The role of asenapine in the treatment of manic or mixed states associated with bipolar I disorder.
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SUBMITTER: Pompili M
PROVIDER: S-EPMC3101886 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
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The role of asenapine in the treatment of manic or mixed states associated with bipolar I disorder.
Pompili Maurizio M Venturini Paola P Innamorati Marco M Serafini Gianluca G Telesforo Ludovica L Lester David D Tatarelli Roberto R Girardi Paolo P
Neuropsychiatric disease and treatment 20110506
<h4>Background</h4>Bipolar disorders (BD) are of particular public health significance as they are prevalent, severe and disabling, and often associated with elevated risks of premature mortality. The aim of this concise overview is to investigate the role of asenapine in the treatment of manic and mixed states associated with BD type 1 disorder.<h4>Method</h4>MedLine, Excerpta Medica and PsycINFO searches were performed to identify papers in English published over the past 7 years. Search terms ...[more]
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Project description:Background:Bipolar disorder is associated with an increased risk of aggression. However, effective management of hostility and/or agitation symptoms may prevent patients from becoming violent. This analysis investigated the efficacy of the antipsychotic asenapine on hostility and agitation in patients with bipolar I disorder. Methods:Data were pooled from three randomized, double-blind, placebo-controlled, Phase III trials of asenapine in adults with manic or mixed episodes of bipolar I disorder (NCT00159744, NCT00159796, and NCT00764478). Post hoc analyses assessed the changes from baseline to day 21 on the Young Mania Rating Scale (YMRS) and the Positive and Negative Syndrome Scale (PANSS) hostility-related item scores in asenapine- or placebo-treated patients with at least minimal or mild symptom severity and on the PANSS-excited component (PANSS-EC) total score in agitated patients. Changes were adjusted for improvements in overall mania symptoms to investigate direct effects on hostility. Results:Significantly greater changes in favor of asenapine versus placebo were observed in YMRS hostility-related item scores (irritability: least squares mean difference [95% confidence interval] =-0.5 [-0.87, -0.22], P=0.001; disruptive-aggressive behavior: -0.7 [-0.99, -0.37], P<0.0001), PANSS hostility item score (-0.2 [-0.44, -0.04]; P=0.0181), and PANSS-EC total score (-1.4 [-2.4, -0.4]; P=0.0055). Changes in the YMRS disruptive-aggressive behavior score and the sum of the hostility-related items remained significant after adjusting for improvements in other YMRS item scores. Conclusion:Asenapine significantly reduced hostility and agitation in patients with bipolar I disorder; improvement was at least partially independent of overall improvement on mania symptoms.
| S-EPMC5729826 | biostudies-literature
Project description:Background:Patient characteristics and disease progression may affect response to pharmacologic intervention in bipolar I disorder. Asenapine is approved for acute treatment of manic/mixed episodes of bipolar I disorder in patients 10-17 years old. Post hoc analyses assessed asenapine efficacy in pediatric patients by current manic or mixed episode, number of lifetime episodes, and baseline body mass index (BMI). Patients and methods:Data were obtained from a 3-week, randomized, double-blind, placebo-controlled, parallel-group trial of asenapine 2.5, 5.0, or 10.0 mg twice daily (BID) in male or female patients (10-17 years) with bipolar I disorder (NCT01244815). Patients were stratified by current episode type (Diagnostic and Statistical Manual of Mental Disorders, fourth edition - defined mixed/manic), number of lifetime episodes (<3, 3-5, >5), and baseline BMI tertile. Changes from baseline to day 21 in Young Mania Rating Scale (YMRS) total score and Clinical Global Impressions Scale for use in Bipolar Illness (CGI-BP) were assessed in asenapine subgroups vs placebo. Results:In patients with mixed episodes, differences in YMRS and CGI-BP scores were statistically significant for each asenapine dose vs placebo (P<0.001) at day 21; in patients with manic episodes, significant differences vs placebo were seen in all groups (P<0.05) except 2.5 mg BID on the YMRS. In patients with <3 previous mixed/manic episodes, significant differences in YMRS and CGI-BP scores were observed for all asenapine doses vs placebo (P<0.05). In patients with 3-5 or >5 previous episodes, asenapine 10 mg BID was significantly different than placebo (P<0.05) on both scales; differences vs placebo varied for lower doses. Baseline body weight or BMI did not appear to influence the efficacy of asenapine. Conclusion:Asenapine was effective in the treatment of pediatric patients with bipolar I disorder. Efficacy did not appear to be influenced by the type of current episode, stage of disease progression, or baseline body weight/BMI.
| S-EPMC6080865 | biostudies-literature
Project description:Asenapine (Saphris(®)) is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD). Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be similarly modest. Asenapine does not appear to cause any clinically significant QTc prolongation. The most commonly reported extra-pyramidal symptom associated with asenapine was akathisia. Overall, asenapine appears to be a relatively well-tolerated atypical antipsychotic, effective in the treatment of acute manic and mixed episodes of BD.
| S-EPMC4675633 | biostudies-literature
Project description:Many bipolar disorder patients exhibit mixed affective states, which portend a generally more severe illness course and treatment resistance. In the previous renditions of Diagnostic and Statistical Manual mixed states were narrowly defined in the context of bipolar I disorder, but with the advent of DSM-5 the term "mixed episode" was dropped and replaced by "mixed features" specifier which could be broadly applied to manic, hypomanic and depressive episodes in both the bipolar spectrum and major depressive disorders. This paradigm shift reflected their significance in the prognosis and overall management of mood disorders, so that the clinicians should thoroughly familiarize themselves with the contemporary notions surrounding these conditions. The purpose of this manuscript is to bring to light the current conceptualizations regarding the etiology, pathogenesis and treatment of mixed states. To achieve this goal, in June 2016 an extensive literature search was undertaken using the PubMed database. Some exploratory terms utilized included "mixed states", "mixed episodes", "switching", "rapid cycling" cross referenced with "bipolar disorder". Focusing on the most relevant and up to date studies, it was revealed that mixed states result from genetic susceptibility in the circadian and dopamine neurotransmission apparatuses and disturbance in the intricate catecholamine-acetylcholine neurotransmission balance which leads to mood fluctuations. The management of mixed states is challenging with atypical antipsychotics, newer anticonvulsants and electroconvulsive therapy emerging as the foremost treatment options. In conclusion, while progress has been made in the neurobiological understanding of mixed states, the currently available therapeutic modalities have only shown limited effectiveness.
| S-EPMC5299125 | biostudies-literature
Project description:BackgroundBipolar disorder (BPD) is prevalent and is associated with a significant economic burden. Asenapine, the first tetracyclic antipsychotic approved in Canada for the treatment of BPD, has shown a comparable efficacy profile to other atypical antipsychotics. In addition, it is associated with a favourable metabolic profile and minimal weight gain potential. This study aimed to assess the economic impact of asenapine compared to olanzapine in the treatment of BPD in Canada.MethodsA decision tree combined with a Markov model was constructed to assess the cost-utility of asenapine compared with olanzapine. The decision tree takes into account the occurrence of extrapyramidal symptoms (EPS), the probability of switching to a different antipsychotic, and the probability of gaining weight. The Markov model takes into account long-term metabolic complications including diabetes, hypertension, coronary heart diseases (CHDs), and stroke. Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective over a five-year time horizon with yearly cycles.ResultsIn the treatment of BPD, asenapine is a dominant strategy over olanzapine from both a MoH and a societal perspective. In fact, asenapine is associated with lower costs and more quality-adjusted life years (QALYs). Results of the probabilistic sensitivity analysis indicated that asenapine remains a dominant strategy in 99.2% of the simulations, in both a MoH and a societal perspective, and this result is robust to the many deterministic sensitivity analyses performed.ConclusionsThis economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine in the treatment of BPD in Canada.
| S-EPMC3905654 | biostudies-literature
Project description:Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms.In the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796]), 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter), placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1) Montgomery-Asberg Depression Rating Scale (MADRS) total score ?20 (n = 132); (2) Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D) scale severity score ?4 (n = 170); (3) diagnosis of mixed episodes (n = 302) by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures.Decreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3.These post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in patients with acute bipolar depression are necessary to confirm the generalizability of these findings.
| S-EPMC3152513 | biostudies-literature
Project description:Published studies in adult and pediatric bipolar disorder have used different definitions of treatment response. This analysis aimed to compare different definitions of response in a large sample of children and adolescents.Anexploratory analysis of a 4-week, multicenter, placebo-controlled study assessed patients (n=296; ages, 10-17 years) with an acute manic/mixed episode associated with BIPOLAR I disorder who were randomized to aripiprazole (10 or 30?mg/day) or placebo. The primary efficacy endpoint was mean change from baseline to week 4 in young mania rating scale (YMRS) total score. Additional assessments included: clinical global impressions-bipolar disorder (CGI-BP) Overall and mania scales, child global assessment scale (CGAS), and parent and subject general behavior inventory. Response was compared across seven operational definitions. Cohen's ? and Spearman's correlation tested relationships between various response definitions or changes in outcome measures and clinically meaningful improvement (defined as a CGI-BP overall improvement score of 1 or 2).Response rates varied depending upon the operational definition, but were highest for 95% reliable change (statistical method used to determine individual change from previous assessment) and ?33% reduction in YMRS total score. Response rate definitions with the highest validity in terms of predicting clinically meaningful improvement were: ?50% reduction on YMRS (?=0.64), a composite definition of response (YMRS <12.5, children's depression rating scale-revised (CDRS-R) ?40, and CGAS ?51; ?=0.59), and 95% reliable change on the CGAS or 33% reduction on YMRS (?=0.56). Parent ratings of symptoms were generally better at detecting symptom improvement than were subject ratings (?=?0.4-0.5 vs. ?0.2 when compared with CGI-BP overall improvement score).Clinically meaningful definitions of response in acute treatment of a manic/mixed episode in pediatric subjects include a 50% change in YMRS and a composite measure of response. Parent-reported measures of symptom improvement appear reliable for assessing symptom change.
| S-EPMC3696952 | biostudies-literature
Project description:IntroductionBipolar disorder is a chronic disease characterized by periods of mania or hypomania, depression, or a combination of both (mixed state). Because bipolar disorder is one of the leading causes of disability, it represents an important economic burden on society. Asenapine (ASE) is a new second-generation antipsychotic developed and approved for the treatment of manic or mixed episodes associated with bipolar disorder. The objective of the present study was to assess the cost-effectiveness of ASE compared to olanzapine (OLA) in the treatment of patients experiencing mixed episodes associated with bipolar I disorder in the context of the Italian National Health Service (NHS).MethodsA pharmacoeconomic model was developed to simulate the management of Italian bipolar I patients with mixed episodes over a 5-year time horizon by combining clinical parameters with resource utilization. An expert panel of Italian psychiatrists and health economists was responsible for adapting a UK model to the Italian context. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio, where effectiveness is measured in terms of quality adjusted life-years gained. Scenario analyses, sensitivity analyses, and a probabilistic sensitivity analysis were performed to test the robustness of the model.ResultsThis pharmacoeconomic model showed that ASE resulted to be dominant over OLA; in fact, ASE was associated with lower direct costs (derived largely by the savings from hospitalizations avoided) and also generated a better quality of life. Results were robust to changes in key parameters; both scenario analyses and sensitivity analyses demonstrated model reliability.ConclusionsResults from this study suggest that the management of bipolar I patients with mixed episodes using ASE as alternative to OLA can lead to cost saving for the Italian NHS and improve patients quality of life.
| S-EPMC4147242 | biostudies-literature
Project description:Asenapine, administered as a twice-daily (BID) sublingual tablet, is approved in the US as monotherapy for the acute treatment of manic and mixed episodes of bipolar I disorder in children and adolescents aged 10-17 years based on the positive results of one 3-week, double-blind, placebo-controlled study; the recommended dose is 2.5-10 mg BID. Although asenapine has been studied in pediatric patients with schizophrenia, it is not approved for this indication. Asenapine is not approved for pediatric use in bipolar I disorder or schizophrenia in other major markets. To inform clinicians treating psychiatric disorders in pediatric patients, we have summarized the neuropharmacology, pharmacokinetics, clinical trial experience, and clinical use of asenapine in pediatric patients. After rapid absorption through the oral mucosa, the pharmacokinetic profile of asenapine in pediatric patients is similar to that which is observed in adult patients, indicating that the recommended adult dosage does not need to be adjusted for pediatric use. Intake of food and water should be avoided for 10 min after administration. In clinical trials, asenapine was generally safe and well tolerated in pediatric patients with bipolar I disorder and schizophrenia. Serious adverse effects were generally related to worsening of the underlying psychiatric disorder. The most common treatment-emergent adverse events (TEAEs) in both indications were sedation and somnolence. Like some other second-generation antipsychotic agents, weight gain and changes in some metabolic parameters were noted; oral effects (e.g., oral hypoesthesia, dysgeusia, paresthesia) related to sublingual administration did not typically result in treatment discontinuation and were generally transient. Extrapyramidal symptom TEAEs occurred in ?5% of asenapine-treated patients in the acute and long-term studies in bipolar I disorder and schizophrenia.
| S-EPMC5856894 | biostudies-literature
Project description:Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.
| S-EPMC4671523 | biostudies-literature