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Long-term use of lurasidone in patients with bipolar disorder: safety and effectiveness over 2 years of treatment.

ABSTRACT: BACKGROUND:Bipolar disorder is a chronic illness with a 2-year recurrence rate of approximately 50% among individuals receiving treatment in the community. The aim of this 18-month, open-label, continuation study was to evaluate the long-term safety and effectiveness of lurasidone in patients who initially presented with a major depressive episode associated with bipolar disorder, and who had completed at least 6 months of initial treatment with lurasidone. METHODS:Patients with bipolar I depression were enrolled in one of three 6-week, double-blind, placebo-controlled trials (monotherapy with lurasidone, 1 study; adjunctive therapy with lurasidone; and lithium or valproate, 2 studies). Study completers were eligible for a 6-month, open-label extension study of lurasidone utilizing flexible daily doses of 20-120 mg; extension completers were then eligible for an additional 18 months of continuation treatment with flexible, once-daily doses of lurasidone in the range of 20-80 mg. Concomitant therapy with mood stabilizers was permitted throughout the open-label extension and continuation studies. RESULTS:A total of 1199 patients entered, and 941 (78.5%) completed initial, double-blind, acute treatment, of whom 817/941 (86.8%) entered, and 559 (68.4%) completed the 6-month extension study; 122/559 patients (21.8%) entered the 18-month continuation study, of whom 19.7% of discontinued, including 6.6% due to adverse events and 1.6% due to insufficient efficacy. The mean dose of lurasidone during the 18-month continuation study was 61.8 mg/day, and the modal dose was 60 mg/day. Mean change in weight, from acute baseline to 18-month continuation endpoint was +0.8 kg (completers, n = 55); median changes in cholesterol and triglycerides were -3.0 mg/dL and +26.0 mg/dL, respectively. Based on a Kaplan-Meier analysis, the probability of relapse during 18 months of continuation treatment with lurasidone was estimated to be 18.3% in the monotherapy group and 29.1% in the adjunctive therapy group. Improvement in global illness severity was also maintained during 18 months of continuation therapy (CGI-S at continuation baseline, 2.1; 18-month completers, 1.7; LOCF-endpoint, 1.9). CONCLUSIONS:Up to 2 years of treatment with lurasidone was safe and well tolerated in this bipolar disorder population presenting with an index episode of depression. Improvement in depressive symptoms was maintained in the majority of patients treated with lurasidone, with relatively low rates of relapse, and with minimal effects on weight and metabolic parameters.

SUBMITTER: Pikalov A

PROVIDER: S-EPMC5332323 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Long-term use of lurasidone in patients with bipolar disorder: safety and effectiveness over 2 years of treatment.

Pikalov Andrei A Tsai Joyce J Mao Yongcai Y Silva Robert R Cucchiaro Josephine J Loebel Antony A

International journal of bipolar disorders 20170302 1

<h4>Background</h4>Bipolar disorder is a chronic illness with a 2-year recurrence rate of approximately 50% among individuals receiving treatment in the community. The aim of this 18-month, open-label, continuation study was to evaluate the long-term safety and effectiveness of lurasidone in patients who initially presented with a major depressive episode associated with bipolar disorder, and who had completed at least 6 months of initial treatment with lurasidone.<h4>Methods</h4>Patients with b ...[more]

PMID: 28168632

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Project description:BackgroundThe current study evaluated the long-term (52 week) safety and impact on symptom measures of lurasidone (with or without lithium or valproate) for the treatment of bipolar I disorder in Japanese patients.MethodsBipolar patients for this open-label flexibly dosed lurasidone (20-120 mg/day) study were recruited from those with a recent/current depressive episode who completed an initial 6 week, double-blind, placebo-controlled, lurasidone study (depressed group), and those with a recent/current manic, hypomanic, or mixed episode (non-depressed group) who agreed to enroll directly into the long-term study. Measures of adverse events and safety included treatment-emergent adverse events, vital signs, body weight, ECG, laboratory tests, and measures of suicidality and extrapyramidal symptoms. Symptom measures included Montgomery Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS).ResultsThe most common adverse events associated with lurasidone were akathisia (30.7%), nasopharyngitis (26.6%), nausea (12.1%), and somnolence (12.1%). Minimal changes in lipids and measures of glycemic control occurred. Mean change in body weight was + 1.0 kg in the non-depressed group and - 0.8 kg in the depressed group. MADRS total scores declined by a mean (SD) of 2.0 (14.7) points from long-term baseline to endpoint in the depressed group who had received placebo in the prior 6 week trial. The depressed group that had received lurasidone during the prior 6 week study maintained their depressive symptom improvements. For the non-depressed group, YMRS total scores decreased over time.LimitationsNo control group was included, treatment was open-label, and 49.7% of patients completed the 52 week study.ConclusionsLong-term treatment with lurasidone 20-120 mg/day for Japanese patients with bipolar disorder maintained improvements in depressive symptoms for depressed patients who were treated in a prior 6 week trial and led to improvements in manic symptoms among a newly recruited subgroup of patients with a recent/current manic, hypomanic, or mixed episode. Few changes in weight or metabolic parameters were evident.Clinical trial registrationJapicCTI-132319, clinicaltrials.gov-NCT01986114.

Project description:ObjectiveThe purpose of this study was to evaluate the short- and long-term efficacy and safety of ziprasidone in children and adolescents with bipolar I disorder.MethodsSubjects 10-17 years of age with a manic or mixed episode associated with bipolar I disorder participated in a 4 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE). Subjects were randomized 2:1 to initially receive flexible-dose ziprasidone (40-160 mg/day, based on weight) or placebo. Primary outcome was the change in Young Mania Rating Scale (YMRS) scores from baseline. Safety assessments included weight and body mass index (BMI), adverse events (AEs), vital signs, laboratory measures, electrocardiograms, and movement disorder ratings.ResultsIn the RCT, 237 subjects were treated with ziprasidone (n=149; mean age, 13.6 years) or placebo (n=88; mean age, 13.7 years). The estimated least squares mean changes in YMRS total (intent-to-treat population) were -13.83 (ziprasidone) and -8.61 (placebo; p=0.0005) at RCT endpoint. The most common AEs in the ziprasidone group were sedation (32.9%), somnolence (24.8%), headache (22.1%), fatigue (15.4%), and nausea (14.1%). In the OLE, 162 subjects were enrolled, and the median duration of treatment was 98 days. The mean change in YMRS score from the end of the RCT to the end of the OLE (last observation carried forward) was -3.3 (95% confidence interval, -5.0 to -1.6). The most common AEs were sedation (26.5%), somnolence (23.5%), headache (22.2%), and insomnia (13.6%). For both the RCT and the OLE, no clinically significant mean changes in movement disorder scales, BMI z-scores, liver enzymes, or fasting lipids and glucose were observed. One subject on ziprasidone in the RCT and none during the OLE had Fridericia-corrected QT interval (QTcF) ≥ 460 ms.ConclusionThese results demonstrate that ziprasidone is efficacious for treating children and adolescents with bipolar disorder. Ziprasidone was generally well tolerated with a neutral metabolic profile.Clinical trials registryNCT00257166 and NCT00265330 at ClinicalTrials.gov.

Project description:BackgroundSublingually 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.MethodsFollowing 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.ResultsA 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.ConclusionsAsenapine 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

Long-term use of lurasidone in patients with bipolar disorder: safety and effectiveness over 2 years of treatment.

Publications

Long-term use of lurasidone in patients with bipolar disorder: safety and effectiveness over 2 years of treatment.

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