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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    ABSTRACT: The issue of mixed states has an important place in the debate on psychiatric nosography since the end of XIXth century. The current definition of mixed states according to the DSM- IV, as a thymic episode of bipolar disorder type I, is probably somewhat too restrictive in clinical practice. Due to the clinical heterogeneity of bipolar disorder, the mixed states will define within a dimensional approach, likely in the next DSM- V. As the evolution, the prognosis or the therapeutic strategies differ from what is applied in other thymic episodes, this transition from «mixed state» to manic or depressive episodes “with mixed features” may be relevant in practice.
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    ABSTRACT: Objectives. We reviewed the treatment of bipolar mixed states using efficacy data of licensed and non-licensed physical or pharmacological treatments. Methods. We conducted a literature search to identify published studies reporting data on mixed states. Grading was done using an in-house level of evidence and we compared the efficacy with treatment recommendations of mixed states in current bipolar disorder guidelines. Results. A total of 133 studies reported data on mixed states, and seven guidelines differentiate the acute treatment of mixed states from pure states. The strongest evidence in treating co-occurring manic and depressive symptoms was for monotherapy with aripiprazole, asenapine, extended release carbamazepine, valproate, olanzapine, and ziprasidone. Aripiprazole was recommended in three guidelines, asenapine in one, and carbamazepine and ziprasidone in two. As adjunctive treatment, the strongest evidence of efficacy was for olanzapine plus lithium or valproate. For maintenance, there is evidence for the efficacy of monotherapy with valproate, olanzapine, and quetiapine. In the six guidelines valproate or olanzapine are first line monotherapy options; one recommends quetiapine. Recommended add-on treatments are lithium or valproate plus quetiapine. Conclusions. There is a lack of studies designed to address the efficacy of medications in mixed affective symptoms. Guidelines do not fully reflect the current evidences.
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