Dataset Information

Lurasidone for the Treatment of Irritability Associated with Autistic Disorder.

ABSTRACT: The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to 6 weeks of double-blind treatment with lurasidone 20 mg/day (N = 50), 60 mg/day (N = 49), or placebo (N = 51). Efficacy measures included the Aberrant Behavior Checklist Irritability subscale (ABC-I, the primary endpoint) and the Clinical Global Impressions, Improvement (CGI-I) scale, and were analyzed using a likelihood-based mixed model for repeated measures. Least squares (LS) mean (standard error [SE]) improvement from baseline to Week 6 in the ABC-I was not significantly different for lurasidone 20 mg/day (-8.8 [1.5]) and lurasidone 60 mg/day (-9.4 [1.4]) versus placebo (-7.5 [1.5]; p = 0.55 and 0.36, respectively). CGI-I scores showed significantly greater LS mean [SE] improvement at Week 6 for lurasidone 20 mg/day versus placebo (2.8 [0.2] vs. 3.4 [0.2]; p = 0.035) but not for lurasidone 60 mg/day (3.1 [0.2]; p = 0.27). Discontinuation rates due to adverse events were: lurasidone 20 mg/day, 4.1%; 60 mg/day, 3.9%; and placebo, 8.2%. Adverse events with an incidence ?10% (lurasidone combined, placebo) included vomiting (18.0, 4.1%) and somnolence (12.0, 4.1%). Modest changes were observed in weight and selected metabolic parameters. In this study, once-daily, fixed doses of 20 and 60 mg/day of lurasidone were not demonstrated to be efficacious compared to placebo for the short-term treatment of children and adolescents with moderate-to-severe irritability associated with autistic disorder.

SUBMITTER: Loebel A

PROVIDER: S-EPMC4786592 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Lurasidone for the Treatment of Irritability Associated with Autistic Disorder.

Loebel Antony A Brams Matthew M Goldman Robert S RS Silva Robert R Hernandez David D Deng Ling L Mankoski Raymond R Findling Robert L RL

Journal of autism and developmental disorders 20160401 4

The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to 6 weeks of double-blind treatment with lurasidone 20 mg/day (N = 50), 60 mg/day (N = 49), or placebo (N = 51). Efficacy measures included the Aberrant B ...[more]

PMID: 26659550

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Project description:With increasing use of atypical antipsychotics among pediatric patients, detailed information about safety and tolerability is crucial. Data were pooled from two 8-week, randomized, double-blind, multicenter, parallel-group trials comparing aripiprazole versus placebo in subjects aged 6 to 17 years with irritability associated with DSM-IV-TR-diagnosed autistic disorder: one flexibly dosed (aripiprazole 2-15 mg/d; target of 5, 10, or 15 mg/d), the other fixed-dose (aripiprazole 5, 10, or 15 mg/d). The first was conducted from June 2006-April 2008, and the second, from June 2006-June 2008. Adverse events were characterized with respect to incidence, duration, severity, timing of peak incidence of onset, and dose-response relationship. Extrapyramidal symptoms, drooling, and metabolic parameters were evaluated. Three hundred thirteen subjects comprised the safety sample (aripiprazole 212, placebo 101). Discontinuations due to adverse events with aripiprazole versus placebo were, overall, 10.4% versus 6.9%; subjects 6-12 years: 10.8% versus 5.1%; and subjects 13-17 years: 8.9% versus 13.6%. Common adverse events with aripiprazole versus placebo included sedation (20.8% vs 4.0%), fatigue (16.5% vs 2.0%), vomiting (13.7% vs 6.9%), increased appetite (12.7% vs 6.9%), somnolence (10.4% vs 4.0%), and tremor (9.9% vs 0.0%). Most adverse events were mild or moderate and occurred early. Only fatigue showed a dose-response relationship (P < .05). Mean body weight change (last observation carried forward, 1.6 vs 0.4 kg) was higher with aripiprazole than placebo (P < .001). There were no between-treatment differences in metabolic changes. The extrapyramidal symptom-related adverse event incidence with aripiprazole versus placebo was, overall, 20.8% vs 9.9%; the incidence of akathisia-related events was 3.3% vs 8.9%. Aripiprazole was generally safe and well tolerated in subjects (6-17 years) with irritability associated with autistic disorder in these 8-week studies; clinicians should be aware of this clinical profile and strategies to manage adverse events if they occur. clinicaltrials.gov Identifiers NCT00332241 and NCT00337571.

Project description:BackgroundIrritability is a common and impairing occurrence in autistic youth, yet the underlying mechanisms are not well-known. In typically developing populations, differences in frustration response have been suggested as important driver of the behavioural symptoms of irritability. Research exploring the role of frustration response as a risk factor for irritability in autistic populations is limited and often uses parent report or observer ratings; objective measures of frustration response appropriate for use in autistic populations are required to advance the field.MethodsIn the current study, fifty-two autistic adolescents aged 13-17 years from a population-based longitudinal study completed an experimental task designed to induce frustration through exposure to periods of unexpected delay. Behavioural (number of button presses) and physiological (heart rate; HR) metrics were collected during delay periods. Irritability was measured using the parent-rated Affective Reactivity Index (ARI). Analyses used mixed-level models to test whether irritability was associated with different slopes of behavioural and physiological response to experimentally induced frustration during the task. Age and baseline HR (for the physiological data only) were included as covariates.ResultsAnalyses showed a marginal association between irritability and the slope of behavioural response (incident rate ratio (IRR) =.98, p=.06), and a significant association with the slope of physiological response (b=-.10, p=.04); higher levels of irritability were associated with a dampened behavioural and physiological response, as indicated by flatter slopes of change over the course of the task. The pattern of results largely remained in sensitivity analyses, although the association with physiological response became non-significant when adjusting for IQ, autism symptom severity, and medication use (b=-.10, p=.10).ConclusionsResults suggest that the current experimental task may be a useful objective measure of frustration response for use with autistic populations, and that a non-adaptive response to frustration may be one biological mechanism underpinning irritability in autistic youth. This may represent an important target for future intervention studies.

Project description:BackgroundBipolar 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.MethodsPatients 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.ResultsA 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).ConclusionsUp 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.

Dataset Information

Lurasidone for the Treatment of Irritability Associated with Autistic Disorder.

Publications

Lurasidone for the Treatment of Irritability Associated with Autistic Disorder.

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