lurasidone-hydrochloride and Basal-Ganglia-Diseases

This study was designed to evaluate the short-term efficacy and safety of once-daily lurasidone (80 mg/day and 160 mg/day) in the treatment of an acute exacerbation of schizophrenia.. Participants, who were recently admitted inpatients with schizophrenia with an acute exacerbation of psychotic symptoms, were randomly assigned to 6 weeks of fixed-dose, double-blind treatment with lurasidone 80 mg (n=125), lurasidone 160 mg (n=121), quetiapine XR 600 mg (QXR-600 mg; n=119; active control included to test for assay sensitivity), or placebo (n=121), all dosed once daily in the evening. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total score (the primary efficacy measure) and Clinical Global Impressions severity (CGI-S) score (the key secondary efficacy measure).. Treatment with both doses of lurasidone or with QXR-600 mg was associated with significantly greater improvement at Week 6 on PANSS total score, PANSS positive and negative subscale scores, and CGI-S score compared with placebo. The endpoint responder rate (≥ 20% improvement in PANSS total score) was higher in subjects treated with lurasidone 80 mg (65%; p<0.001), lurasidone 160 mg (79%; p<0.001), and QXR-600 mg (79%; p<0.001) compared with placebo (41%). The proportion of patients experiencing ≥ 7% weight gain was 4% for each lurasidone group, 15% for the QXR-600 mg group, and 3% for the placebo group. Endpoint changes in levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were comparable for both lurasidone groups and placebo, while the QXR-600 mg group showed a significant median increase compared with the placebo group in levels of cholesterol (p<0.001), LDL cholesterol (p<0.01), and triglycerides (p<0.05).. Lurasidone 80 mg and 160 mg doses administered once-daily in the evening, were safe and effective treatments for subjects with acute schizophrenia, with increased response rates observed at the higher dose. Dose-related adverse effects were limited, and both doses were generally well-tolerated.

Topics: Adolescent; Adult; Aged; Akathisia, Drug-Induced; Analysis of Variance; Antipsychotic Agents; Basal Ganglia Diseases; Body Mass Index; Body Weight; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Models, Statistical; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Thiazoles; Time Factors; Waist Circumference; Young Adult

Despite the availability of established antipsychotic agents for the treatment of schizophrenia, continued unmet needs exist for effective medications with lower adverse-effect burden. The present study evaluated the efficacy, safety, and tolerability of treatment with the atypical antipsychotic lurasidone for patients with an acute exacerbation of schizophrenia. Patients were randomized to 6 weeks of double-blind treatment with lurasidone 40 mg/day, 80 mg/day, or 120 mg/day, or placebo. Changes in Positive and Negative Syndrome Scale (PANSS) scores were evaluated using mixed-model repeated-measures (MMRM) analysis. Vital signs, laboratory parameters, extrapyramidal symptoms, and electrocardiogram were assessed. Treatment with lurasidone 80 mg/day resulted in significantly greater improvement in PANSS total score compared with placebo (-23.4 versus -17.0; p < 0.05) at study endpoint (MMRM); lurasidone 40 mg/day and 120 mg/day achieved clinically meaningful overall PANSS score reductions from baseline (-19.2 and -20.5), but not significant separation from placebo. Differences between all lurasidone groups and placebo for changes in laboratory parameters and electrocardiographic measures were minimal. Weight gain ≥ 7% occurred in 8.2% of patients receiving lurasidone and 3.2% receiving placebo. Modest increases in prolactin (median increase, 0.7 ng/mL) and extrapyramidal symptoms were observed following treatment with lurasidone compared with placebo. Akathisia was the most commonly reported adverse event with lurasidone (17.6%, versus 3.1% with placebo). In this study, in which a large placebo response was observed, lurasidone 80 mg/day, but not 40 mg/day or 120 mg/day, was statistically superior to placebo in treating acute exacerbation of chronic schizophrenia. All lurasidone doses were generally well tolerated.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Basal Ganglia Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; International Cooperation; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Thiazoles; Treatment Outcome; Young Adult

Many patients with bipolar disorder are treated exclusively in primary care settings, and the use of atypical antipsychotics as primary treatment for bipolar depression is increasing. Extrapyramidal symptoms (EPS) are common side effects of antipsychotic medications, and clinicians should actively monitor for these symptoms when prescribing antipsychotic medications. Accurate diagnosis of EPS is especially important as the symptoms can be highly distressing, and in some cases, life threatening. Our aim is to familiarize primary care providers and other clinicians prescribing antipsychotic medications with EPS and to aid in its rapid diagnosis and treatment.. We describe a case of lurasidone induced dystonia with prominent laryngospasm and oculogyric crisis which was missed for many years in the primary care setting, largely due to misdiagnosis of symptoms as being related to anxiety and panic attacks.. In addition to summarizing this illustrative case, we present the most common forms of EPS and summarize the primary therapies for each type of EPS.. With increased management of bipolar disorder in the primary care setting and increased use of atypical antipsychotics as the primary therapy for bipolar disorder, it is essential that all practitioners are prepared to actively monitor for EPS, followed by its rapid diagnosis and treatment.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Humans; Laryngismus; Lurasidone Hydrochloride

To evaluate the safety and effectiveness of lurasidone in the long-term treatment of patients with schizophrenia.. Patients who completed a 6-week, double-blind (DB), placebo-controlled trial continued in a 22-month, open-label (OL) study during which they received once-daily, flexible-doses of lurasidone, 40-120 mg. Change in the Positive and Negative Syndrome Scale (PANSS) was analyzed using both observed case (OC) and last observation carried forward (LOCF) analyses.. Of the 251 patients who entered the OL extension, 51.4% completed 6 months, 36.7% completed 12 months, and 26.7% completed 22 months of OL treatment. Treatment with lurasidone was associated with a mean change from DB baseline, in weight of +0.4 kg at Month 12 (n=99), and +0.8 kg at Month 24 (n=67; OC analyses). Median change from DB baseline to Month 12 and Month 24, respectively, was -1.0 and -9.0 mg/dL for total cholesterol; 0.0 and -1.0 mg/dL for LDL; +1.0 and -11.0 mg/dL for triglycerides; and 0.0 and +0.1/% for HbA1c (OC analyses). The mean PANSS total score was 96.5 at DB baseline and 69.5 at OL baseline. The mean change from DB baseline in the PANSS total score at Month 24 was -43.6 (OC) and -28.4 (LOCF). Thirty-seven patients (14.7%) discontinued due to an adverse event (AE) during OL treatment. Three AEs occurred in ≥10% of patients: schizophrenia (12.4%), akathisia (10.8%), and somnolence (10.8%); and 19.2% reported at least one movement disorder-related AE. Discontinuations due to AEs occurred in 14.8% of patients.. In this 22-month, open-label extension study, treatment with lurasidone was associated with minimal effects on weight, glucose, lipids, and prolactin. Patients demonstrated sustained improvement in the PANSS total score for up to 24 months of lurasidone treatment.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Cholesterol; Cholesterol, LDL; Disorders of Excessive Somnolence; Dyslipidemias; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hyperprolactinemia; Longitudinal Studies; Lurasidone Hydrochloride; Male; Middle Aged; Parkinsonian Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Triglycerides; Weight Gain