lurasidone-hydrochloride and Psychotic-Disorders

Serotonin syndrome (SS) is a life-threatening condition, usually precipitated by a combination of serotonergic agents. Data regarding the incidence and management of SS in obstetrics are limited. This study presents a case of SS provoked by an atypical antipsychotic in a second trimester, singleton gestation, and reviews the management of SS in an obstetric patient. We present a case of a schizophreniform, pregnant patient with a singleton gestation admitted to a community, military hospital for serotonin syndrome. The patient was admitted to the intensive care unit (ICU) by the obstetrics team, where she was managed conservatively. The cornerstones of therapy were as follows: discontinuation of offending agent, intravenous fluids, supplemental oxygen, telemetry, and hourly neurological assessments. Fetal status was monitored daily. After stabilization, the patient was transferred from the ICU to inpatient psychiatry for continued care. Although serotonin syndrome is infrequently encountered in obstetrics, it is paramount that all obstetricians are familiar with its recognition and management, particularly in community hospital settings. The low incidence of reported SS is largely attributed to under-recognition, as the syndrome can mimic other more common obstetric diagnoses such as preeclampsia. Given the increasing prevalence of mental health disorders, it is essential for obstetricians to be aware of the potential for SS in our patient population.

Topics: Adult; Antipsychotic Agents; Emergence Delirium; Female; Humans; Intensive Care Units; Lurasidone Hydrochloride; Pregnancy; Psychotic Disorders; Serotonin Syndrome

Lurasidone ([3aR,4S,7R,7aS]-2-[(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1yl-methyl] cyclohexylmethyl]-hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride; Latuda®) is a novel benzisothiazole, second-generation antipsychotic drug developed by Dainippon Sumitomo Pharma Corporation in Japan. Similar to other atypical antipsychotics it has a distinctive pharmacodynamic profile, Areas covered: This review updates reported research findings on the efficacy, safety and tolerability of LRSD for treatment of psychotic and major affective disorders, with meta-analyses. Short-term efficacy of LRSD in schizophrenia is supported by several randomized, controlled trials with daily doses of 40-160 mg, yielding relatively modest symptomatic improvements. Lurasidone has regulatory approval for treatment of undefined duration in schizophrenia. Long-term benefits and effects in schizophrenia, and both short- and long-term use for other psychotic disorders and mania have not been tested. LRSD shows unusual efficacy in acute bipolar depression even without psychotic features. However, trials of adding LRSD to lithium or valproate for bipolar disorder have yielded inconsistent findings. Expert opinion: Available research findings indicate that LRSD is effective and well-tolerated for short-term treatment of schizophrenia, and for acute bipolar depression. It has low risk of inducing weight-gain, metabolic, or cardiac abnormalities, but its risk of akathisia may exceed that of other modern antipsychotics. Needed is adequate long-term testing in schizophrenia and bipolar disorder and testing for other indications, including against alternative treatments.

Topics: Antipsychotic Agents; Bipolar Disorder; Dose-Response Relationship, Drug; Humans; Lurasidone Hydrochloride; Mood Disorders; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia

To perform a systematic review of studies of lurasidone in children and/or adolescents and to present a case report aimed to add further insights into its use in clinical practice with youth.. We searched the following databases for empirical studies, of any design, focusing on the pharmacokinetics, efficacy, or safety of lurasidone in children and/or adolescents: Pubmed (Medline), OVID (PsycInfo, EMBASE+EMBASE classic, OVID Medline), Web of Knowledge, and ClinicalTrials.gov (last search January 23, 2018).. From a pool of 301 potentially relevant references, we retained 12 pertinent studies (reported in 28 references), including 1 pharmacokinetics study, 1 double blind randomized controlled trial (RCT) for bipolar depression (BD) with 1 related interim analysis study of its extension phase and 1 related external posterior predictive check study, 1 double blind RCT for schizophrenia with 3 related interim analyses of its extension phase, 1 RCT and 1 case report for autism spectrum disorder, and 2 open-label studies focusing on a variety of disorders. Overall, these studies show that lurasidone is significantly more efficacious than placebo, with moderate effect sizes, and is well tolerated for BD and schizophrenia in youth. Published studies in youth have in general used doses up to 80 mg/day. Our case report suggests that high doses of lurasidone (148 mg/day) were well tolerated and might have contributed to substantial functional improvement in a 14-year old girl with psychosis and a previous history of anorexia nervosa, who had not responded to previous antipsychotics (olanzapine, risperidone, aripiprazole).. There is increasing evidence that lurasidone may be moderately effective and well tolerated for the treatment of BD and psychosis in youth and may have procognitive effects. Our case report suggests that future RCTs should assess the efficacy and tolerability of high doses (>80 mg/day) of lurasidone in youth.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Female; Humans; Lurasidone Hydrochloride; Psychotic Disorders; Schizophrenia

Second-generation antipsychotics (SGA) are new treatment options for bipolar disorders (BDs). Lurasidone is one such SGA, which is currently approved as a monotherapy for bipolar I depression (BPID) and as an add-on therapy for acute schizophrenia.. In this drug evaluation, the authors illustrate the pharmacological profile of lurasidone and review its development history. The aim of this review is to evaluate whether this compound could be used in psychotic BDs.. The pharmacological profile of lurasidone, its action on receptors, its role in neurogenesis and its cognitive performance suggests a potential use in psychotic episodes of BDs and mania. This hypothesis is also supported by the clinical observations from case reports concerning resolutions of BPID with psychotic features, where psychotic episodes were diagnosed as schizophrenia and reclassified as BDs after the patient was able to reconstruct his/her clinical history. The use of lurasidone may have the advantage of a low side-effect profile and a possible efficacy in preventing the impairment of cognitive performance. However, randomized clinical trials assessing the efficacy of lurasidone in the treatment of manic episodes as well as manic episodes with psychotic components are still needed.

Topics: Animals; Antipsychotic Agents; Bipolar Disorder; Humans; Isoindoles; Lurasidone Hydrochloride; Psychotic Disorders; Schizophrenia; Thiazoles

Antipsychotic medications are the foundation of the pharmacological treatment of schizophrenia and lurasidone is the most recent of the 65 agents around the world to become available. In order to use it optimally, it is important to understand its pharmacological and clinical nature and its comparative effectiveness to other antipsychotic agents in the treatment of schizophrenia.. Following a comprehensive review of the literature, this article summarizes current information about the pharmacology of lurasidone, data about its short- and long-term efficacy and safety/tolerability in the treatment of schizophrenia, its comparative effectiveness to other antipsychotic agents, and guidance about its optimal use in the treatment of individuals with schizophrenia.. Lurasidone is a benzoisothiazole with potent dopamine D2 and serotonin 5HT2A antagonist and serotonin 5HT1A partial agonist properties (like other second-generation antipsychotic agents) with additional potent 5HT7 and alpha2C noradrenergic antagonism. It has little or no activity at the alpha1 and alpha2A noradrenergic, 5HT2C serotonergic, histaminergic and cholinergic receptors. Available only in an oral formulation, it is effective in once-daily dosing (40 - 160 mg/day) and its absorption is affected by food. There is an extensive clinical trial database with short-term and long-term placebo- and antipsychotic-controlled clinical trials evaluating the efficacy and safety/tolerability of lurasidone in the treatment of schizophrenia. It has been found to be efficacious with comparable efficacy to other agents in the treatment of acute psychosis and prevention of relapse in individuals with schizophrenia. The greater antidepressant and cognitive benefits suggested by its receptor profile need substantiation in robust clinical trials. It is less likely to cause metabolic and cardiac adverse effects than most other second-generation agents and is associated with a modest risk of extrapyramidal side-effects, akathisia, and prolactin elevation.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Humans; Lurasidone Hydrochloride; Psychotic Disorders; Recurrence; Schizophrenia

Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive. In this review, we focus primarily on the data supporting the use of second-generation, atypical antipsychotics both at high doses and in combination with other antipsychotics.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brain; Clozapine; Dibenzocycloheptenes; Drug Therapy, Combination; Heterocyclic Compounds, 4 or More Rings; Humans; Impulsive Behavior; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone; Thiazoles; Violence

Small-scale studies of auditory processing cognitive remediation programs have demonstrated efficacy in schizophrenia. We describe a multicenter, rater-blinded, randomized, controlled study of auditory-focused cognitive remediation, conducted from June 24, 2010, to June 14, 2013, and approved by the local institutional review board at all sites.. Prior to randomization, participants with schizophrenia (DSM-IV-TR) were stabilized on a standardized antipsychotic regimen (lurasidone [40-160 mg/d]), followed by randomization to adjunctive cognitive remediation: auditory focused (Brain Fitness) versus control (nonspecific video games), administered 1-2 times weekly for 30 sessions. Coprimary outcome measures included MATRICS Consensus Cognitive Battery (MCCB) and the University of California, San Diego, Performance-Based Skills Assessment-Brief scale.. 120 participants were randomized and completed at least 1 auditory-focused cognitive remediation (n = 56) or video game control session (n = 64). 74 participants completed ≥ 25 sessions and postrandomization assessments. At study completion, the change from prestabilization was statistically significant for MCCB composite score (d = 0.42, P < .0001) across groups. Participants randomized to auditory-focused cognitive remediation had a trend-level higher mean MCCB composite score compared to participants randomized to control cognitive remediation (P = .08). After controlling for scores at the time of randomization, there were no significant between-treatment group differences at study completion.. Auditory processing cognitive remediation combined with lurasidone did not lead to differential improvement over nonspecific video games. Across-group improvement from prestabilization baseline to study completion was observed, but since all participants were receiving lurasidone open label, it is difficult to interpret the source of these effects. Future studies comparing both pharmacologic and behavioral cognitive enhancers should consider a 2 × 2 design, using a control for both the medication and the cognitive remediation.. ClinicalTrials.gov identifier: NCT01173874.

Topics: Adolescent; Adult; Auditory Perceptual Disorders; Cognitive Remediation; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Lurasidone Hydrochloride; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Young Adult

OBJECTIVE/INTRODUCTION: Lurasidone is an atypical antipsychotic medication approved for the treatment of schizophrenia over a dose range of 40-160 mg/day. This study examined D2 receptor occupancy and its association with clinical improvement and side effects in patients with schizophrenia or schizoaffective disorder following repeated doses of 80, 120, or 160 mg/day of lurasidone.. Twenty-five patients with The Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnoses of schizophrenia or schizoaffective disorder were washed out of their antipsychotic medications (5 half-lives) and randomly assigned to 80, 120, or 160 mg/day of lurasidone. Subjects were imaged with 18F-fallypride at baseline and at steady-state lurasidone treatment to determine D2 receptor occupancy.. Blood lurasidone concentration (plus major metabolite), but not dose, significantly correlated with D2 receptor occupancy. D2 receptor occupancy in several subcortical structures is associated with positive but not negative symptom improvement or the presence of movement symptoms.. Blood concentrations greater than 70 ng/mL may be required to achieve a 65% occupancy level in subcortical areas. Intersubject blood concentrations at fixed dose were highly variable and may account for the lack of dose correlations.. Positron emission tomography (PET) occupancy data suggest that greater than 65% occupancy can be achieved across the dose range of 80-160 mg/day and that some patients require higher doses to achieve antipsychotic efficacy; this finding supports prior randomized clinical trial results.

Topics: Adult; Algorithms; Antipsychotic Agents; Benzamides; Brain; Dose-Response Relationship, Drug; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Positron-Emission Tomography; Psychiatric Status Rating Scales; Psychotic Disorders; Pyrrolidines; Receptors, Dopamine D2; Schizophrenia; Statistics as Topic; Thiazoles; 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

To examine the effectiveness of switching patients to lurasidone using 3 different dosing strategies.. Adults with DSM-IV-defined schizophrenia or schizoaffective disorder in a nonacute phase of illness were randomized to 1 of 3 lurasidone dosing regimens for the initial 2 weeks of the study: (1) 40 mg/d for 2 weeks; (2) 40 mg/d for 1 week, increased to 80 mg/d on day 8 for week 2 (up-titration group); and (3) 80 mg/d for 2 weeks. Lurasidone was then flexibly dosed (40-120 mg/d) for the subsequent 4 weeks of the study. The preswitch antipsychotic agent was tapered by day 7 to 50% of the original dose and discontinued by the end of week 2. Subjects were stratified on the basis of whether the primary preswitch antipsychotic medication was classified as "sedating" (olanzapine or quetiapine) or "nonsedating" (all other antipsychotics). The primary outcome measure was time to treatment failure, defined as any occurrence of insufficient clinical response, exacerbation of underlying disease, or discontinuation due to an adverse event. The study was conducted from June 2010 to May 2011.. Of 240 subjects treated in this study, 86 (35.8%) were treated with an antecedent sedating antipsychotic, and 154 (64.2%) were treated with an antecedent nonsedating antipsychotic. Nineteen (7.9%) of the 240 patients experienced treatment failure. No clinically relevant differences were observed when the 3 randomized switch groups were compared. Treatment failure rates were 10/86 (11.6%) versus 9/154 (5.8%) among subjects who had been receiving a preswitch sedating versus nonsedating antipsychotic medication, respectively. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, glucose, insulin, lipids, or prolactin; mean improvements in weight and lipids were observed. Movement disorder rating scales did not demonstrate meaningful changes. The incidence of akathisia as an adverse event was 12.5%; only 1 subject (0.4%) discontinued due to akathisia.. Switching patients to lurasidone can be successfully accomplished by starting at 40 mg/d for 2 weeks, or 80 mg/d for 2 weeks, or 40 mg/d for 1 week followed by 80 mg/d the second week.. ClinicalTrials.gov identifier: NCT01143077.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Time Factors; Treatment Failure; Treatment Outcome

Improving cognitive functioning in people with schizophrenia is a major treatment goal. In addition, interview-based measures have been developed to supplement performance-based assessments. However, few data are available regarding whether interview-based measures are sensitive to treatment-related changes.. Adult outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomized to 21 days of double-blind treatment with lurasidone 120 mg once daily (N=150) or ziprasidone 80 mg BID (N=151). A similar proportion of patients completed the study on lurasidone (67.5%) and ziprasidone (69.3%). Study participants were assessed with the majority of the tests from the MATRICS Consensus Cognitive Battery (MCCB) and an interview-based assessment of cognitive functioning, the Schizophrenia Cognition Rating Scale (SCoRS). SCoRS ratings were based on the interviewer's best judgment, after interviews with the patient and a caregiver when available. The study was conducted from April 2006 to January 2007.. There were no between-group treatment differences in performance on the MCCB or the SCoRS ratings. Lurasidone patients demonstrated significant within group-improvement from baseline on the MCCB composite score (p=0.026) and on the SCoRS (p<0.001), but ziprasidone patients did not improve on either the MCCB composite (p=0.254) or the SCoRS (p=0.185). At endpoint there was a statistical trend (p=0.058) for lurasidone to demonstrate greater improvement from baseline in SCoRS ratings. Improvements in interview-based aspects of cognition were not related to MCCB test changes, and had minimal correlations with changes in symptoms.. These data suggest that interview-based cognitive measures such as the SCoRS may be sensitive to changes after 3weeks of treatment in patients with schizophrenia. Lurasidone is being assessed further in ongoing clinical trials with additional outcome measures.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Interview, Psychological; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Thiazoles; Young Adult

Lurasidone is a new atypical antipsychotic agent with high affinity for D(2), 5-HT(2A) and 5-HT(7) receptors. The current study evaluated the safety and efficacy of lurasidone and ziprasidone in stable outpatients diagnosed with schizophrenia or schizoaffective disorder.. Adult outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder that was chronic (≥6 months duration) and stable were randomized to 21 days of double-blind treatment with a fixed dose of lurasidone 120 mg once daily (N=150) or ziprasidone 80 mg BID (N=151). Changes from baseline in efficacy measures were evaluated using mixed model for repeated measures (MMRM) analyses.. The proportion of patients who discontinued from the study was similar for lurasidone and ziprasidone (32.5% vs. 30.7%); the proportion who discontinued due to adverse events was similar (10.4% vs. 11.1%). Treatment with lurasidone and ziprasidone was associated with a small endpoint reduction in median weight (-0.65 kg vs. -0.35 kg) and median total cholesterol (-6.4 vs. -4.4 mg/dL); no endpoint change was observed in median triglycerides (0.0 vs. 0.0 mg/dL). There were no clinically significant changes in other laboratory or ECG parameters. Improvement was observed on an MMRM analysis of the PANSS total score for lurasidone and ziprasidone at Week 1 (-4.1 vs. -1.6; P=0.020), Week 2, (-6.1 vs. -3.6; P=0.074), and Week 3 (-6.3 vs. -4.5; P=0.229).. In this double-blind, fixed-dose comparison of lurasidone 120 mg and ziprasidone 160 mg, treatment with lurasidone was well-tolerated and safe, and was not associated with clinically significant changes from baseline in weight, metabolic parameters, or QTc interval. Study limitations include the relatively short trial duration and lack of placebo control.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Body Weight; Cholesterol; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Outpatients; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Thiazoles; Time Factors; Treatment Outcome; Triglycerides; Young Adult

Lurasidone is an atypical antipsychotic approved for the treatment of schizophrenia and bipolar depression. It seems to have an antidepressant effect due to 5-HT7 as well as 5-HT2A and 5-HT1a receptor affinity. Here we present a case of a 19-year-old male patient with first-episode psychosis (FEP) and predominant depressive symptoms. Remarkable clinical and functional improvement was observed 3 months after the beginning of lurasidone treatment. The patient's depressive symptoms disappear with a dramatic reduction of psychotic ones, with good tolerance of the drug and without adverse effects. Lurasidone seems to be a promising treatment option for FEP with predominant depressive symptoms.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depression; Humans; Lurasidone Hydrochloride; Male; Psychotic Disorders; Young Adult

This case is one of the earliest to report on lurasidone-related QTc prolongation in a dose-dependent fashion in CAP population at therapeutic doses. Although these reports remain scarce, it behoves prescribers to be vigilant and mindful of these unusual but serious side effects especially in setting of cumulative risks.

Topics: Antipsychotic Agents; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Humans; Long QT Syndrome; Lurasidone Hydrochloride; Psychotic Disorders

Topics: Aged; Antipsychotic Agents; Exanthema; Female; Humans; Lurasidone Hydrochloride; Psychotic Disorders

Topics: Antipsychotic Agents; Female; Humans; Lurasidone Hydrochloride; Middle Aged; Neuroleptic Malignant Syndrome; Psychotic Disorders

We present the case of a woman with bipolar I disorder with severe premenstrual mood instability, confusion, and psychosis resembling the clinical features of postpartum psychosis when estrogen levels are expected to be low, and hypomania when estrogen levels are expected to be elevated. While depressive symptoms across the menstrual cycle have been extensively documented in the literature, there is little information regarding manic and hypomanic symptoms. In addition, we describe the successful treatment of her menstrual-cycle related symptoms. Approaches to the management of menstrual psychosis have not been systematically studied, and clinical guidelines do not exist. Clinical experiences such as the one reported here, in which the clinical formulation of the patient was consistent with known neuroendocrine phenomena and in which the treatment approach was successful, are crucial to developing promising approaches that can be tested in controlled trials.

Topics: Affect; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Lithium; Lurasidone Hydrochloride; Menstrual Cycle; Premenstrual Syndrome; Psychotic Disorders; Treatment Outcome; Valproic Acid; Young Adult

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

Topics: Antipsychotic Agents; Cyclooxygenase 2 Inhibitors; Dibenzocycloheptenes; Evidence-Based Medicine; Heterocyclic Compounds, 4 or More Rings; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Isoindoles; Isoxazoles; Lactones; Lurasidone Hydrochloride; Piperidines; Psychotic Disorders; Pyridines; Serotonin Receptor Agonists; Sulfones; Thiazoles