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51 ReferencesA randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder
Abstract
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.
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 < or = 10 and Montgomery-Asberg Depression Rating Scale score of < or = 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).
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 (> or = 7% increase) occurred in 7 (13%) aripiprazole-treated and 0 placebo-treated patients. Adverse events (> or = 5% incidence and twice that of placebo) reported by aripiprazole-treated patients were akathisia, pain in the extremities, tremor, and vaginitis.
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.
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- Like ziprasidone, aripiprazole is approved for the acute treatment of manic or mixed episodes associated with bipolar I disorder and for maintenance therapy (Abilify ® [aripiprazole] tablets, 2012; Geodon ® [ziprasidone HCl] capsules, 2012), but has two negative studies for bipolar depression (Thase et al., 2008). Also, although aripiprazole has a generally favorable metabolic profile (Kemp et al., 2010), it has been associated with considerable weight gain in some patients with bipolar disorder (Keck, Jr. et al., 2007; Keck, Jr. et al., 2006). Behavioral and lifestyle modification, which involve initiating a basic exercise routine and making dietary changes, are important components of treatment (McElroy and Keck, Jr., 2012; McIntyre et al., 2012).
[Show abstract] [Hide abstract] ABSTRACT: The most commonly used pharmacologic therapies for bipolar depression are mood stabilizers, atypical antipsychotics, and antidepressants. This paper reviews common side effects associated with these medications and provides recommendations for managing adverse medication effects in clinical practice. Narrative review based on literature searches of Medline and evidence-based treatment guidelines for agents that have been approved by the US Food and Drug Administration and/or are commonly used to treat bipolar depression. Side effects of bipolar depression pharmacotherapies are common and vary by medication, with weight gain, metabolic dysregulation, sedation/somnolence, and akathisia among those observed most frequently. These adverse events (weight gain and sedation/somnolence, in particular) negatively affect treatment adherence in patients with bipolar disorder. Furthermore, endocrine and metabolic comorbidities, weight gain, and obesity may reduce the likelihood of positive clinical responses to pharmacologic therapies. Clinicians may consider switching patients to bipolar depression medication(s) with a lower propensity for sedation or adverse metabolic effects. Lifestyle modification (e.g., dietary changes, exercise) is an important component in the treatment of weight gain/obesity, dyslipidemia, hypertension, and hyperglycemia; in addition, a wide range of medications are available as therapeutic options for patients in whom non-pharmacologic management strategies are insufficient. The use of adjunctive medication may also reduce treatment-related sedation and somnolence. The selection of relevant studies from the literature search relied primarily on the author's expertise in the area of bipolar depression and knowledge of the issues addressed. Successful treatment of bipolar depression extends beyond managing mood symptoms to also monitoring adverse medication events and managing associated medical disorders. Copyright © 2014 Elsevier B.V. All rights reserved.- In addition, as there is a greater likelihood that a subsequent episode is of the same polarity as the index episode, depressive relapses are much less likely during short observation periods and " time to episode " being the study endpoint (see section " What is the population under examination? "Calabrese et al. 2004)A post-hoc analysis of the 26-and 100-week monotherapy studies (Keck et al. 2006aKeck et al. , 2007) showed that time to any mood relapse in RC was significantly longer with aripiprazole monotherapy compared with placebo at week 26 ( P 0.033) andFor personal use only. studies.
[Show abstract] [Hide abstract] ABSTRACT: These guidelines are based on a first edition that was published in 2004, and have been edited and updated with the available scientific evidence up to October 2012. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the long-term treatment of bipolar disorder in adults. Methods . Material used for these guidelines are based on a systematic literature search using various data bases. Their scientific rigor was categorized into six levels of evidence (A – F) and different grades of recommendation to ensure practicability were assigned. Results . Maintenance trial designs are complex and changed fundamentally over time; thus, it is not possible to give an overall recommendation for long-term treatment. Different scenarios have to be examined separately: Prevention of mania, depression, or an episode of any polarity, both in acute responders and in patients treated de novo . Treatment might differ in Bipolar II patients or Rapid cyclers, as well as in special subpopulations. We identified several medications preventive against new manic episodes, whereas the current state of research into the prevention of new depressive episodes is less satisfactory. Lithium continues to be the substance with the broadest base of evidence across treatment scenarios. Conclusions. Although major advances have been made since the first edition of this guideline in 2004, there are still areas of uncertainty, especially the prevention of depressive episodes and optimal long-term treatment of Bipolar II patients.- In addition, few patients required a dose reduction; the majority of patients (92.6%) received aripiprazole 24 mg/day despite the option for dose reduction . Importantly, the AE profi le seen in Asian patients was similar to that seen in previous short- (Keck et al. 2003; Sachs et al. 2006) and long-term studies (Keck et al. 2006Keck et al. , 2007) conducted in Western populations.
[Show abstract] [Hide abstract] ABSTRACT: Objective. To investigate the efficacy and safety of aripiprazole in Asian patients with manic or mixed episodes associated with bipolar I disorder. Methods. Subjects were randomised to aripiprazole (24 mg/day; reduced to 12 mg/day if needed for tolerability; n = 128) or placebo (n = 130) for 3 weeks in this multicentre, double-blind study. The primary efficacy measure was mean change from baseline in Young Mania Rating Scale (YMRS) Total score. Results. A total of 136 patients (aripiprazole 56.3%; placebo 49.2%) completed the study. The majority of patients (92.6%) received aripiprazole 24 mg/day. Aripiprazole produced statistically significant mean improvements in YMRS Total scores compared with placebo from Day 4 through to Week 3 (-11.3 vs. -5.3; P < 0.001). The most common adverse events (> 15% of patients; aripiprazole vs. placebo) were akathisia (22.0 vs. 5.6%) and insomnia (16.3 vs. 9.6%). Aripiprazole treatment resulted in no significant difference from placebo in change in mean body weight from baseline (-0.4 vs. -0.7 kg; P = 0.231). Aripiprazole was not associated with an elevated serum prolactin level. Conclusions. Aripiprazole had significantly greater efficacy than placebo for the treatment of acute manic or mixed episodes associated with bipolar I disorder in Asian patients. Treatment was generally safe and well tolerated.- The dose range is from 5 to 20mgs/day. Aripiprazole is effective in preventing manic relapses as monotherapy (Keck et al. 2006) and the response rate is nearly 60% when it is continued for 100 weeks (Keck et al. 2007). The dose range is from 15 to 30mgs/day.
- L'aripiprazole par contre a montré une efficacité dans la prévention des rechutes maniaques mais pas dans celle des rechutes dépressives [16] [15].
[Show abstract] [Hide abstract] ABSTRACT: Bipolar depression, the most common phase of bipolar disorder, causes significant morbidity and mortality. Lithium, anticonvulsants or antidepressants offer some clinical efficacy. However, efficacy can be limited and side effects are sometimes problematic. There is still a major unmet need for effective, well-tolerated agents for the treatment of bipolar depression. The second-generation antipsychotics, with their proven efficacy against manic symptoms, are emerging as candidates for use against the depressive phase of bipolar disorder. Several studies have shown that some second-generation antipsychotics may improve depressive symptoms in mixed episodes in patients with bipolar disorder. More recently, specific studies have been performed in patients with bipolar depressive episodes. Quetiapine or olanzapine, as monotherapy or associated with other compounds, demonstrate an interesting efficacy. The international guidelines for the treatment of bipolar depression have identified quetiapine as a first line treatment in monotherapy. Second generation antipsychotics may prove to be important future treatments for patients with bipolar depression. Copyright © 2011 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.- Aripiprazole acts as a partial agonist at the pre-synaptic dopamine autoreceptors and post-synaptic D2 receptors (where it may have a higher intrinsic activity).8,9 This in vitro profile provides for functional antagonism in hyperdopaminergic states and functional agonism in hypodopaminergic states.10 Dehydroaripiprazole, has similar pharmacodynamic effects at the D2 receptors.7
[Show abstract] [Hide abstract] ABSTRACT: We aimed to review and synthesize results reporting on the maintenance efficacy of Aripiprazole in adults with bipolar I disorder. Aripiprazole is FDA approved for the acute and maintenance treatment of bipolar I disorder. Aripiprazole's efficacy during the long-term treatment of bipolar disorder is supported by extension of acute phase studies and long-term (ie, 100-week) double-blind placebo controlled recurrence prevention registration trials. Aripiprazole is not established as efficacious in the acute or maintenance treatment of bipolar depression. Moreover, aripiprazole's efficacy during the acute or maintenance phase of bipolar II disorder has not been sufficiently studied. Aripiprazole has a relatively lower hazard for metabolic disruption and change in body composition when compared to other atypical agents (eg, olanzapine, quetiapine). Moreover, aripiprazole has minimal propensity for sedation, somnolence and prolactin elevation. Aripiprazole is associated with extrapyramidal side effects, notably akathisia, which in most cases is not severe or treatment limiting. Future research vistas are to explore aripiprazole's efficacy in bipolar subgroups; recurrence prevention of bipolar depression; and in combination with other mood stabilizing agents.
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