- Email: [email protected]
Safety and tolerability of aripiprazole at doses higher than 30 mg
P2. Psychotic disorders and antipsychotics
$288
References [1] Bromel T, Blum WF, Ziegler A e t al. Serum leptin levels increase rapidly after initiation of clozapine therapy. Moleculer Psychiatry 1998; 3:76-80 [2] Kraus T, Haack M, Schuld Aet al. body weight and leptin plasma levels during treatment wth antipsychotic drugs. A J Psychiatry 1999; 156:312-314
•
Aripiprazole versus placebo for relapse prevention in patients with chronic schizophrenia
W Carson 1, R. McQuade 2, A. Saha 3, A. Torbeyns4, E. Stock 1.
1Bristol-Myers Squibb, Wallingford, U.S.A.; eBristol-Myers Squibb, Lawrenceuille, U.S.A.; 30tsuka Maryland Research Institute, LLC, Rockville, U.S.A.; 4Bristol-Myers Squibb, Waterloo, Belgium Objective: To assess relapse prevention with aripiprazole compared to placebo over 26 weeks in patients with chronic, stable schizophrenia. Methods: A mnlticenter, randomized, double-blind, placebocontrolled study was conducted in 310 patients with chronic schizophrenia considered stable (no significant improvement or worsening in last 3 months; baseline PANSS=82) randomized to aripiprazole 15 rag/day or placebo. Efficacy measures included time-to-relapse, number of relapses and PANSS total score. Results: Compared to placebo, treatment with aripiprazole was shown to be effective in increasing time-to-relapse, and resulted in significantly fewer patients relapsing at endpoint versus placebo (34% vs. 57%, respectively). Aripiprazole treatment resulted in significantly greater improvement in PANSS total score and PANSS positive subscale score, compared to placebo. Patients on both aripiprazole and placebo showed improvement on the PANSS negative subscale score. Aripiprazole was generally well tolerated with an adverse event profile comparable to placebo. No clinically significant changes occurred in SAS, AIMS, or Barnes Akathisia scores in either group. There were no elevations in plasma prolactin levels with aripiprazole compared to placebo. No clinically important cardiac risks were associated with aripiprazole. Weight gain associated with aripiprazole was comparable to placebo. Conclusion: Aripiprazole was demonstrated to increase the time to and decrease the rate of relapse in patients with chronic schizophrenia, with a favorable safety and tolerability profile, representing an important addition to the current antipsychotic armamentarium.
•
Aripiprazole for long-term maintenance treatment of schizophrenia
R. McQuade ° , W. Carson 2, A. Saha 3, G. Ingenito3, M. Ali3, D. Archibald2. 1Bristol-Myers Squibb, Lawrenceville, U.S.A.;
2Bristol-Myers Squibb, Wallingford, U.S.A.; 30tsuka Maryland Research Institute, LLC, Rockville, U.S.A. Objective: To evaluate the maintenance of effect and longterm efficacy, safety and tolerability of aripiprazole, a dopamineserotonin system stabilizer, compared to haloperidol when administered for 52 weeks. Methods: A multicenter, randomized, double-blind study was conducted in 1,294 patients with acute relapse of chronic schizophrenia randomized to aripiprazole 30 mg (n=861) or haloperidol
10 mg (n=433) daily. A one-time dose reduction was allowed to aripiprazole 20 mg and haloperidol 7 mg. Efficacy evaluations included PANSS and MADRS scores. Results: Aripiprazole demonstrated significantly greater response rates than did haloperidol (62.4% vs. 54.9%). In addition, aripiprazole was associated with significantly lower discontinuation rates than haloperidol. Aripiprazole produced statistically significant improvements in the PANSS negative subscale score at Weeks 26 and 52 (both p<0.03). Aripiprazole also demonstrated statistically significant improvement from baseline in depressive symptoms as shown in the MADRS scores at Weeks 8, 26, and 52, compared to haloperidol (all p<0.03). The discontinuation rate due to an adverse event was significantly lower in the aripiprazole group than in the haloperidol group (p<0.001). The overall incidence of EPS-related adverse events was significantly lower with aripiprazole than with haloperidol (p<0.001). Both treatments resulted in comparable weight gain. There was no significant difference in QTc interval between groups. Conclusion: Aripiprazole may represent the next-generation antipsychotic leading to increased compliance in schizophrenia due to significantly greater improvements in negative and depressive symptoms, and a superior safety and tolerability profile compared to haloperidol.
•
Safety and tolerability of aripiprazole at doses higher than 30 mg
P. Auby 1, A. Saha 2, M. Ali2, G. Ingenito2, R. Wilber3, S. Bramer2. 1Bristol-Myers Squibb, Waterloo, Belgium; eOtsuka
Maryland Research Institute, LLC, Rockville, U.S.A.; 3BristolMyers Squibb, Wallingford, U.S.A. Objective: To evaluate the safety, tolerability, and pharmacokinetics of escalating doses of aripiprazole from 30 mg to 90 mg/day. Methods: A randomized, double-blind, parallel-group, inpatient, pilot study was conducted in 40 patients with stable schizophrenia or schizoaffective disorder (mean baseline PANSS of 4364) randomized to aripiprazole 30 mg/day (control for each dosing group, n=12), 45 mg/day (n=7), 60 mg/day (n=7), 75 mg/day (n=7), or 90 rag/day (n=7) for more than 15 days for each dose. Results: There were no clinically significant changes from baseline in SAS, AIMS, and Barnes Akathisia scores across all groups. There was an increased incidence of akathisia and tachycardia in the 90 mg dose group; however, there were no discontinuations due to adverse events in this group. There was no dose-dependent increase in weight. There were no clinically relevant ECG changes and no significant changes in prolactin levels. Plasma concentrations of aripiprazole and its metabolites increased proportionately with dose. Patients in all dose groups maintained a stable symptom profile, based on PANSS total score, PANSS positive and negative subscale scores, and the CGI Severity of Illness Score. Conclusion: Aripiprazole is safe and well tolerated at doses of 30 mg to 90 rag/day. Escalating doses of aripiprazole demonstrated linear pharmacokinetics following multiple doses and consistent control of schizophrenic symptoms.
$288
References [1] Bromel T, Blum WF, Ziegler A e t al. Serum leptin levels increase rapidly after initiation of clozapine therapy. Moleculer Psychiatry 1998; 3:76-80 [2] Kraus T, Haack M, Schuld Aet al. body weight and leptin plasma levels during treatment wth antipsychotic drugs. A J Psychiatry 1999; 156:312-314
•
Aripiprazole versus placebo for relapse prevention in patients with chronic schizophrenia
W Carson 1, R. McQuade 2, A. Saha 3, A. Torbeyns4, E. Stock 1.
1Bristol-Myers Squibb, Wallingford, U.S.A.; eBristol-Myers Squibb, Lawrenceuille, U.S.A.; 30tsuka Maryland Research Institute, LLC, Rockville, U.S.A.; 4Bristol-Myers Squibb, Waterloo, Belgium Objective: To assess relapse prevention with aripiprazole compared to placebo over 26 weeks in patients with chronic, stable schizophrenia. Methods: A mnlticenter, randomized, double-blind, placebocontrolled study was conducted in 310 patients with chronic schizophrenia considered stable (no significant improvement or worsening in last 3 months; baseline PANSS=82) randomized to aripiprazole 15 rag/day or placebo. Efficacy measures included time-to-relapse, number of relapses and PANSS total score. Results: Compared to placebo, treatment with aripiprazole was shown to be effective in increasing time-to-relapse, and resulted in significantly fewer patients relapsing at endpoint versus placebo (34% vs. 57%, respectively). Aripiprazole treatment resulted in significantly greater improvement in PANSS total score and PANSS positive subscale score, compared to placebo. Patients on both aripiprazole and placebo showed improvement on the PANSS negative subscale score. Aripiprazole was generally well tolerated with an adverse event profile comparable to placebo. No clinically significant changes occurred in SAS, AIMS, or Barnes Akathisia scores in either group. There were no elevations in plasma prolactin levels with aripiprazole compared to placebo. No clinically important cardiac risks were associated with aripiprazole. Weight gain associated with aripiprazole was comparable to placebo. Conclusion: Aripiprazole was demonstrated to increase the time to and decrease the rate of relapse in patients with chronic schizophrenia, with a favorable safety and tolerability profile, representing an important addition to the current antipsychotic armamentarium.
•
Aripiprazole for long-term maintenance treatment of schizophrenia
R. McQuade ° , W. Carson 2, A. Saha 3, G. Ingenito3, M. Ali3, D. Archibald2. 1Bristol-Myers Squibb, Lawrenceville, U.S.A.;
2Bristol-Myers Squibb, Wallingford, U.S.A.; 30tsuka Maryland Research Institute, LLC, Rockville, U.S.A. Objective: To evaluate the maintenance of effect and longterm efficacy, safety and tolerability of aripiprazole, a dopamineserotonin system stabilizer, compared to haloperidol when administered for 52 weeks. Methods: A multicenter, randomized, double-blind study was conducted in 1,294 patients with acute relapse of chronic schizophrenia randomized to aripiprazole 30 mg (n=861) or haloperidol
10 mg (n=433) daily. A one-time dose reduction was allowed to aripiprazole 20 mg and haloperidol 7 mg. Efficacy evaluations included PANSS and MADRS scores. Results: Aripiprazole demonstrated significantly greater response rates than did haloperidol (62.4% vs. 54.9%). In addition, aripiprazole was associated with significantly lower discontinuation rates than haloperidol. Aripiprazole produced statistically significant improvements in the PANSS negative subscale score at Weeks 26 and 52 (both p<0.03). Aripiprazole also demonstrated statistically significant improvement from baseline in depressive symptoms as shown in the MADRS scores at Weeks 8, 26, and 52, compared to haloperidol (all p<0.03). The discontinuation rate due to an adverse event was significantly lower in the aripiprazole group than in the haloperidol group (p<0.001). The overall incidence of EPS-related adverse events was significantly lower with aripiprazole than with haloperidol (p<0.001). Both treatments resulted in comparable weight gain. There was no significant difference in QTc interval between groups. Conclusion: Aripiprazole may represent the next-generation antipsychotic leading to increased compliance in schizophrenia due to significantly greater improvements in negative and depressive symptoms, and a superior safety and tolerability profile compared to haloperidol.
•
Safety and tolerability of aripiprazole at doses higher than 30 mg
P. Auby 1, A. Saha 2, M. Ali2, G. Ingenito2, R. Wilber3, S. Bramer2. 1Bristol-Myers Squibb, Waterloo, Belgium; eOtsuka
Maryland Research Institute, LLC, Rockville, U.S.A.; 3BristolMyers Squibb, Wallingford, U.S.A. Objective: To evaluate the safety, tolerability, and pharmacokinetics of escalating doses of aripiprazole from 30 mg to 90 mg/day. Methods: A randomized, double-blind, parallel-group, inpatient, pilot study was conducted in 40 patients with stable schizophrenia or schizoaffective disorder (mean baseline PANSS of 4364) randomized to aripiprazole 30 mg/day (control for each dosing group, n=12), 45 mg/day (n=7), 60 mg/day (n=7), 75 mg/day (n=7), or 90 rag/day (n=7) for more than 15 days for each dose. Results: There were no clinically significant changes from baseline in SAS, AIMS, and Barnes Akathisia scores across all groups. There was an increased incidence of akathisia and tachycardia in the 90 mg dose group; however, there were no discontinuations due to adverse events in this group. There was no dose-dependent increase in weight. There were no clinically relevant ECG changes and no significant changes in prolactin levels. Plasma concentrations of aripiprazole and its metabolites increased proportionately with dose. Patients in all dose groups maintained a stable symptom profile, based on PANSS total score, PANSS positive and negative subscale scores, and the CGI Severity of Illness Score. Conclusion: Aripiprazole is safe and well tolerated at doses of 30 mg to 90 rag/day. Escalating doses of aripiprazole demonstrated linear pharmacokinetics following multiple doses and consistent control of schizophrenic symptoms.