Role of sublingual asenapine in treatment of schizophrenia.
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ABSTRACT:
SUBMITTER: Citrome L
PROVIDER: S-EPMC3104691 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
Publications
Role of sublingual asenapine in treatment of schizophrenia.
Neuropsychiatric disease and treatment 20110526
Asenapine tablets are a new option for the treatment of schizophrenia. Sublingual administration is essential because bioavailability if ingested is less than 2%. Efficacy is supported by acute and long-term randomized controlled studies conducted by the manufacturer, with asenapine 5 mg twice daily evidencing superiority over placebo in six-week studies of acute schizophrenia, and flexibly-dosed asenapine (modal dose 10 mg twice daily) superior to placebo in a 26-week maintenance of response st ...[more]
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Project description:BackgroundSchizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia.ObjectivesTo determine the clinical effects of asenapine for adults with schizophrenia or other schizophrenia-like disorders by comparing it with placebo.Search methodsWe searched the Cochrane Schizophrenia Group's Trials Register (July 04, 2014) which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitation for inclusion of records into the register. We inspected references of all included studies for further relevant studies.Selection criteriaOur review includes randomised controlled trials (RCTs) comparing asenapine with placebo in adults (however defined) with schizophrenia or related disorders, including schizophreniform disorder, schizoaffective disorder and delusional disorder, again, by any means of diagnosis.Data collection and analysisWe inspected citations from the searches and identified relevant abstracts, and extracted data from all included studies. For binary data we calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous data we calculated mean differences (MD). We used the GRADE approach to produce a 'Summary of findings' table which included our outcomes of interest, where possible. We used a fixed-effect model for our analyses.Main resultsWe obtained and scrutinised 41 potentially relevant records, and from these we could include only six trials (n = 1835). Five of the six trials had high risk of attrition bias and all trials were sponsored by pharmaceutical companies. Results showed a clinically important change in global state (1 RCT, n = 336, RR 0.81, 95% CI 0.68 to 0.97, low-quality evidence) and mental state (1 RCT, n = 336, RR 0.72, 95% CI 0.59 to 0.86, very low-quality evidence) at short-term amongst people receiving asenapine. People receiving asenapine demonstrated significant reductions in negative symptoms (1 RCT, n = 336, MD -1.10, 95% CI -2.29 to 0.09, very low-quality evidence) at short-term. Individuals receiving asenapine demonstrated significantly fewer incidents of serious adverse effects (1 RCT, n = 386, RR 0.29, 95% CI 0.14 to 0.63, very low-quality evidence) at medium-term. There was no clear difference in people discontinuing the study for any reason between asenapine and placebo at short-term (5 RCTs, n = 1046, RR 0.91, 95% CI 0.80 to 1.04, very low-quality evidence). No trial reported data for extrapyramidal symptoms or costs.Authors' conclusionsThere is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst minimising the risk of adverse effects. However due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. We identify a need for large-scale, longer-term, better-designed and conducted randomised controlled trials investigating the clinical effects and safety of asenapine.
| S-EPMC6464872 | biostudies-literature
Project description:After completion of a 6-week double-blind trial of asenapine sublingual tablets (10 or 20 mg/day) versus placebo in Asian patients with acute exacerbation of schizophrenia, including Japanese patients, this open-label study evaluated the safety and efficacy of a 52-week treatment with asenapine at flexible doses. In 201 subjects, including 44 who had received placebo (P/A group) and 157 who had received asenapine (A/A group) in the feeder trial, adverse events occurred at rates of 90.9% and 85.4% and serious adverse events at rates of 11.4% and 20.4%, respectively. One patient in the P/A group died. No clinically significant abnormal measurements of body weight, body mass index, or glycated hemoglobin, fasting plasma glucose, insulin, and prolactin levels were observed. The sustained efficacy rate, as evaluated by the Positive and Negative Syndrome Scale total score and other measures, remained at approximately 50% between 6 and 12 months of treatment. These results suggest that long-term treatment with asenapine is well tolerated and provides sustained efficacy.
| S-EPMC10496045 | 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:ObjectivesAsenapine, a potent serotonin 7 (5-HT7) receptor antagonist, was examined for efficacy as an antidepressant in depressed bipolar subjects. It was predicted that subjects with the genetic variant of the short form of the serotonin transporter (5HTTR) would be more likely to respond.Experimental designA subset of patients participating in a randomized, placebo-controlled study of the efficacy of asenapine in bipolar I depression also underwent genetic testing for the 5HTTR. Montgomery Åsberg Depression Rating Scale (MADRS) score was ? 26 prior to randomization to asenapine or placebo for 8 weeks. Gene testing was performed before breaking the blind.Principal observationsNine patients completing the study also underwent gene testing. At study end, the average MADRS improvement was -19.80 ± SD 8.59 for the 4 people randomized to asenapine and -3.80 ± 9.01 for the 5 people receiving placebo (P = 0.021, t = 2.88). Anxiety, as measured by the Hamilton Anxiety Rating Scale (HAM-A), also improved in asenapine-treated patients (-15.40 ± 6.15 vs. -2.80 ± 7.95, P = 0.023, t = 2.803). Six participants had the short form of the 5HTTR, and it is believed they influenced the significant outcome in this small sample.ConclusionsWhile this is a very small sample, asenapine appears to have a beneficial effect on both depression and anxiety in depressed bipolar I patients compared to treatment with placebo. Due to the large fraction of subjects with the short form, the hypothesis that the SF-5HTTR might increase asenapine response could not be adequately tested.
| S-EPMC7093720 | biostudies-literature
Project description:BackgroundBipolar 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.MethodMedLine, Excerpta Medica and PsycINFO searches were performed to identify papers in English published over the past 7 years. Search terms were "asenapine", "manic" OR "mixed states", "bipolar I disorder". Subjects included in this study suffered from BD type 1 disorder.ResultsTo date, only four studies of asenapine for the treatment of manic or mixed episodes associated with BD type 1 have been published.ConclusionResearch indicates that asenapine is generally well-tolerated, and that asenapine is efficacious and not inferior to olanzapine in the treatment of mixed or manic episodes associated with BD type 1 in the short-term and long-term.
| S-EPMC3101886 | biostudies-literature
Project description:About one third of patients with schizophrenia respond unsatisfactorily to antipsychotic treatment and are termed "treatment-resistant". Clozapine is still the gold standard in these cases. However, 40%-70% of patients do not improve sufficiently on clozapine either. In the search for more efficacious strategies for treatment-resistant schizophrenia, drugs with different pharmacological profiles seem to raise new hopes, but are they valid? The aim of this review was to evaluate the evidence for aripiprazole as a potential strategy in monotherapy or combination therapy for patients with treatment-resistant schizophrenia. The evidence for aripiprazole monotherapy and for the combination of aripiprazole with psychotropics other than clozapine is scant, and no recommendation can be made on the basis of the currently available data. More effort has been made in describing combinations of aripiprazole and clozapine. Most of the open-label and case studies as well as case reports have shown positive effects of this combination on overall psychopathology and to some extent on negative symptoms. Several reports describe the possibility of dose reduction for clozapine in combination with aripiprazole, a strategy that might help so-called "treatment-intolerant" patients. The findings of four randomized controlled trials with respect to changes in psychopathology seem less conclusive. The most commonly found beneficial effects are better metabolic outcomes and indicators of the possibility of reducing the clozapine dose. However, other side effects, such as akathisia, are repeatedly reported. Further, none of the studies report longer-term outcomes. In the absence of alternatives, polypharmacy is a common strategy in clinical practice. Combining aripiprazole with clozapine in clozapine-resistant or clozapine-intolerant patients seems to be worthy of further investigation from the pharmacological and clinical points of view.
| S-EPMC3373202 | biostudies-other
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 (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:Background: Inflammation plays a major role in the onset and maintenance of schizophrenia. The objective of the present work was to synthetize in a narrative review the recent findings in the field of inflammation in schizophrenia and their application in daily practice. Method: This review was based on the most recent meta-analyses and randomized controlled trials. Results: The disturbed cytokines depend on the phase of the illness. A meta-analysis of cytokines in schizophrenia found higher levels of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood in both patients with first-episode schizophrenia and relapsed patients than in healthy controls. Exploring detailed data on immune-inflammatory disturbances in SZ reveals that IL-6 is one of the most consistently disturbed cytokines. Other cytokines, including IL1, TNF, and IFN, are also disturbed in schizophrenia. Choosing a broad spectrum anti-inflammatory agent that may inhibit subsequent pathways might be particularly useful for the treatment of inflammatory schizophrenia. Highly sensitive C-Reactive Protein is a useful screening marker for detecting inflammation in SZ subjects. Anti-inflammatory agents have shown effectiveness in recently published meta-analyses. Only one study found a significant difference between celecoxib and placebo, but two found a trend toward significance on illness severity and one on positive symptoms. In addition, other published and unpublished data were included in another meta-analysis that concluded the significant effect of add-on celecoxib in positive symptoms in first episode patients. There is a lack of data to determine if aspirin is truly effective in schizophrenia to date. Other anti-inflammatory agents have been explored, including hormonal therapies, antioxidants, omega 3 fatty acids, and minocycline, showing significant effects for reducing total, positive, and negative score symptoms and general functioning. However, each of these agents has multiple properties beyond inflammation and it remains unclear how these drugs improve schizophrenia. Conclusion: The next step is to tailor anti-inflammatory therapy in schizophrenia, with two main challenges: 1. To provide a more efficient anti-inflammatory therapeutic approach that targets specific pathways associated with the pathology of schizophrenia. 2. To develop a more personalized approach in targeting patients who have the best chance of successful treatment.
| S-EPMC7093323 | biostudies-literature
Project description:Schizophrenia is a devastating mental disorder resulting in marked morbidity and mortality despite the optimal use of all currently available interventions. For this reason, the release of lumateperone (CaptylaR), also known as ITI-007, an orally administered, atypical antipsychotic provided a welcome novel tool for clinicians to utilize precision medicine to tailor an optimal treatment plan to the specific needs of each person with schizophrenia. To generate a foundation for clinicians to assess the risks and benefits of lumateperone in relation to other interventions for schizophrenia, we conducted a search of items for 'ITI-007' and 'lumateperone' on PubMed, ScienceDirect, Web of Science, Google Scholar, and www.clinicaltrials.gov. We present a critical evaluation of the limited information about lumateperone for schizophrenia, its use approved by the US Food and Drug Administration. Lumateperone merits consideration for patients with treatment-resistant schizophrenia and for patients with schizophrenia who are vulnerable to developing metabolic dysfunction and movement disorders. On the other hand, lumateperone should not be used for (a) women who are pregnant or breastfeeding, children, adolescents, and elderly patients with dementia-related psychosis, (b) patients who are at risk for cerebrovascular diseases, (c) patients who use inducers and moderate or strong inhibitors of the cytochrome P450-3A4 (CYP3A4) isozyme, and (d) patients who use alcohol and other sedating agents. Clinical trials from multiple centers without financial conflicts of interest to market lumateperone are needed to directly compare and contrast lumateperone and other antipsychotic agents to generate trustworthy evidence to be assessed objectively by clinicians treating patients with schizophrenia. Future investigations will provide the foundations to identify the evidence for comprehensive evaluations of the role of lumateperone in the treatment of people with schizophrenia and other conditions.
| S-EPMC8326816 | biostudies-literature