiprazole was similar in White and Black patients. In summary, no clinically important differences in the adverse event profile among racial groups have been identified. Aripiprazole appears to have a favorable safety and tolerability profile in all patients regardless of race.
DOES CONSTANT THERAPY INFER OPTIMAL EFFICACY IN SCHIZOPHRENIA? MOVING TO AN ADVANCED PHARMACOTHERAPEUTIC
OPTION R. Lasser,* C. Bossie, Y. Zhu, G. Gharabawi
CNS Medical Affairs, Janssen Pharmaceutica Products, Titusville, NJ, USA It is generally accepted that conventional depot antipsychotics provide constant pharmacological treatment, improving partial compliance and decreasing relapse compared to their oral counterparts. Atypical antipsychotics have improved safety and efficacy profiles, but currently available agents require dally dosing, a regimen commonly associated with partial compliance which can lead to symptom worsening and relapse. This analysis assessedpatients after switching from treatment with conventional depot antipsychotics to risperidone microspheres, the first long-acting injectable atypical antipsychotic. An open-label study was conducted with long-acting risperidone in stable patients with schizophrenia or schizoaffective disorder. Patients were assigned by clinician's judgment to 25, 50, or 75 mg long-acting risperidone every 2 weeks for 50 weeks (RIS-INT-57). One hundred eighty-eight (25.9%) patients were receiving conventional depot antipsychotics prior to the study. After switching to long-acting risperidone, mean Positive and Negative Syndrome Scale (PANSS) total scores improved significantly throughout the 50 weeks and at end point. Although patients were judged to be clinically stable at study entry, 51.5% realized clinical improvement defined as >d20% PANSS total score reduction, and 15.6% had a >d60% PANSS total score reduction. The severity of extrapyramidal symptoms improved after switching to long-acting risperidone (via Extrapyramidal Symptom Rating Scale [ESRS]). The ESRS subjective overall rating and physician rating of parkinsonism decreased significantly at each time point and at endpoint (p<0.001 ). The most common adverse events during the 50-weektrial were anxiety (28.7%), psychosis (19.2%), headache (18.1%), and insomnia (17.6%). These data show significant symptom improvement and a decrease in the severity of extrapyramidal symptoms following constant therapy with long-acting risperidone in stable patients previously receiving conventional depot antipsychotics. These results challenge the concept that constant therapy with currently available conventional depots provides optimal efficacy and support the use of a long-acting atypical for these patients.
EFFICACY AND SAFETY OF QUETIAPINE IN THE TREATMENT OF PATIENTS WITH SCHIZOPHRENIA IN KOREA H. Lee,* D.Y. Kang, D. H. Song, Y. S. Kim, D. I. Jon, S. J. Kim, Y. S. Kim, S. K. An Psychiatry, Severance Mental Health Hospital, Yonsei University College of Medicine, Gwangju-si, Gyeonggi-do, South Korea Aim: To assess the efficacy, tolerability and safety of quetiapine in the patients with schizophrenia, schizophreniform disorder, and
International Congress on Schizophrenia Research 2003
291
ESTROGEN TREATMENT IN WOMEN WITH SCHIZOPHRENIA: PSYCHOTIC SYMPTOM AND COGNITIVE RESPONSE J. Kulkarni,* S. White, A. de Castella, R Fitzgerald
Psychiatry, The Alfred/Monash University, Melbourne, V1C, Australia The actions of estrogen on dopaminergic and serotonergic neurotransmission are complex, but overall appear to mimic the actions of novel antipsychotics. Following our dose-finding study of adjunctive transdermal estradiol (a potent unconjugated form of estrogen) in women with acute schizophrenia (Kulkarni et al, 2001), we present results from an ongoing 28 day double-blind placebo controlled study of 100 microgram adjunctive estradiol in a total of 62 v~omen of child bearing age with acute schizophrenia. 35 women received adjunctive 100mcg transdermal estradiol, 27 women received transdermal placebo patch. Both groups received similar types and doses of antipsychotic medication (E2 group = mean 6.79mg risperidone equivalents compared with placebo group = 6.19mg risperidone equivalents. There was no significant difference in age, diagnoses or menstrual cycle phase between the groups. Mean baseline total PANSS scores for the estrogen group was 84.17 points compared with 72.78 for the placebo adjunct group. Using change from baseline measures our results showed that the estrogen group had a significantly greater improvement in psychotic symptoms with PANSS scores decreasing by 18.21 points compared with 3.14 point decrease in total PANSS score for placebo group (p < 0.005). Cognitive testing with Stroop, Digit Span, Visual Reproduction, Trails A and B, WMS, CVLT and COWAT was done in a subsample of 14 women (9 on estrogen, 5 on placebo). Preliminary data suggests improvement in verbal memory of the estrogen group over the trial. Hormone assays revealed significant increases in serum estrogen for the estrogen adjunct group with a corresponding significant decrease in luteinizing hormone. There were no significant side effects reported by the women in either group. In conclusion, this data strongly suggests that the addition of 100meg estradiol significantly improves the clinical outcome for women with acute schizophrenia in both their psychopathology and cognitive function. This work is supported by a grant from the Stanley Foundation, Washington, USA.
SAFETY AND TOLERABILITY OF ARIPIPRAZOLE IN PATIENTS WITH SCHIZOPHRENIA STRATIFIED BY RACE S. Lain,* W. H. Carson, E. Stock, R. Marcus, D. Archibald
Bristol-Myers Squibb, Plainsboro, N J, USA The objective of this study was to examine the safety and tolerability profile of aripiprazole in patients with different racial backgrounds. Data from short-term placebo-controlled studies of aripiprazole for treatment of schizophrenia or schizoaffective disorder were pooled and analyzed after stratifying patients by race. Of the 1339 patients who partieipated in these trials, 715 were White, 427 Black, 135 Hispanic, 31 Asian, and 31 were classified as Other. The small number of patient in the Hispanic, Asian, and Other categories makes meaningful interpretation of their AEs relative to the other racial groups difficuk. Generally, the safety and tolerability profile of aripiprazole in patient subgroups paralleled that in the overall patient population. The incidence of adverse events was low and similar to placebo in each racial group. For patients who received aripiprazole, the incidence of the EPS reported as an adverse event was higher among black patients than in white patients. However, other EPS-related adverse events (tremor and hypertonia) were reported less frequent-
ly in black patients than in white patients who received aripiprazole. The incidences of somnolence and insomnia were similar across all racial groups, while nausea and vomiting occurred with somewhat greater frequency among white patients than among black patients treated with aripiprazole. The efficacy of aripiprazole was similar in White and Black patients. In summary, no clinically important differences in the adverse event profile among racial groups have been identified. Aripiprazole appears to have a favorable safety and tolerability profile in all patients regardless of race.
DOES CONSTANT THERAPY INFER OPTIMAL EFFICACY IN SCHIZOPHRENIA? MOVING TO AN ADVANCED PHARMACOTHERAPEUTIC
OPTION R. Lasser,* C. Bossie, Y. Zhu, G. Gharabawi
CNS Medical Affairs, Janssen Pharmaceutica Products, Titusville, NJ, USA It is generally accepted that conventional depot antipsychotics provide constant pharmacological treatment, improving partial compliance and decreasing relapse compared to their oral counterparts. Atypical antipsychotics have improved safety and efficacy profiles, but currently available agents require dally dosing, a regimen commonly associated with partial compliance which can lead to symptom worsening and relapse. This analysis assessedpatients after switching from treatment with conventional depot antipsychotics to risperidone microspheres, the first long-acting injectable atypical antipsychotic. An open-label study was conducted with long-acting risperidone in stable patients with schizophrenia or schizoaffective disorder. Patients were assigned by clinician's judgment to 25, 50, or 75 mg long-acting risperidone every 2 weeks for 50 weeks (RIS-INT-57). One hundred eighty-eight (25.9%) patients were receiving conventional depot antipsychotics prior to the study. After switching to long-acting risperidone, mean Positive and Negative Syndrome Scale (PANSS) total scores improved significantly throughout the 50 weeks and at end point. Although patients were judged to be clinically stable at study entry, 51.5% realized clinical improvement defined as >d20% PANSS total score reduction, and 15.6% had a >d60% PANSS total score reduction. The severity of extrapyramidal symptoms improved after switching to long-acting risperidone (via Extrapyramidal Symptom Rating Scale [ESRS]). The ESRS subjective overall rating and physician rating of parkinsonism decreased significantly at each time point and at endpoint (p<0.001 ). The most common adverse events during the 50-weektrial were anxiety (28.7%), psychosis (19.2%), headache (18.1%), and insomnia (17.6%). These data show significant symptom improvement and a decrease in the severity of extrapyramidal symptoms following constant therapy with long-acting risperidone in stable patients previously receiving conventional depot antipsychotics. These results challenge the concept that constant therapy with currently available conventional depots provides optimal efficacy and support the use of a long-acting atypical for these patients.
EFFICACY AND SAFETY OF QUETIAPINE IN THE TREATMENT OF PATIENTS WITH SCHIZOPHRENIA IN KOREA H. Lee,* D.Y. Kang, D. H. Song, Y. S. Kim, D. I. Jon, S. J. Kim, Y. S. Kim, S. K. An Psychiatry, Severance Mental Health Hospital, Yonsei University College of Medicine, Gwangju-si, Gyeonggi-do, South Korea Aim: To assess the efficacy, tolerability and safety of quetiapine in the patients with schizophrenia, schizophreniform disorder, and
International Congress on Schizophrenia Research 2003