Dataset Information

Asenapine Treatment in Pediatric Patients with Bipolar I Disorder or Schizophrenia: A Review.

ABSTRACT: 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.

SUBMITTER: Stepanova E

PROVIDER: S-EPMC5856894 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Asenapine Treatment in Pediatric Patients with Bipolar I Disorder or Schizophrenia: A Review.

Stepanova Ekaterina E Grant Bradley B Findling Robert L RL

Paediatric drugs 20180401 2

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 pediat ...[more]

PMID: 29170943

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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.

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.

Project description:Sublingually administered asenapine was approved in March 2015 by the United States Food and Drug Administration for patients aged 10-17 years with an acute manic or mixed episode associated with bipolar I disorder (BP-1). This is the first long-term safety and tolerability study of asenapine in this population.Following the 3-week randomized, double-blind, placebo-controlled trial of patients aged 10-17 years with an acute manic or mixed episode associated with BP-1, patients could enroll in this flexible-dose (2.5-10 mg twice daily) open-label extension (OLE) study for an additional 50 weeks, conducted from August 2011 to September 2014 in the United States and Russia. Treatment-emergent adverse events (TEAEs) were assessed and predefined TEAEs of interest reported in addition to metabolic and anthropometric parameters. The Young Mania Rating Scale (YMRS) and Clinical Global Impressions scale in bipolar illness (CGI-BP) were used to assess effectiveness.A total of 321 patients (lead-in study treatment: placebo, n = 80; asenapine, n = 241) were included; 267 (83.2 %) reported one or more TEAE and 181 (56.4 %) discontinued early, 48 (15.0 %) due to TEAEs. Of the predefined TEAEs of interest, combined somnolence/sedation/hypersomnia occurred most frequently (42.4 %) followed by oral hypoesthesia/dysgeusia (7.5 %). In total, 109 (34.8 %) patients experienced clinically significant weight gain (?7 % increase). No clinically meaningful changes were noted for laboratory parameters measured. Eighteen patients met the criteria for new-onset metabolic syndrome (MBS) post-baseline during the extension study, whereas 10 patients who met MBS criteria at baseline did not meet MBS criteria at endpoint. A total of 12 patients met MBS at baseline and endpoint. Mean change in YMRS total score from OLE baseline was -9.2 points at week 50, and change in CGI-BP severity overall score was similar among all treatment groups (those who initially received asenapine and those who initially received placebo). After 26 weeks of treatment in the OLE, 79.2 % of patients were classified as YMRS 50 % responders relative to acute trial baseline.Asenapine was generally well tolerated in pediatric patients with BP-1 during ?50 weeks of open-label treatment; among predefined TEAEs of interest, the combination of somnolence/sedation/hypersomnia was the most common. Trial registration ClinicalTrials.gov: NCT01349907.

Dataset Information

Asenapine Treatment in Pediatric Patients with Bipolar I Disorder or Schizophrenia: A Review.

Publications

Asenapine Treatment in Pediatric Patients with Bipolar I Disorder or Schizophrenia: A Review.

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