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William H. Carson - One of the best experts on this subject based on the ideXlab platform.

  • Aripiprazole once monthly for treatment of schizophrenia double blind randomised non inferiority study
    British Journal of Psychiatry, 2014
    Co-Authors: Wolfgang W Fleischhacker, Robert D Mcquade, Ross A Baker, Raymond Sanchez, Pamela Perry, Na Jin, Timothy Petersstrickland, B Johnson, Anna Eramo, William H. Carson
    Abstract:

    Background Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents. Aims To assess the efficacy of Aripiprazole once-monthly compared with oral Aripiprazole for maintenance treatment of schizophrenia. Method A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to Aripiprazole once-monthly 400 mg, oral Aripiprazole (10-30 mg/day) or Aripiprazole once-monthly 50 mg (a dose below the therapeutic threshold for assay sensitivity). (Trial registration: [clinicaltrials.gov][1], [NCT00706654][2].) Results A total of 1118 patients were screened, and 662 responders to oral Aripiprazole were randomised. Kaplan-Meier estimated impending relapse rates at week 26 were 7.12% for Aripiprazole once-monthly 400 mg and 7.76% for oral Aripiprazole. This difference (–0.64%, 95% CI –5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments were superior to Aripiprazole once-monthly 50 mg (21.80%, P ⩽0.001). Conclusions Aripiprazole once-monthly 400 mg was non-inferior to oral Aripiprazole, and the reduction in Kaplan-Meier estimated impending relapse rate at week 26 was statistically significant v. Aripiprazole once-monthly 50 mg. [1]: http://clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00706654&atom=%2Fbjprcpsych%2Fearly%2F2014%2F05%2F23%2Fbjp.bp.113.134213.atom

  • pharmacokinetics tolerability and safety of Aripiprazole once monthly in adult schizophrenia an open label parallel arm multiple dose study
    Schizophrenia Research, 2013
    Co-Authors: Suresh Mallikaarjun, Robert D Mcquade, William H. Carson, Raymond Sanchez, John M Kane, Patricia Bricmont, Robert A Forbes, Wolfgang W Fleischhacker
    Abstract:

    This 24-week, open-label, Phase Ib, parallel-arm, multiple-dose trial assessed the pharmacokinetics, safety and tolerability of a once-monthly injection of Aripiprazole (Aripiprazole once-monthly) in 41 subjects with schizophrenia. The objective was to determine if Aripiprazole plasma concentrations (at doses of 200, 300 and 400mg) were within the therapeutic range observed for the oral tablet (10-30 mg). Completion rates were 36.4% (n=4/11), 50.0% (n=8/16) and 71.4% (n=10/14) for the 200mg, 300 mg and 400mg groups, respectively. Patients were stabilized on oral Aripiprazole (10mg/day) before the first injection and received oral Aripiprazole (10mg/day) concomitantly with the first dose of Aripiprazole once-monthly for 14 days. Administration of Aripiprazole once-monthly at doses of 300 and 400mg provided sustained mean Aripiprazole plasma concentrations comparable with the concentration range observed following multiple consecutive daily doses of oral Aripiprazole. In contrast, plasma concentrations following administration of Aripiprazole once-monthly at a dose of 200mg were below the therapeutic range and pharmacokinetic parameters were not proportional to the administered dose compared with the 300 mg and 400mg doses. Treatment with Aripiprazole once-monthly, at any dose, did not result in any clinically meaningful changes from baseline in extrapyramidal symptom scales, clinical laboratory tests, vital signs, or electrocardiogram parameters. The most common treatment-emergent adverse events were vomiting (13.3%, 300 mg; 14.3%, 400mg), injection site pain (28.6%, 400mg), upper respiratory tract infection (10%, 200mg; 6.7% 300 mg; 14.3%, 400mg) and tremor (6.7%, 300 mg; 21.4%, 400mg). In conclusion, Aripiprazole once-monthly at doses of 300 and 400mg is a viable formulation for treatment of adults with schizophrenia.

  • Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia a 52 week multicenter randomized double blind placebo controlled study
    The Journal of Clinical Psychiatry, 2012
    Co-Authors: John M Kane, Robert D Mcquade, William H. Carson, Raymond Sanchez, Pamela Perry, Na Jin, B Johnson, Robert A Forbes, Wolfgang W Fleischhacker
    Abstract:

    OBJECTIVE: To evaluate the efficacy and tolerability of a once-monthly intramuscular (IM) depot formulation of the dopamine partial agonist Aripiprazole as maintenance treatment in adults meeting DSM-IV-TR schizophrenia criteria. METHOD: The study was conducted from July 2008 until February 2011. Subjects requiring chronic treatment with an antipsychotic entered a 4- to 12-week oral stabilization phase and received oral Aripiprazole (10-30 mg/d). Subjects meeting stability criteria for 4 weeks entered an IM-depot stabilization phase in which they received 400-mg Aripiprazole-IM-depot injections every 4 weeks (single decrease to 300 mg permitted) with coadministration of oral Aripiprazole tablets in the first 2 weeks. Subjects meeting stability criteria for 12 consecutive weeks were randomly assigned (2:1) to Aripiprazole-IM-depot or placebo during a 52-week, double-blind maintenance phase. The primary outcome measure was time to exacerbation of psychotic symptoms/impending relapse (event). Safety and tolerability were also assessed. RESULTS: 710 patients entered oral stabilization, 576 progressed to IM-depot stabilization, and 403 were randomly assigned to double-blind treatment. The study was terminated early because efficacy was demonstrated by the preplanned interim analysis (conducted after 64 events). Time to impending relapse was significantly delayed with Aripiprazole-IM-depot treatment compared with placebo in both the interim analysis and the final analysis (P < .0001, log-rank test). The hazard ratio (placebo/Aripiprazole-IM-depot) at final analysis was 5.03 (95% CI, 3.15-8.02). The rate of impending relapse was significantly lower with Aripiprazole-IM-depot than placebo at endpoint (final analysis, 10.0% [n = 27/269] vs 39.6% [n = 53/134]). Improvements in Clinical Global Impressions-Severity of Illness scale and Positive and Negative Syndrome Scale total scores were maintained with Aripiprazole-IM-depot treatment but showed significant worsening with placebo (change from double-blind baseline, P < .0001 for Aripiprazole-IM-depot vs placebo). The most common treatment-emergent adverse events (occurring in ≥ 5% of Aripiprazole-IM-depot subjects and greater than placebo) were insomnia, tremor, and headache. CONCLUSIONS: Aripiprazole-IM-depot significantly delayed time to impending relapse compared with placebo and appears to be a well-tolerated maintenance treatment option for schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00705783.

  • Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.
    Pediatrics, 2009
    Co-Authors: Randall Owen, Robert D Mcquade, Ronald N Marcus, William H. Carson, George Manos, Linmarie Sikich, Patricia K. Corey-lisle, Robert L. Findling
    Abstract:

    OBJECTIVE: The objective of this study was to evaluate short-term efficacy and safety of Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these. METHODS: This 8-week, double-blind, randomized, placebo-controlled, parallel-group study was conducted of children and adolescents (aged 6–17 years) with autistic disorder. Patients were randomly assigned (1:1) to flexibly dosed Aripiprazole (target dosage: 5, 10, or 15 mg/day) or placebo. Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression–Improvement score (CGI-I). Safety and tolerability were also assessed. RESULTS: Ninety-eight patients were randomly assigned to receive placebo (n = 51) or Aripiprazole (n = 47). Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with Aripiprazole than with placebo from week 1 through week 8. Aripiprazole demonstrated significantly greater global improvements than placebo, as assessed by the mean CGI-I score from week 1 through week 8; however, clinically significant residual symptoms may still persist for some patients. Discontinuation rates as a result of adverse events (AEs) were 10.6% for Aripiprazole and 5.9% for placebo. Extrapyramidal symptom-related AE rates were 14.9% for Aripiprazole and 8.0% for placebo. No serious AEs were reported. Mean weight gain was 2.0 kg on Aripiprazole and 0.8 kg on placebo at week 8. CONCLUSIONS: Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated.

  • acute treatment of pediatric bipolar i disorder manic or mixed episode with Aripiprazole a randomized double blind placebo controlled study
    The Journal of Clinical Psychiatry, 2009
    Co-Authors: Robert L. Findling, Robert D Mcquade, William H. Carson, Na Jin, Robert A Forbes, Margaretta Nyilas, Taro Iwamoto, Svetlana Ivanova, Kiki D Chang
    Abstract:

    OBJECTIVES To determine the efficacy and safety of Aripiprazole for the treatment of pediatric bipolar I disorder, manic or mixed episode, with or without psychotic features. METHOD Subjects were enrolled between March 2005 and February 2007 in a randomized, multicenter, double-blind 4-week study of Aripiprazole 10 mg/d, Aripiprazole 30 mg/d, and placebo. Subjects (n = 296) were 10 to 17 years old with a DSM-IV diagnosis of bipolar I disorder with current manic or mixed episodes, with or without psychotic features, and a Young Mania Rating Scale (YMRS) score > or = 20. The primary efficacy variable was change from baseline in the YMRS total score. RESULTS Both doses of Aripiprazole were superior to placebo on the YMRS total score beginning at week 1 and continuing through week 4. Aripiprazole 10 mg and 30 mg were more effective than placebo on global improvement, mania, and overall bipolar illness outcome measures. Response ( > or = 50% reduction in YMRS total score) at week 4 was achieved by 44.8%, 63.6%, and 26.1% of subjects in the Aripiprazole 10 mg, Aripiprazole 30 mg, and placebo groups, respectively (P < .01 both doses vs placebo). Both doses were generally well tolerated. The most common adverse events were extrapyramidal disorder and somnolence; rates were higher for Aripiprazole 30 mg compared with Aripiprazole 10 mg. Average weight gain was not significantly different between the Aripiprazole 10 mg (+0.82 kg) or 30 mg (+1.08 kg) groups compared with the placebo group (+0.56 kg) (P = .35 and P = .13, respectively). CONCLUSIONS Aripiprazole in daily doses of 10 mg or 30 mg is an effective and generally well-tolerated acute treatment for pediatric subjects with bipolar I mania or mixed episodes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00110461.

Robert D Mcquade - One of the best experts on this subject based on the ideXlab platform.

  • Aripiprazole once monthly for treatment of schizophrenia double blind randomised non inferiority study
    British Journal of Psychiatry, 2014
    Co-Authors: Wolfgang W Fleischhacker, Robert D Mcquade, Ross A Baker, Raymond Sanchez, Pamela Perry, Na Jin, Timothy Petersstrickland, B Johnson, Anna Eramo, William H. Carson
    Abstract:

    Background Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents. Aims To assess the efficacy of Aripiprazole once-monthly compared with oral Aripiprazole for maintenance treatment of schizophrenia. Method A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to Aripiprazole once-monthly 400 mg, oral Aripiprazole (10-30 mg/day) or Aripiprazole once-monthly 50 mg (a dose below the therapeutic threshold for assay sensitivity). (Trial registration: [clinicaltrials.gov][1], [NCT00706654][2].) Results A total of 1118 patients were screened, and 662 responders to oral Aripiprazole were randomised. Kaplan-Meier estimated impending relapse rates at week 26 were 7.12% for Aripiprazole once-monthly 400 mg and 7.76% for oral Aripiprazole. This difference (–0.64%, 95% CI –5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments were superior to Aripiprazole once-monthly 50 mg (21.80%, P ⩽0.001). Conclusions Aripiprazole once-monthly 400 mg was non-inferior to oral Aripiprazole, and the reduction in Kaplan-Meier estimated impending relapse rate at week 26 was statistically significant v. Aripiprazole once-monthly 50 mg. [1]: http://clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00706654&atom=%2Fbjprcpsych%2Fearly%2F2014%2F05%2F23%2Fbjp.bp.113.134213.atom

  • pharmacokinetics tolerability and safety of Aripiprazole once monthly in adult schizophrenia an open label parallel arm multiple dose study
    Schizophrenia Research, 2013
    Co-Authors: Suresh Mallikaarjun, Robert D Mcquade, William H. Carson, Raymond Sanchez, John M Kane, Patricia Bricmont, Robert A Forbes, Wolfgang W Fleischhacker
    Abstract:

    This 24-week, open-label, Phase Ib, parallel-arm, multiple-dose trial assessed the pharmacokinetics, safety and tolerability of a once-monthly injection of Aripiprazole (Aripiprazole once-monthly) in 41 subjects with schizophrenia. The objective was to determine if Aripiprazole plasma concentrations (at doses of 200, 300 and 400mg) were within the therapeutic range observed for the oral tablet (10-30 mg). Completion rates were 36.4% (n=4/11), 50.0% (n=8/16) and 71.4% (n=10/14) for the 200mg, 300 mg and 400mg groups, respectively. Patients were stabilized on oral Aripiprazole (10mg/day) before the first injection and received oral Aripiprazole (10mg/day) concomitantly with the first dose of Aripiprazole once-monthly for 14 days. Administration of Aripiprazole once-monthly at doses of 300 and 400mg provided sustained mean Aripiprazole plasma concentrations comparable with the concentration range observed following multiple consecutive daily doses of oral Aripiprazole. In contrast, plasma concentrations following administration of Aripiprazole once-monthly at a dose of 200mg were below the therapeutic range and pharmacokinetic parameters were not proportional to the administered dose compared with the 300 mg and 400mg doses. Treatment with Aripiprazole once-monthly, at any dose, did not result in any clinically meaningful changes from baseline in extrapyramidal symptom scales, clinical laboratory tests, vital signs, or electrocardiogram parameters. The most common treatment-emergent adverse events were vomiting (13.3%, 300 mg; 14.3%, 400mg), injection site pain (28.6%, 400mg), upper respiratory tract infection (10%, 200mg; 6.7% 300 mg; 14.3%, 400mg) and tremor (6.7%, 300 mg; 21.4%, 400mg). In conclusion, Aripiprazole once-monthly at doses of 300 and 400mg is a viable formulation for treatment of adults with schizophrenia.

  • Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia a 52 week multicenter randomized double blind placebo controlled study
    The Journal of Clinical Psychiatry, 2012
    Co-Authors: John M Kane, Robert D Mcquade, William H. Carson, Raymond Sanchez, Pamela Perry, Na Jin, B Johnson, Robert A Forbes, Wolfgang W Fleischhacker
    Abstract:

    OBJECTIVE: To evaluate the efficacy and tolerability of a once-monthly intramuscular (IM) depot formulation of the dopamine partial agonist Aripiprazole as maintenance treatment in adults meeting DSM-IV-TR schizophrenia criteria. METHOD: The study was conducted from July 2008 until February 2011. Subjects requiring chronic treatment with an antipsychotic entered a 4- to 12-week oral stabilization phase and received oral Aripiprazole (10-30 mg/d). Subjects meeting stability criteria for 4 weeks entered an IM-depot stabilization phase in which they received 400-mg Aripiprazole-IM-depot injections every 4 weeks (single decrease to 300 mg permitted) with coadministration of oral Aripiprazole tablets in the first 2 weeks. Subjects meeting stability criteria for 12 consecutive weeks were randomly assigned (2:1) to Aripiprazole-IM-depot or placebo during a 52-week, double-blind maintenance phase. The primary outcome measure was time to exacerbation of psychotic symptoms/impending relapse (event). Safety and tolerability were also assessed. RESULTS: 710 patients entered oral stabilization, 576 progressed to IM-depot stabilization, and 403 were randomly assigned to double-blind treatment. The study was terminated early because efficacy was demonstrated by the preplanned interim analysis (conducted after 64 events). Time to impending relapse was significantly delayed with Aripiprazole-IM-depot treatment compared with placebo in both the interim analysis and the final analysis (P < .0001, log-rank test). The hazard ratio (placebo/Aripiprazole-IM-depot) at final analysis was 5.03 (95% CI, 3.15-8.02). The rate of impending relapse was significantly lower with Aripiprazole-IM-depot than placebo at endpoint (final analysis, 10.0% [n = 27/269] vs 39.6% [n = 53/134]). Improvements in Clinical Global Impressions-Severity of Illness scale and Positive and Negative Syndrome Scale total scores were maintained with Aripiprazole-IM-depot treatment but showed significant worsening with placebo (change from double-blind baseline, P < .0001 for Aripiprazole-IM-depot vs placebo). The most common treatment-emergent adverse events (occurring in ≥ 5% of Aripiprazole-IM-depot subjects and greater than placebo) were insomnia, tremor, and headache. CONCLUSIONS: Aripiprazole-IM-depot significantly delayed time to impending relapse compared with placebo and appears to be a well-tolerated maintenance treatment option for schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00705783.

  • efficacy of adjunctive Aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy
    International Clinical Psychopharmacology, 2012
    Co-Authors: James Craig Nelson, Michael E Thase, Elizabeth E Bellocchio, Linda Rollin, James M Eudicone, Robert D Mcquade, Ronald N Marcus, Robert M Berman, Ross A Baker
    Abstract:

    To evaluate the efficacy of adjunctive Aripiprazole in patients with minimal response to prior antidepressant therapy (ADT). Pooled data from three randomized, double-blind, placebo-controlled studies assessing the efficacy of adjunctive Aripiprazole to ADT in patients with major depressive disorder who had a minimal response [< 25% reduction on the Montgomery-Asberg Depression Rating Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind adjunctive phase, response was defined as at least 50% reduction in the MADRS score and remission as at least 50% reduction in MADRS score and a MADRS score ≤ 10. Rates were examined using analysis of covariance and Cochran-Mantel-Haenszel tests. Kaplan-Meier curves were used to calculate time to response and remission. Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal responder). Time to response and remission were significantly shorter for ADT minimal responders receiving Aripiprazole+ADT versus adjunctive placebo+ADT. ADT minimal responders on Aripiprazole+ADT showed significantly greater improvements in MADRS score at endpoint compared with minimal responders on placebo+ADT (-10.3 vs. -6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly higher response rates with Aripiprazole+ADT than placebo+ADT (36 vs. 19%, respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively, P<0.0001). The numbers needed to treat with Aripiprazole+ADT were six for response and eight for remission. Aripiprazole augmentation had a rapid and clinically meaningful effect in ADT minimal responders.

  • evaluation of akathisia in patients with schizophrenia schizoaffective disorder or bipolar i disorder a post hoc analysis of pooled data from short and long term Aripiprazole trials
    Journal of Psychopharmacology, 2010
    Co-Authors: John M Kane, James M Eudicone, Robert D Mcquade, Thomas R E Barnes, Christoph U Correll, Gary S Sachs, Peter F Buckley, Quynh Van Tran, Andrei Pikalov, Sheila Assuncaotalbott
    Abstract:

    The objective of this article is to assess the clinical characteristics of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder receiving Aripiprazole, haloperidol, olanzapine, or placebo. We conducted post hoc analyses of pooled safety data from trials in patients with schizophrenia, schizoaffective disorder, and bipolar I disorder. Outcome measures included the incidence of akathisia, time to onset, duration, severity, and discontinuation due to akathisia, concomitant use of benzodiazepines and/or anticholinergics, Barnes Akathisia Rating Scale (BARS) scores, and the correlation between antipsychotic efficacy and akathisia. The results for schizophrenia and schizoaffective disorder were as follows: akathisia in 9% of Aripiprazole- and 6% of placebo-treated patients; 12.5% of Aripiprazole- versus 24% of haloperidol-treated patients; 11% of Aripiprazole- versus 6% of olanzapine-treated patients. Bipolar I disorder: akathisia in 18% of Aripiprazole- and 5% of placebo-treated patients. The clinical characteristics of akathisia were similar between each data set, regardless of disease. Akathisia was generally mild-to-moderate in severity. Discontinuation due to akathisia was low in both the schizophrenia trials (Aripiprazole 0.3%; placebo 0%; Aripiprazole 0.9%; haloperidol 2.3%; Aripiprazole 1.2%; olanzapine 0.2%) and the bipolar trials (Aripiprazole 2.3%; placebo 0%). Treatment-emergent akathisia was not associated with a poorer clinical response. In conclusion, akathisia with Aripiprazole occurred early in treatment, was mild-to-moderate in severity, led to few study discontinuations, and did not compromise therapeutic efficacy.

Ronald N Marcus - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of adjunctive Aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy
    International Clinical Psychopharmacology, 2012
    Co-Authors: James Craig Nelson, Michael E Thase, Elizabeth E Bellocchio, Linda Rollin, James M Eudicone, Robert D Mcquade, Ronald N Marcus, Robert M Berman, Ross A Baker
    Abstract:

    To evaluate the efficacy of adjunctive Aripiprazole in patients with minimal response to prior antidepressant therapy (ADT). Pooled data from three randomized, double-blind, placebo-controlled studies assessing the efficacy of adjunctive Aripiprazole to ADT in patients with major depressive disorder who had a minimal response [< 25% reduction on the Montgomery-Asberg Depression Rating Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind adjunctive phase, response was defined as at least 50% reduction in the MADRS score and remission as at least 50% reduction in MADRS score and a MADRS score ≤ 10. Rates were examined using analysis of covariance and Cochran-Mantel-Haenszel tests. Kaplan-Meier curves were used to calculate time to response and remission. Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal responder). Time to response and remission were significantly shorter for ADT minimal responders receiving Aripiprazole+ADT versus adjunctive placebo+ADT. ADT minimal responders on Aripiprazole+ADT showed significantly greater improvements in MADRS score at endpoint compared with minimal responders on placebo+ADT (-10.3 vs. -6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly higher response rates with Aripiprazole+ADT than placebo+ADT (36 vs. 19%, respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively, P<0.0001). The numbers needed to treat with Aripiprazole+ADT were six for response and eight for remission. Aripiprazole augmentation had a rapid and clinically meaningful effect in ADT minimal responders.

  • Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.
    Pediatrics, 2009
    Co-Authors: Randall Owen, Robert D Mcquade, Ronald N Marcus, William H. Carson, George Manos, Linmarie Sikich, Patricia K. Corey-lisle, Robert L. Findling
    Abstract:

    OBJECTIVE: The objective of this study was to evaluate short-term efficacy and safety of Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these. METHODS: This 8-week, double-blind, randomized, placebo-controlled, parallel-group study was conducted of children and adolescents (aged 6–17 years) with autistic disorder. Patients were randomly assigned (1:1) to flexibly dosed Aripiprazole (target dosage: 5, 10, or 15 mg/day) or placebo. Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression–Improvement score (CGI-I). Safety and tolerability were also assessed. RESULTS: Ninety-eight patients were randomly assigned to receive placebo (n = 51) or Aripiprazole (n = 47). Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with Aripiprazole than with placebo from week 1 through week 8. Aripiprazole demonstrated significantly greater global improvements than placebo, as assessed by the mean CGI-I score from week 1 through week 8; however, clinically significant residual symptoms may still persist for some patients. Discontinuation rates as a result of adverse events (AEs) were 10.6% for Aripiprazole and 5.9% for placebo. Extrapyramidal symptom-related AE rates were 14.9% for Aripiprazole and 8.0% for placebo. No serious AEs were reported. Mean weight gain was 2.0 kg on Aripiprazole and 0.8 kg on placebo at week 8. CONCLUSIONS: Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated.

  • Aripiprazole monotherapy in acute mania 12 week randomised placebo and haloperidol controlled study
    British Journal of Psychiatry, 2009
    Co-Authors: Allan H Young, Robert D Mcquade, Ronald N Marcus, William H. Carson, Anne Torbeyns, Dan A Oren, Adam Lowy, Nina H Spiller, Raymond Sanchez
    Abstract:

    Background Well-tolerated and effective therapies for bipolar mania are required. Aims To evaluate the efficacy and tolerability of Aripiprazole as acute and maintenance of effect therapy in patients with bipolar I disorder experiencing manic or mixed episodes. Method Patients were randomised to double-blind Aripiprazole (15 or 30 mg/day; n =167), placebo ( n =153) or haloperidol (5–15 mg/day, n =165) for 3 weeks (trial registration [NCT00097266][1]). Aripiprazole- and haloperidol-treated patients remained on masked treatment for 9 additional weeks. Results Mean change in Young Mania Rating Scale Total score (primary end-point) at week 3 was significantly greater with Aripiprazole (–12.0; P <0.05) and haloperidol (–12.8; P <0.01) than with placebo (–9.7). Improvements were maintained to week 12 for Aripiprazole (–17.2) and haloperidol (–17.8). Aripiprazole was well tolerated. Extrapyramidal adverse events were more frequent with haloperidol than Aripiprazole (53.3% v . 23.5%). Conclusions Clinical improvements with Aripiprazole were sustained to week 12. Aripiprazole was generally well tolerated. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00097266&atom=%2Fbjprcpsych%2F194%2F1%2F40.atom

  • a multicenter randomized double blind study of the effects of Aripiprazole in overweight subjects with schizophrenia or schizoaffective disorder switched from olanzapine
    The Journal of Clinical Psychiatry, 2008
    Co-Authors: John W Newcomer, Ronald N Marcus, Robert M Berman, Joao Alberto De Oliveira Campos, Christopher D Breder, Wendy Kerselaers, Gilbert Litalien, Marleen Nys, William H. Carson
    Abstract:

    Objective: Major mental disorders are associated with an increased risk for obesity-related cardiovascular mortality, leading to interest in risk-reduction approaches that target weight and risk-related plasma lipids, including use of antipsychotic agents with low metabolic risk. This multicenter, randomized, double-blind study compared the metabolic effects of Aripiprazole versus olanzapine in overweight persons with schizophrenia or schizoaffective disorder who were previously on olanzapine treatment. Method: In total, 173 subjects with DSM-IV-TR-defined schizophrenia or schizoaffective disorder were randomly assigned to receive Aripiprazole (N = 88) or olanzapine (N = 85) for 16 weeks in a study conducted from March 30, 2004, to August 8, 2006. Primary and secondary endpoints were mean weight change from baseline and percentage change from baseline in fasting triglyceride levels, respectively. Results: At week 16, weight decreased significantly with Aripiprazole versus olanzapine (-1.8 vs. +1.41 kg; p <.001). Significant differences in percentage change in triglyceride levels were observed with Aripiprazole (decreases) versus olanzapine (increases) at all time-points. In addition, significantly more subjects receiving Aripiprazole had clinically relevant (≥ 7%) weight loss versus olanzapine (11.1% vs. 2.6%; p =.038), and a lower percentage of subjects receiving Aripiprazole had clinically relevant weight gain (2.5% vs. 9.1%; p =.082). Mean percentage changes in fasting total cholesterol and high-density lipoprotein cholesterol at week 16 were significantly different with Aripiprazole versus olanzapine, with no significant effects on glycemic laboratory measures. Mean Clinical Global Impressions-Improvement (CGI-I) scores for both groups were in the range of "no change" to "minimal improvement." CGI-I endpoint scores were statistically significantly better with olanzapine (mean ± SE = 3.09 ± 0.16) versus Aripiprazole (mean ± SE = 3.74 ± 0.15; p <.001), and more subjects discontinued Aripiprazole (N = 32/88; 36%) than olanzapine (N = 22/85; 26%). Conclusion: Significant improvements in weight and lipids observed during discontinuation of olanzapine and switch to Aripiprazole treatment occurred with limited evidence of negative psychiatric effects, relative to uninterrupted continuation of olanzapine treatment. The results suggest that the potential value of therapeutic substitutions involving specific antipsychotic medications should be considered in overall efforts to reduce cardiovascular risk in this population.

  • Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, double-blind study versus placebo.
    The Journal of clinical psychiatry, 2007
    Co-Authors: Paul E. Keck, James M Eudicone, Robert D Mcquade, Ronald N Marcus, Joseph R. Calabrese, Roger S. Mcintyre, William H. Carson, Berit X. Carlson, Raymond Sanchez
    Abstract:

    Objective: A 26-week, double-blind, placebo-controlled relapse prevention study of Aripiprazole was designed a priori with a prospective, 74-week, double-blind, placebo-controlled extension phase. Efficacy and tolerability of Aripiprazole for relapse prevention in bipolar I disorder was, therefore, evaluated for 100 weeks. Method: Patients with DSM-IV bipolar I disorder, recent manic or mixed episode, received open-label Aripiprazole 15 or 30 mg/day (started at 30 mg/day) for 6 to 18 weeks. Patients achieving stabilization (Young Mania Rating Scale score ≤ 10 and Montgomery-Asberg Depression Rating Scale score ≤13 for 6 consecutive weeks) entered the double-blind phase, at which point they were randomly assigned to double-blind treatment with Aripiprazole or placebo for 26 weeks. The primary endpoint was time to relapse for any mood episode. Patients who completed the 26-week stabilization continued in a double-blind fashion with Aripiprazole or placebo for an additional 74 weeks and were monitored for relapse, efficacy, and tolerability. The study was conducted from March 2000 to June 2003. Results: In total, 161 patients met the stabilization criteria and were randomly assigned to Aripiprazole (N = 78) or placebo (N = 83). At 100 weeks, time to relapse was significantly longer with Aripiprazole (N = 7) than placebo (N = 5; hazard ratio = 0.53 [p =.011; 95% CI = 0.32 to 0.87]); however, a further 24 patients had discontinued due to study closure. Aripiprazole was superior to placebo in delaying time to manic relapse (p =.005; hazard ratio = 0.35 [95% CI = 0.16 to 0.75]); however, no significant differences were observed in time to depressive relapse (p =.602; hazard ratio = 0.81 [95% CI = 0.36 to 1.81]). The adverse events reported during 100 weeks of treatment with Aripiprazole versus placebo (≥ 5% incidence and twice placebo rate) were tremor, akathisia, dry mouth, hypertension, weight gain, vaginitis, abnormal thinking, pharyngitis, and flu syndrome. Mean weight change from baseline to 100 weeks (last observation carried forward) was +0.4 ± 0.8 kg with Aripiprazole and -1.9 ± 0.8 kg with placebo. Conclusions: Over a 100-week treatment period, Aripiprazole monotherapy was effective for relapse prevention in patients who were initially stabilized on Aripiprazole for 6 consecutive weeks, and it maintained a good safety and tolerability profile.

Raymond Sanchez - One of the best experts on this subject based on the ideXlab platform.

  • Aripiprazole once monthly for treatment of schizophrenia double blind randomised non inferiority study
    British Journal of Psychiatry, 2014
    Co-Authors: Wolfgang W Fleischhacker, Robert D Mcquade, Ross A Baker, Raymond Sanchez, Pamela Perry, Na Jin, Timothy Petersstrickland, B Johnson, Anna Eramo, William H. Carson
    Abstract:

    Background Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents. Aims To assess the efficacy of Aripiprazole once-monthly compared with oral Aripiprazole for maintenance treatment of schizophrenia. Method A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to Aripiprazole once-monthly 400 mg, oral Aripiprazole (10-30 mg/day) or Aripiprazole once-monthly 50 mg (a dose below the therapeutic threshold for assay sensitivity). (Trial registration: [clinicaltrials.gov][1], [NCT00706654][2].) Results A total of 1118 patients were screened, and 662 responders to oral Aripiprazole were randomised. Kaplan-Meier estimated impending relapse rates at week 26 were 7.12% for Aripiprazole once-monthly 400 mg and 7.76% for oral Aripiprazole. This difference (–0.64%, 95% CI –5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments were superior to Aripiprazole once-monthly 50 mg (21.80%, P ⩽0.001). Conclusions Aripiprazole once-monthly 400 mg was non-inferior to oral Aripiprazole, and the reduction in Kaplan-Meier estimated impending relapse rate at week 26 was statistically significant v. Aripiprazole once-monthly 50 mg. [1]: http://clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00706654&atom=%2Fbjprcpsych%2Fearly%2F2014%2F05%2F23%2Fbjp.bp.113.134213.atom

  • pharmacokinetics tolerability and safety of Aripiprazole once monthly in adult schizophrenia an open label parallel arm multiple dose study
    Schizophrenia Research, 2013
    Co-Authors: Suresh Mallikaarjun, Robert D Mcquade, William H. Carson, Raymond Sanchez, John M Kane, Patricia Bricmont, Robert A Forbes, Wolfgang W Fleischhacker
    Abstract:

    This 24-week, open-label, Phase Ib, parallel-arm, multiple-dose trial assessed the pharmacokinetics, safety and tolerability of a once-monthly injection of Aripiprazole (Aripiprazole once-monthly) in 41 subjects with schizophrenia. The objective was to determine if Aripiprazole plasma concentrations (at doses of 200, 300 and 400mg) were within the therapeutic range observed for the oral tablet (10-30 mg). Completion rates were 36.4% (n=4/11), 50.0% (n=8/16) and 71.4% (n=10/14) for the 200mg, 300 mg and 400mg groups, respectively. Patients were stabilized on oral Aripiprazole (10mg/day) before the first injection and received oral Aripiprazole (10mg/day) concomitantly with the first dose of Aripiprazole once-monthly for 14 days. Administration of Aripiprazole once-monthly at doses of 300 and 400mg provided sustained mean Aripiprazole plasma concentrations comparable with the concentration range observed following multiple consecutive daily doses of oral Aripiprazole. In contrast, plasma concentrations following administration of Aripiprazole once-monthly at a dose of 200mg were below the therapeutic range and pharmacokinetic parameters were not proportional to the administered dose compared with the 300 mg and 400mg doses. Treatment with Aripiprazole once-monthly, at any dose, did not result in any clinically meaningful changes from baseline in extrapyramidal symptom scales, clinical laboratory tests, vital signs, or electrocardiogram parameters. The most common treatment-emergent adverse events were vomiting (13.3%, 300 mg; 14.3%, 400mg), injection site pain (28.6%, 400mg), upper respiratory tract infection (10%, 200mg; 6.7% 300 mg; 14.3%, 400mg) and tremor (6.7%, 300 mg; 21.4%, 400mg). In conclusion, Aripiprazole once-monthly at doses of 300 and 400mg is a viable formulation for treatment of adults with schizophrenia.

  • Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia a 52 week multicenter randomized double blind placebo controlled study
    The Journal of Clinical Psychiatry, 2012
    Co-Authors: John M Kane, Robert D Mcquade, William H. Carson, Raymond Sanchez, Pamela Perry, Na Jin, B Johnson, Robert A Forbes, Wolfgang W Fleischhacker
    Abstract:

    OBJECTIVE: To evaluate the efficacy and tolerability of a once-monthly intramuscular (IM) depot formulation of the dopamine partial agonist Aripiprazole as maintenance treatment in adults meeting DSM-IV-TR schizophrenia criteria. METHOD: The study was conducted from July 2008 until February 2011. Subjects requiring chronic treatment with an antipsychotic entered a 4- to 12-week oral stabilization phase and received oral Aripiprazole (10-30 mg/d). Subjects meeting stability criteria for 4 weeks entered an IM-depot stabilization phase in which they received 400-mg Aripiprazole-IM-depot injections every 4 weeks (single decrease to 300 mg permitted) with coadministration of oral Aripiprazole tablets in the first 2 weeks. Subjects meeting stability criteria for 12 consecutive weeks were randomly assigned (2:1) to Aripiprazole-IM-depot or placebo during a 52-week, double-blind maintenance phase. The primary outcome measure was time to exacerbation of psychotic symptoms/impending relapse (event). Safety and tolerability were also assessed. RESULTS: 710 patients entered oral stabilization, 576 progressed to IM-depot stabilization, and 403 were randomly assigned to double-blind treatment. The study was terminated early because efficacy was demonstrated by the preplanned interim analysis (conducted after 64 events). Time to impending relapse was significantly delayed with Aripiprazole-IM-depot treatment compared with placebo in both the interim analysis and the final analysis (P < .0001, log-rank test). The hazard ratio (placebo/Aripiprazole-IM-depot) at final analysis was 5.03 (95% CI, 3.15-8.02). The rate of impending relapse was significantly lower with Aripiprazole-IM-depot than placebo at endpoint (final analysis, 10.0% [n = 27/269] vs 39.6% [n = 53/134]). Improvements in Clinical Global Impressions-Severity of Illness scale and Positive and Negative Syndrome Scale total scores were maintained with Aripiprazole-IM-depot treatment but showed significant worsening with placebo (change from double-blind baseline, P < .0001 for Aripiprazole-IM-depot vs placebo). The most common treatment-emergent adverse events (occurring in ≥ 5% of Aripiprazole-IM-depot subjects and greater than placebo) were insomnia, tremor, and headache. CONCLUSIONS: Aripiprazole-IM-depot significantly delayed time to impending relapse compared with placebo and appears to be a well-tolerated maintenance treatment option for schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00705783.

  • Aripiprazole monotherapy in the treatment of acute bipolar i mania a randomized double blind placebo and lithium controlled study
    Journal of Affective Disorders, 2009
    Co-Authors: Paul E. Keck, Robert D Mcquade, Raymond Sanchez, Paul J Orsulak, Andrew J Cutler, Anne Torbeyns, R Marcus, William H. Carson
    Abstract:

    Abstract Objectives To evaluate the efficacy and safety of Aripiprazole as acute and maintenance of effect monotherapy for acute bipolar mania. Methods Patients with acute bipolar I mania (DSM-IV-TR: YMRS ≥ 20), manic or mixed (with or without psychotic features) were randomized to double-blind Aripiprazole (15–30 mg/day; n = 155), placebo (n = 165) or lithium (900–1500 mg/day; n = 160) (1:1:1) for 3 weeks. Aripiprazole- and lithium-treated patients remained on blinded treatment for 9 additional weeks. The primary outcome was the mean change from baseline in YMRS Total score (LOCF) to Week 3. Secondary outcomes included the mean change from baseline in YMRS Total score (LOCF) at all other timepoints up to Week 12. Results Aripiprazole demonstrated significantly greater improvement than placebo in mean YMRS Total score from baseline to Day 2 (− 4.3 vs.− 2.8; p = 0.003), and up to Week 3 (− 12.6 vs. − 9.0; p  Conclusions Aripiprazole provided statistically significant improvement of acute mania within 2 days, continuing over 3 weeks and sustained over 12 weeks. The magnitude of improvement to Week 12 was similar with Aripiprazole and lithium.

  • Aripiprazole monotherapy in the treatment of acute bipolar i mania a randomized double blind placebo and lithium controlled study
    Journal of Affective Disorders, 2009
    Co-Authors: Paul E. Keck, Robert D Mcquade, Raymond Sanchez, Paul J Orsulak, Andrew J Cutler, Anne Torbeyns, R Marcus, William H. Carson
    Abstract:

    Abstract Objectives To evaluate the efficacy and safety of Aripiprazole as acute and maintenance of effect monotherapy for acute bipolar mania. Methods Patients with acute bipolar I mania (DSM-IV-TR: YMRS ≥ 20), manic or mixed (with or without psychotic features) were randomized to double-blind Aripiprazole (15–30 mg/day; n  = 155), placebo ( n  = 165) or lithium (900–1500 mg/day; n  = 160) (1:1:1) for 3 weeks. Aripiprazole- and lithium-treated patients remained on blinded treatment for 9 additional weeks. The primary outcome was the mean change from baseline in YMRS Total score (LOCF) to Week 3. Secondary outcomes included the mean change from baseline in YMRS Total score (LOCF) at all other timepoints up to Week 12. Results Aripiprazole demonstrated significantly greater improvement than placebo in mean YMRS Total score from baseline to Day 2 (− 4.3 vs.− 2.8; p  = 0.003), and up to Week 3 (− 12.6 vs. − 9.0; p p  = 0.005). Improvements in YMRS Total score were maintained to Week 12 for Aripiprazole (− 14.5) and lithium (− 12.7). Response rates at Week 3 were significantly higher with Aripiprazole (46.8%) and lithium (45.8%) than placebo (34.4%; both p Conclusions Aripiprazole provided statistically significant improvement of acute mania within 2 days, continuing over 3 weeks and sustained over 12 weeks. The magnitude of improvement to Week 12 was similar with Aripiprazole and lithium.

Paul E. Keck - One of the best experts on this subject based on the ideXlab platform.

  • Aripiprazole monotherapy in the treatment of acute bipolar i mania a randomized double blind placebo and lithium controlled study
    Journal of Affective Disorders, 2009
    Co-Authors: Paul E. Keck, Robert D Mcquade, Raymond Sanchez, Paul J Orsulak, Andrew J Cutler, Anne Torbeyns, R Marcus, William H. Carson
    Abstract:

    Abstract Objectives To evaluate the efficacy and safety of Aripiprazole as acute and maintenance of effect monotherapy for acute bipolar mania. Methods Patients with acute bipolar I mania (DSM-IV-TR: YMRS ≥ 20), manic or mixed (with or without psychotic features) were randomized to double-blind Aripiprazole (15–30 mg/day; n = 155), placebo (n = 165) or lithium (900–1500 mg/day; n = 160) (1:1:1) for 3 weeks. Aripiprazole- and lithium-treated patients remained on blinded treatment for 9 additional weeks. The primary outcome was the mean change from baseline in YMRS Total score (LOCF) to Week 3. Secondary outcomes included the mean change from baseline in YMRS Total score (LOCF) at all other timepoints up to Week 12. Results Aripiprazole demonstrated significantly greater improvement than placebo in mean YMRS Total score from baseline to Day 2 (− 4.3 vs.− 2.8; p = 0.003), and up to Week 3 (− 12.6 vs. − 9.0; p  Conclusions Aripiprazole provided statistically significant improvement of acute mania within 2 days, continuing over 3 weeks and sustained over 12 weeks. The magnitude of improvement to Week 12 was similar with Aripiprazole and lithium.

  • Aripiprazole monotherapy in the treatment of acute bipolar i mania a randomized double blind placebo and lithium controlled study
    Journal of Affective Disorders, 2009
    Co-Authors: Paul E. Keck, Robert D Mcquade, Raymond Sanchez, Paul J Orsulak, Andrew J Cutler, Anne Torbeyns, R Marcus, William H. Carson
    Abstract:

    Abstract Objectives To evaluate the efficacy and safety of Aripiprazole as acute and maintenance of effect monotherapy for acute bipolar mania. Methods Patients with acute bipolar I mania (DSM-IV-TR: YMRS ≥ 20), manic or mixed (with or without psychotic features) were randomized to double-blind Aripiprazole (15–30 mg/day; n  = 155), placebo ( n  = 165) or lithium (900–1500 mg/day; n  = 160) (1:1:1) for 3 weeks. Aripiprazole- and lithium-treated patients remained on blinded treatment for 9 additional weeks. The primary outcome was the mean change from baseline in YMRS Total score (LOCF) to Week 3. Secondary outcomes included the mean change from baseline in YMRS Total score (LOCF) at all other timepoints up to Week 12. Results Aripiprazole demonstrated significantly greater improvement than placebo in mean YMRS Total score from baseline to Day 2 (− 4.3 vs.− 2.8; p  = 0.003), and up to Week 3 (− 12.6 vs. − 9.0; p p  = 0.005). Improvements in YMRS Total score were maintained to Week 12 for Aripiprazole (− 14.5) and lithium (− 12.7). Response rates at Week 3 were significantly higher with Aripiprazole (46.8%) and lithium (45.8%) than placebo (34.4%; both p Conclusions Aripiprazole provided statistically significant improvement of acute mania within 2 days, continuing over 3 weeks and sustained over 12 weeks. The magnitude of improvement to Week 12 was similar with Aripiprazole and lithium.

  • Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, double-blind study versus placebo.
    The Journal of clinical psychiatry, 2007
    Co-Authors: Paul E. Keck, James M Eudicone, Robert D Mcquade, Ronald N Marcus, Joseph R. Calabrese, Roger S. Mcintyre, William H. Carson, Berit X. Carlson, Raymond Sanchez
    Abstract:

    Objective: A 26-week, double-blind, placebo-controlled relapse prevention study of Aripiprazole was designed a priori with a prospective, 74-week, double-blind, placebo-controlled extension phase. Efficacy and tolerability of Aripiprazole for relapse prevention in bipolar I disorder was, therefore, evaluated for 100 weeks. Method: Patients with DSM-IV bipolar I disorder, recent manic or mixed episode, received open-label Aripiprazole 15 or 30 mg/day (started at 30 mg/day) for 6 to 18 weeks. Patients achieving stabilization (Young Mania Rating Scale score ≤ 10 and Montgomery-Asberg Depression Rating Scale score ≤13 for 6 consecutive weeks) entered the double-blind phase, at which point they were randomly assigned to double-blind treatment with Aripiprazole or placebo for 26 weeks. The primary endpoint was time to relapse for any mood episode. Patients who completed the 26-week stabilization continued in a double-blind fashion with Aripiprazole or placebo for an additional 74 weeks and were monitored for relapse, efficacy, and tolerability. The study was conducted from March 2000 to June 2003. Results: In total, 161 patients met the stabilization criteria and were randomly assigned to Aripiprazole (N = 78) or placebo (N = 83). At 100 weeks, time to relapse was significantly longer with Aripiprazole (N = 7) than placebo (N = 5; hazard ratio = 0.53 [p =.011; 95% CI = 0.32 to 0.87]); however, a further 24 patients had discontinued due to study closure. Aripiprazole was superior to placebo in delaying time to manic relapse (p =.005; hazard ratio = 0.35 [95% CI = 0.16 to 0.75]); however, no significant differences were observed in time to depressive relapse (p =.602; hazard ratio = 0.81 [95% CI = 0.36 to 1.81]). The adverse events reported during 100 weeks of treatment with Aripiprazole versus placebo (≥ 5% incidence and twice placebo rate) were tremor, akathisia, dry mouth, hypertension, weight gain, vaginitis, abnormal thinking, pharyngitis, and flu syndrome. Mean weight change from baseline to 100 weeks (last observation carried forward) was +0.4 ± 0.8 kg with Aripiprazole and -1.9 ± 0.8 kg with placebo. Conclusions: Over a 100-week treatment period, Aripiprazole monotherapy was effective for relapse prevention in patients who were initially stabilized on Aripiprazole for 6 consecutive weeks, and it maintained a good safety and tolerability profile.

  • a randomized double blind placebo controlled 26 week trial of Aripiprazole in recently manic patients with bipolar i disorder
    The Journal of Clinical Psychiatry, 2006
    Co-Authors: Paul E. Keck, Linda Rollin, Robert D Mcquade, Ronald N Marcus, Joseph R. Calabrese, William H. Carson, Berit X. Carlson, Raymond Sanchez
    Abstract:

    Objective: To investigate the safety and efficacy of Aripiprazole in preventing relapse of a mood episode in recently manic- or mixed-episode patients with bipolar I disorder stabilized on Aripiprazole. Method: This randomized, double-blind, parallel-group, placebo-controlled, multicenter study enrolled patients from 76 centers in 3 countries (Argentina, Mexico, United States) from March 2000 to June 2003. Bipolar I disorder (DSM-IV) patients who had recently been hospitalized and treated for a manic or mixed episode entered an open-label stabilization phase (Aripiprazole monotherapy: 15 or 30 mg/day, 6-18 weeks). After meeting stabilization criteria (Young Mania Rating Scale score of ≤ 10 and Montgomery-Asberg Depression Rating Scale score of ≤ 13 for 6 consecutive weeks), 161 patients were randomly assigned to Aripiprazole or placebo for the 26-week, double-blind phase. The primary endpoint was time to relapse for a manic, mixed, or depressive episode (defined by discontinuation caused by lack of efficacy). Results: Aripiprazole was superior to placebo in delaying the time to relapse (p =.020). Aripiprazole-treated patients had significantly fewer relapses (25%) than placebo patients (43%; p =.013). Aripiprazole was superior to placebo in delaying the time to manic relapse (p =.01); however, no significant differences were observed in time to depressive relapse (p =.68). Weight gain (> 7% increase) occurred in 7 (13%) Aripiprazole-treated and 0 placebo-treated patients. Adverse events (> 5% incidence and twice that of placebo) reported by Aripiprazole-treated patients were akathisia, pain in the extremities, tremor, and vaginitis. Conclusions: Aripiprazole, 15 or 30 mg/day, was superior to placebo in maintaining efficacy in patients with bipolar I disorder with a recent manic or mixed episode who were stabilized and maintained on Aripiprazole treatment for 6 weeks, as shown by a longer time to relapse.

  • a placebo controlled double blind study of the efficacy and safety of Aripiprazole in patients with acute bipolar mania
    American Journal of Psychiatry, 2003
    Co-Authors: Paul E. Keck, Ronald N Marcus, Stavros Tourkodimitris, Mirza Ali, Amy Liebeskind, A Saha, Gary Ingenito
    Abstract:

    Objective: The authors compared the efficacy and safety of Aripiprazole, a novel antipsychotic, to placebo for treatment of patients in an acute manic or mixed episode of bipolar disorder. Method: This 3-week, multicenter, double-blind study randomly assigned 262 bipolar disorder patients in an acute manic or mixed episode to Aripiprazole, 30 mg/ day (reduced to 15 mg/day if needed for tolerability), or placebo. Patients remained hospitalized for at least 2 of the weeks. The primary efficacy measure was mean change from baseline in total score on the Young Mania Rating Scale; response was defined as a decrease in score of ≥50%. Results: Aripiprazole produced statistically significant mean improvements in total score on the Young Mania Rating Scale compared with placebo (–8.2 versus –3.4, respectively) and produced a significantly higher response rate (40% versus 19%). For key efficacy variables (response per Young Mania Rating Scale; Clinical Global Impression—Bipolar Version scores for severity of illness [mania] and change from preceding phase [mania]), Aripiprazole separated from placebo by day 4. The completion rate was significantly higher with Aripiprazole than with placebo (42% versus 21%). Discontinuations due to adverse events did not differ significantly between the Aripiprazole and placebo groups. There were no significant changes in body weight versus placebo, and Aripiprazole was not associated with elevated serum prolactin or QTc prolongation. Conclusions: Aripiprazole had significantly greater efficacy than placebo for the treatment of bipolar disorder patients in acute manic or mixed episodes and was safe and well tolerated in this randomized controlled trial.