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Kinetics and safety of a novel risperidone depot formulation
198
B.61. K I N E T I C S A N D S A F E T Y O F A N O V E L RISPERIDONE DEPOT FORMULATIION M. Eerdekens, M. Rasmussen, A. Vermeulen, R. Lowenthal, A. Van Peer
Janssen Research Foundation, Turnhoutseweg 30, B-2340, Beerse, Belgium This study compared the bioavailability of a new intramuscular depot formulation and of oral doses of risperidone in patients with schizophrenia. Three groups of stable patients (N = 86) received oral risperidone (2, 4, or 6mg/day) during weeks 1 3 and oral risperidone at half those doses during weeks 4-5. During weeks 2 10, the three groups received depot doses of risperidone (25, 50, or 75mg, respectively) every 2 weeks (5 injections). Treatment with other antipsychotic medication in addition to the trial medication was allowed. Plasma concentrations of unchanged risperidone and of the active moiety (risperidone+9-hydroxyrisperidone) were determined. Adverse events, vital signs, and the injection site were evaluated regularly. Efficacy measures included the PANSS and CGI every two weeks. Total daily exposure to the active moiety was equivalent after oral and depot dosing: 90% confidence intervals for the mean steady state AUC and Cav ratio (depot vs. oral) were all within the bioequivalence range of 80% to 120%. Peak plasma concentrations were significantly lower (20% to 30%) after depot than oral dosing. Reported adverse events with the depot were not different from with oral risperidone. No consistent, clinically relevant changes in vital signs, ECG, or laboratory tests were observed. There was minor discomfort at the injection site in a few patients. Patients remained symptomatically stable (PANSS and CGI scores) when treatment was changed from an oral to a depot regimen. In conclusion, bioequivalence of oral and IM depot dosing of risperidone was demonstrated. Moreover, IM depot dosing was as well tolerated and efficacious as oral dosing.
B.62. R I S P E R I D O N E - O L A N Z A P I N E DRUG OUTCOME STUDIES IN SCHIZOPHRENIA (RODOS) SINGLE-CENTER REPORT FROM AN INTERNATIONAL STUDY SERIES A. Bille, J. A n d e r s e n
Psychiatric Hospital in Vordingborg, DK-4760 Vordingborg, Denmark This single center study is the first ro report the results of an international series of single-center studies comparing inpatient drug use patterns, costs, and outcomes associated with risperidone or olanzapine in a naturalistic clinical setting. Retrospective chart reviews of 68 patients with schizophrenia were conducted at the Vordinborg Hospital (Denmark). Data were collected from patients who were hospitalized for at least 120 days or who were discharged and for whom risperidone or
olanzapine was the drug of first choice for long-term pharmacologic treatment. Risperidone and olanzapine had similar efficacy (treatment was rated as effective in 77% vs 78%, respectively), but the median time to effective treatment was significantly shorter with risperidone (14 vs 19.5 days, P=0.04). Furthermore, 9 patients given olanzapine discontinued because of lack of efficacy or switched to other neuroleptics compared with 2 patients given risperidone (P=0.05). The mean daily doses were 3.1 mg of risperidone and 13.7 mg of olanzapine. The mean daily cost of olanzapine was significantly higher than that of risperidone (43.0 vs 14.0 DDK; P<0.001). The mean daily costs of all inpatient medications taken during the hospitalization were significantly higher in the olanzapine than risperidone patients (51.6 vs 22.9 DDK; P<0.001). Results from this study indicate that treatment with risperidone is more cost effective than treatment with olanzapine and shows efficacy earlier.
B.63. R I S P E R I D O N E VERSUS HALOPERIDOL FOR PREVENTION
OF
RELAPSE IN SCHIZOPHRENIA AND SCHIZOAFFECTIVE DISORDERS: LONGTERM DOUBLE-BLIND COMPARISON J. Csernansky, M D 1, A. O k a m o t o , ScD 2 1Metropolitan St, Louis Psychiatric Center, 5351 Delmar Blvd, St. Louis, Missouri 63112; 2janssen Research Foundation, 1125 Trenton-Harbourton Road, Titusville, New Jersey 08560
Purpose: A multicenter, randomized, double-blind comparison of risperidone (RIS) and haloperidol (HAL) in stable outpatient schizophrenics and patients with schizoaffective disorder was conducted to compare the time to relapse. Methods: Patients continued double-blind treatment until the last patient had completed 1 year. Assessments were made weekly for the first 4 weeks and at 4-week intervals thereafter. Scales used to assess efficacy included the total score on PANSS and all PANSS subscale scores. Safety evaluations included ESRS and clinical laboratory tests, including weight gain. Results: Of 365 treated patients in the trial, 41 (23.2%) in the RIS and 65 (34.6%) in the HAL groups relapsed by the end of the first year (P=0.009). During the entire trial, 45 (25.4%) patients on RIS and 75 (39.9%) patients on HAL relapsed (P=0.002). Patients in the RIS group experienced only a modest degree of weight gain (5.01bs at endpoint), a low rate of TD (0.6%), and a low rate of EPS. Conclusions: This study provides evidence for the long-term effectiveness of RIS and corroborates earlier pivotal trials in which RIS was found to be significantly superior to HAL against both positive and negative symptoms of schizophrenia. Previous short-term trials have shown RIS to be statistically superior to HAL in the control of positive and negative symptoms. This trial confirms the superior efficacy of RIS over HAL in long-term treatment. Patients treated with RIS also experienced a desirable safety profile in long-term treatment.
B.61. K I N E T I C S A N D S A F E T Y O F A N O V E L RISPERIDONE DEPOT FORMULATIION M. Eerdekens, M. Rasmussen, A. Vermeulen, R. Lowenthal, A. Van Peer
Janssen Research Foundation, Turnhoutseweg 30, B-2340, Beerse, Belgium This study compared the bioavailability of a new intramuscular depot formulation and of oral doses of risperidone in patients with schizophrenia. Three groups of stable patients (N = 86) received oral risperidone (2, 4, or 6mg/day) during weeks 1 3 and oral risperidone at half those doses during weeks 4-5. During weeks 2 10, the three groups received depot doses of risperidone (25, 50, or 75mg, respectively) every 2 weeks (5 injections). Treatment with other antipsychotic medication in addition to the trial medication was allowed. Plasma concentrations of unchanged risperidone and of the active moiety (risperidone+9-hydroxyrisperidone) were determined. Adverse events, vital signs, and the injection site were evaluated regularly. Efficacy measures included the PANSS and CGI every two weeks. Total daily exposure to the active moiety was equivalent after oral and depot dosing: 90% confidence intervals for the mean steady state AUC and Cav ratio (depot vs. oral) were all within the bioequivalence range of 80% to 120%. Peak plasma concentrations were significantly lower (20% to 30%) after depot than oral dosing. Reported adverse events with the depot were not different from with oral risperidone. No consistent, clinically relevant changes in vital signs, ECG, or laboratory tests were observed. There was minor discomfort at the injection site in a few patients. Patients remained symptomatically stable (PANSS and CGI scores) when treatment was changed from an oral to a depot regimen. In conclusion, bioequivalence of oral and IM depot dosing of risperidone was demonstrated. Moreover, IM depot dosing was as well tolerated and efficacious as oral dosing.
B.62. R I S P E R I D O N E - O L A N Z A P I N E DRUG OUTCOME STUDIES IN SCHIZOPHRENIA (RODOS) SINGLE-CENTER REPORT FROM AN INTERNATIONAL STUDY SERIES A. Bille, J. A n d e r s e n
Psychiatric Hospital in Vordingborg, DK-4760 Vordingborg, Denmark This single center study is the first ro report the results of an international series of single-center studies comparing inpatient drug use patterns, costs, and outcomes associated with risperidone or olanzapine in a naturalistic clinical setting. Retrospective chart reviews of 68 patients with schizophrenia were conducted at the Vordinborg Hospital (Denmark). Data were collected from patients who were hospitalized for at least 120 days or who were discharged and for whom risperidone or
olanzapine was the drug of first choice for long-term pharmacologic treatment. Risperidone and olanzapine had similar efficacy (treatment was rated as effective in 77% vs 78%, respectively), but the median time to effective treatment was significantly shorter with risperidone (14 vs 19.5 days, P=0.04). Furthermore, 9 patients given olanzapine discontinued because of lack of efficacy or switched to other neuroleptics compared with 2 patients given risperidone (P=0.05). The mean daily doses were 3.1 mg of risperidone and 13.7 mg of olanzapine. The mean daily cost of olanzapine was significantly higher than that of risperidone (43.0 vs 14.0 DDK; P<0.001). The mean daily costs of all inpatient medications taken during the hospitalization were significantly higher in the olanzapine than risperidone patients (51.6 vs 22.9 DDK; P<0.001). Results from this study indicate that treatment with risperidone is more cost effective than treatment with olanzapine and shows efficacy earlier.
B.63. R I S P E R I D O N E VERSUS HALOPERIDOL FOR PREVENTION
OF
RELAPSE IN SCHIZOPHRENIA AND SCHIZOAFFECTIVE DISORDERS: LONGTERM DOUBLE-BLIND COMPARISON J. Csernansky, M D 1, A. O k a m o t o , ScD 2 1Metropolitan St, Louis Psychiatric Center, 5351 Delmar Blvd, St. Louis, Missouri 63112; 2janssen Research Foundation, 1125 Trenton-Harbourton Road, Titusville, New Jersey 08560
Purpose: A multicenter, randomized, double-blind comparison of risperidone (RIS) and haloperidol (HAL) in stable outpatient schizophrenics and patients with schizoaffective disorder was conducted to compare the time to relapse. Methods: Patients continued double-blind treatment until the last patient had completed 1 year. Assessments were made weekly for the first 4 weeks and at 4-week intervals thereafter. Scales used to assess efficacy included the total score on PANSS and all PANSS subscale scores. Safety evaluations included ESRS and clinical laboratory tests, including weight gain. Results: Of 365 treated patients in the trial, 41 (23.2%) in the RIS and 65 (34.6%) in the HAL groups relapsed by the end of the first year (P=0.009). During the entire trial, 45 (25.4%) patients on RIS and 75 (39.9%) patients on HAL relapsed (P=0.002). Patients in the RIS group experienced only a modest degree of weight gain (5.01bs at endpoint), a low rate of TD (0.6%), and a low rate of EPS. Conclusions: This study provides evidence for the long-term effectiveness of RIS and corroborates earlier pivotal trials in which RIS was found to be significantly superior to HAL against both positive and negative symptoms of schizophrenia. Previous short-term trials have shown RIS to be statistically superior to HAL in the control of positive and negative symptoms. This trial confirms the superior efficacy of RIS over HAL in long-term treatment. Patients treated with RIS also experienced a desirable safety profile in long-term treatment.