lurasidone-hydrochloride and Sleep-Initiation-and-Maintenance-Disorders

Lurasidone, an atypical antipsychotic, is a potent 5-HT7 antagonist and D2 , 5-HT2A antagonist, and 5-HT1A partial agonist. As such, lurasidone would be expected to modulate sleep and circadian function but there have been no human studies of the sleep effects of a 5-HT7 antagonist. The purpose of this study was to assess effects of lurasidone on sleep.. This was a cross-over, polysomnographic study involving 54 healthy volunteers who underwent two treatment periods (order randomized) each consisting of two nights in the laboratory: Night 1-lights out at usual bedtime; Night 2-4-h advance of sleep phase and randomization to either lurasidone 40 mg or placebo. The next morning impairment testing was carried out.. Lurasidone significantly (p < 0.05) increased total sleep time by an average of 28.4 min versus placebo, decreased wake time after sleep onset and wake time after the final awakening, and increased sleep efficiency. No other effects were found.. Lurasidone had a sleep maintenance effect without effects on sleep onset, rapid eye movement, or slow-wave sleep. Lurasidone is likely to be beneficial to patients with disturbed sleep, particularly those with sleep maintenance problems. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Antipsychotic Agents; Cross-Over Studies; Double-Blind Method; Female; Humans; Lurasidone Hydrochloride; Male; Polysomnography; Receptors, Serotonin; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Sleep Initiation and Maintenance Disorders; Sleep Stages

Topics: Adolescent; Anticonvulsants; Antipsychotic Agents; Azepines; Bipolar Disorder; Humans; Lurasidone Hydrochloride; Male; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Triazoles; Valproic Acid

To evaluate the long-term safety and tolerability of lurasidone in schizophrenia and schizoaffective disorder patients switched to lurasidone.. Patients in this multicenter, 6-month open-label, flexible-dose, extension study had completed a core 6-week randomized trial in which clinically stable, but symptomatic, outpatients with schizophrenia or schizoaffective disorder were switched to lurasidone. Patients started the extension study on treatment with the same dose of lurasidone taken at study endpoint of the 6-week core study; following this, lurasidone was flexibly dosed (40-120 mg/day), if clinically indicated, starting on Day 7 of the extension study. The primary safety endpoints were the proportion of patients with treatment emergent adverse events (AEs), serious AEs, or who discontinued due to AEs. Secondary endpoints included metabolic variables and measures of extrapyramidal symptoms and akathisia, as well as the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), and the Calgary Depression Scale for Schizophrenia (CDSS). The study was conducted from August 2010 to November 2011.. Of the 198 patients who completed the 6-week core study, 149 (75.3%) entered the extension study and 148 received study medication. A total of 98 patients (65.8%) completed the 6-month extension study. Lurasidone 40, 80, and 120 mg were the modal daily doses for 19 (12.8%), 65 (43.9%), and 64 (43.2%) of patients, respectively. Overall mean (SD) daily lurasidone dose was 102.0 mg (77.1). The most commonly reported AEs were insomnia (13 patients [8.8%]), nausea (13 patients [8.8%]), akathisia (12 patients [8.1%]), and anxiety (9 patients [6.1%]). A total of 16 patients (10.8%) had at least one AE leading to discontinuation from the study. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, lipids, glucose, insulin, or prolactin. Movement disorder rating scales did not demonstrate meaningful changes. Treatment failure (defined as any occurrence of discontinuation due to insufficient clinical response, exacerbation of underlying disease, or AE) was observed for 19 patients (12.8% of patients entering) and median time to treatment failure was 58 days (95% CI 22-86). The discontinuation rate due to any cause was 50/148 (33.8%), and median time to discontinuation was 62 days (95% CI 30-75). The mean PANSS total score, mean CGI-S score, and mean CDSS score decreased consistently from core study baseline across extension visits, indicating an improvement in overall condition.. In this 6-month, open-label extension study, treatment with lurasidone was generally well-tolerated with sustained improvement in efficacy measures observed in outpatients with schizophrenia or schizoaffective disorder who had switched to lurasidone from a broad range of antipsychotic agents.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Anxiety; Drug Substitution; Female; Humans; Lurasidone Hydrochloride; Male; Middle Aged; Nausea; Prospective Studies; Psychotic Disorders; Schizophrenia; Sleep Initiation and Maintenance Disorders; Treatment Outcome