Dataset Information

Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia.

ABSTRACT: The aim of this analysis was to compare the effects of 2 atypical antipsychotic agents, lurasidone (80 mg/d or 160 mg/d) and quetiapine XR (600 mg/d), on daytime alertness, and to evaluate the effects of daytime sleepiness on treatment outcomes in patients with an acute exacerbation of schizophrenia.Patients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for schizophrenia were randomized to 6 weeks of double-blind treatment with fixed doses of lurasidone 80 mg/d (n = 125), lurasidone 160 mg/d (n = 121), quetiapine XR 600 mg/d (n = 119), or placebo (n = 121), all dosed once daily in the evening, with food. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS).Daytime sleepiness improved in the lurasidone and placebo-treated groups but worsened in the quetiapine XR treatment group when compared to placebo (p = 0.001) and to either dose of lurasidone (both p < 0.01). Sedation associated with quetiapine XR treatment mediated an improvement in agitation [assessed by the Positive and Negative Syndrome Scale-Excitement (PANSS-EC) subscale] and a worsening in functional capacity [assessed by the University of California-San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B) total score]; these mediating relationships were not observed for the lurasidone or placebo treatment groups.In this 6-week double-blind study, treatment with lurasidone 80 mg or 160 mg, administered once daily in the evening, was associated with a reduction in daytime sleepiness similar in magnitude to placebo, while quetiapine XR 600 mg/d was associated with a significant increase in daytime sleepiness, compared to both lurasidone dose groups and placebo. Daytime sleepiness was associated with improvement in agitation and worsening in functional capacity for quetiapine XR, but not lurasidone or placebo-treated patients.

SUBMITTER: Loebel AD

PROVIDER: S-EPMC3968912 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia.

Loebel Antony D AD Siu Cynthia O CO Cucchiaro Josephine B JB Pikalov Andrei A AA Harvey Philip D PD

CNS spectrums 20131213 2

<h4>Objective</h4>The aim of this analysis was to compare the effects of 2 atypical antipsychotic agents, lurasidone (80 mg/d or 160 mg/d) and quetiapine XR (600 mg/d), on daytime alertness, and to evaluate the effects of daytime sleepiness on treatment outcomes in patients with an acute exacerbation of schizophrenia.<h4>Methods</h4>Patients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for schizophrenia were randomized to 6 weeks ...[more]

PMID: 24330860

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Project description:Quetiapine extended release (XR) and lithium are treatments with proven efficacy in acute mania. This randomized study evaluated the efficacy and safety of lithium or placebo as add-on to quetiapine XR in adult patients with manic or mixed symptoms of bipolar I disorder. In this 6-week, double-blind study (Trial D144AC00003), adult patients with DSM-IV-TR-diagnosed bipolar I disorder (current episode manic or mixed), a Young Mania Rating Scale (YMRS) total score ≥20, and score ≥4 on two of four core YMRS items were administered quetiapine XR (400 to 800 mg/day) and randomly assigned to receive add-on lithium (600 to 1,800 mg/day) or placebo. The primary efficacy end point was change in the YMRS total score from baseline to day 43, analyzed using a mixed-model for repeated measures (MMRM) approach. Secondary efficacy and safety end points were also measured. Rating scales were administered by trained staff. Three hundred fifty-six patients treated with quetiapine XR were randomized to add-on lithium (n = 173) or placebo (n = 183). Two hundred ninety-one patients (81.7%) completed the study. At day 43, least squares mean change in YMRS total score was -22.8 for add-on lithium and -20.1 for add-on placebo, a statistically significant treatment group difference of -2.69 (p < 0.001). On secondary measures, add-on lithium was associated with significant improvements in response, remission, illness severity, and overall illness versus add-on placebo (p < 0.05). The number needed to treat was 9.1 for response and 7.9 for remission for add-on lithium compared with add-on placebo. Lithium in combination with quetiapine XR was generally well tolerated, with a similar profile to quetiapine XR in combination with placebo. The addition of lithium to quetiapine XR therapy was associated with significantly greater efficacy than placebo as add-on and was generally well tolerated in patients with acute bipolar I mania. This study was registered under Clinicaltrials.gov Identifier NCT00931723.

Project description:ObjectivesTo evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD).Patients and methodsThis was a 10-week (8-week active treatment/2-week post-treatment) randomized, double-blind, placebo- and active-controlled study (D1448C00004). Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery-Åsberg Depression Rating Scale [MADRS] total score) at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement) and remission (score ≤8); Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions - Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI) global; and Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form percentage maximum total scores. Tolerability was assessed throughout.ResultsA total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward) with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346]) versus placebo (-15.61). There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37). Mixed-model repeated-measures analysis of observed-case data suggested that the primary analysis may not be robust. Most commonly reported adverse events included dry mouth, somnolence, and dizziness for quetiapine XR, and headache and nausea for escitalopram.ConclusionIn this study, neither quetiapine XR (150/300 mg/day) nor escitalopram (10/20 mg/day) showed significant separation from placebo. Both compounds have been shown previously to be effective in the treatment of MDD; possible reasons for this failed study are discussed. Quetiapine XR was generally well tolerated, with a profile similar to that reported previously.

Project description:Abstract Background: Several atypical antipsychotics are approved to treat adolescent patients with schizophrenia. However, risk for antipsychotic-associated weight gain and metabolic dysfunction underscores the need to identify additional evidence-based treatments that are both efficacious and well tolerated in this vulnerable patient population. Lurasidone is an atypical antipsychotic agent that has demonstrated efficacy in the treatment of adults with schizophrenia in the dose range of 40–160?mg/d. The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and safety of lurasidone in adolescent patients with schizophrenia. Methods: Adolescent patients (13–17 years old) who met DSM-IV-TR criteria for schizophrenia were randomized to 6 weeks of double-blind treatment with fixed-dose lurasidone 40?mg/d, 80?mg/d, or placebo. An MMRM analysis was performed to assess change from baseline to Week 6 on the primary (PANSS total score) outcome measure. An ANCOVA using an LOCF approach was performed to assess change from baseline on secondary endpoints: Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) and Children’s Global Assessment Scale (CGAS). Safety and tolerability assessments included adverse event reporting, weight, and laboratory measures. Results: A total of 327 patients (mean age = 15.4 years old) were randomized to receive lurasidone 40?mg/d (N = 108), 80?mg/d (N = 106) or placebo (N = 113). Performance on the PANSS total score at Week 6 demonstrated a placebo-adjusted LS mean improvement of ?8.0 (P < .001) for the 40?mg/d group and ?7.7 (P < .001) for the 80?mg/d group. Placebo-adjusted LS mean improvement at Week 6 on the PQ-LES-Q was 5.3 (P = .001) and 5.8 (P < .001) for the 40?mg/d and 80?mg/d groups, respectively; and, on the CGAS was 4.6 (P = .002) and 4.9 (P < .001) for the 40?mg/d and 80?mg/d groups, respectively. Study discontinuation due to adverse events was 8.0% in the placebo group and 3.7% in lurasidone treated patients. The most common adverse events (?5% in either lurasidone group and at least twice the rate of placebo) were: nausea, somnolence, akathisia, vomiting, and sedation. LS mean change in weight at week 6 for the lurasidone 40?mg/d, 80?mg/d, and placebo groups was 0.17?kg, 0.49?kg, and 0.05?kg, respectively. Median change at Week 6 (LOCF) in total cholesterol was ?4.0?mg/dL, ?2.0?mg/dL, and ?7.0?mg/dL, respectively; in triglycerides was ?2.0?mg/dL, 7.0?mg/dL, and ?2.0?mg/dL, respectively; and in glucose was 0.0?mg/dL, 1.0?mg/dL, and 0.0?mg/dL, respectively. Conclusion: Adolescent patients with schizophrenia treated with lurasidone demonstrated significant improvement in symptoms, quality of life, and function. Lurasidone was generally well tolerated and associated with minimal changes in weight and metabolic parameters. Sponsored by Sunovion Pharmaceuticals Inc. ClinicalTrials.gov identifier: NCT01911429

Dataset Information

Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia.

Publications

Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia.

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