Efficacy and safety of aripiprazole in subpopulations with acute manic or mixed episodes of bipolar I disorder

Bipolar Disorder Research Program, UT Southwestern Medical Center, Dallas, Texas 75390-9121, USA.
Journal of Affective Disorders (Impact Factor: 3.71). 05/2008; 107(1-3):145-54. DOI: 10.1016/j.jad.2007.08.015
Source: PubMed

ABSTRACT This analysis was designed to assess the efficacy and safety of aripiprazole compared with placebo in subpopulations of patients with acute manic or mixed episodes of bipolar I disorder.
Acutely manic patients experiencing DSM-IV manic/mixed episodes of bipolar I disorder were pooled from two randomized, three-week, flexible-dose, double-blind, placebo-controlled trials (N=516) and stratified by disease severity (Young Mania Rating Scale, YMRS), episode type, presence or absence of psychotic features, episode frequency, age, gender, and baseline severity of depressive symptoms. Safety and treatment-emergent adverse-event analyses were also performed.
Aripiprazole significantly reduced mean YMRS total scores at end point compared with placebo in patients with more severe or less severe illness, with mixed or manic episodes, with or without psychotic features, or with a history of rapid or non-rapid cycling (p<0.01 for each subpopulation); in men and women (p=0.001 for both); in patients in the 18-40 and 41-55 year age groups (p<or=0.001 for both); and in three subgroups stratified by baseline severity of depressive symptoms using the Montgomery-Asberg Depression Rating Scale (p<0.05). The treatment-emergent adverse events reported in >or=5% of patients aged 18-40 years receiving aripiprazole were similar to those reported for the overall population.
This post hoc analysis utilized pooled data from two short-term studies.
Efficacy of the second-generation antipsychotic aripiprazole was noted across a broad range of subpopulations often associated with treatment resistance in patients experiencing manic or mixed episodes of bipolar I disorder.

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Available from: James M Eudicone, Jun 02, 2015
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    • "Conversely, antidepressant treatment to treat only depressive symptoms can induce a manic switch (Baldessarini et al., 2012; Fornaro et al., 2012; Pacchiarotti et al., 2011a; Valenti et al., 2011). The drugs that showed positive effects in the subset of patients with mixed mania as defined in DSM-IV in placebocontrolled trials (asenapine, olanzapine, and valproate) (Azorin et al., 2013; Baker et al., 2003; Nivoli et al., 2012; Swann et al., 1997; Yatham et al., 2013), and to some extent those that showed separation from placebo in pooled analysis (aripiprazole and ziprasidone) (Stahl et al., 2010; Suppes et al., 2008), may be the best candidates for the treatment of the newly defined DSM-5 mixed states. Of note, there are very few data on the use of quetiapine in acute mixed states but positive adjunctive longterm data (Vieta et al., 2012), and ziprasidone (Patkar et al., 2012) has been tested in depressive mixed states (which did not exist in the DSM-IV). "
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    ABSTRACT: The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) nomenclature for the co-occurrence of manic and depressive symptoms (mixed states) has been revised in the new DSM-5 version to accommodate a mixed categorical-dimensional concept. The new classification will capture subthreshold non-overlapping symptoms of the opposite pole using a "with mixed features" specifier to be applied to manic episodes in bipolar disorder I (BD I), hypomanic, and major depressive episodes experienced in BD I, BD II, bipolar disorder not otherwise specified, and major depressive disorder. The revision will have a substantial impact in several fields: epidemiology, diagnosis, treatment, research, education, and regulations. The new concept is data-driven and overcomes the problems derived from the extremely narrow definition in the DSM-IV-TR. However, it is unclear how clinicians will deal with the possibility of diagnosing major depression with mixed features and how this may impact the bipolar-unipolar dichotomy and diagnostic reliability. Clinical trials may also need to address treatment effects according to the presence or absence of mixed features. The medications that are effective in treating mixed episodes per the DSM-IV-TR definition may also be effective in treating mixed features per the DSM-5, but new studies are needed to demonstrate it.
    Journal of Affective Disorders 04/2013; 148(1). DOI:10.1016/j.jad.2013.03.007 · 3.71 Impact Factor
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    • "The APA Practice Guidelines (2002) recommended a combination of an antipsychotic and a mood stabilizer, although only limited data have been published on this treatment strategy. Most reports of treatment efficacy for combination antipsychotic/mood stabilizer regimens in MS are post-hoc analyses of samples of convenience in short trials that included both manic and MS patients (Keck et al., 2003; Suppes et al., 2008). Some of these studies lacked sufficient numbers of patients for subanalyses of patients with MS, and have only reported the effect of this treatment for manic, but not depressive symptoms(McElroy et al., 1992; Cassidy and Carroll, 2001). "
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    International clinical psychopharmacology 12/2012; 28(2). DOI:10.1097/YIC.0b013e32835c7590 · 3.10 Impact Factor
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    • "Trial PANSS-total PANSS-positive PANSS-negative PANSS-cognitive PANSS-hostility N (efficacy sample) Aripiprazole CN138-009 - - - - - 125 CN138-074 61.8 ± 16.7 - - - - 136 CN138-135 62.0 ± 13.7 - - 15.2 ± 3.4 10.1 ± 3.4 154 CN138-162 54.8 ± 10.3 16.0 ± 3.9 9.6 ± 2.6 14.7 ± 3.9 9.7 ± 2.6 152 CN138-007 - - - - - 267 - CN138008 - - - - - 171 Pooled mean 59.5 16.0 9.6 14.9 9.9 1,005 Pooled SD 13.7 3.9 2.6 3.6 3.0 Placebo CN138-009 - - - - - 123 CN138-074 62.5 ± 16.5 - - - - 132 CN138-135 63.9 ± 13.1 - - 15.3 ± 3.6 10.4 ± 3.6 163 CN138-162 54.4 ± 10.3 16.4 ± 4.9 9.4 ± 2.5 14.9 ± 3.7 9.7 ± 2.5 152 CN138-007 - - - - - 134 - CN138008 Pooled mean 60.3 16.4 9.4 15.1 10.0 704 Pooled SD 13.4 4.9 2.5 3.6 3.1 Comparator CN138-009 CN138-074 CN138-135 63.2 ± 12.9 - - 15.6 ± 3.5 10.5 ± 3.5 155 CN138-162 54.1 ± 10.3 16.1 ± 3.9 9.5 ± 2.5 14.6 ± 3.9 9.4 ± 2.5 161 CN138-007 CN138008 - - - - - 158 Pooled mean 58.6 16.1 9.5 15.1 9.9 474 Pooled SD 11.6 3.9 2.5 3.7 3.0 Dash indicates missing data. a Calculated from Suppes et al. 2008 [21] "
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