Drug therapy is integral to the management of acute psychotic episodes in patients with schizophrenia and generally is required for long-term stabilization to sustain symptom remission or control and to minimize the risk of relapse. Antipsychotic agents are the principal class of drugs used for the management of all phases of schizophrenia. Patient response and tolerance to antipsychotic agents are variable, and patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.
Lurasidone hydrochloride is an atypical antipsychotic that is administered orally in the acute treatment of schizophrenia in adults. Schizophrenia is a major psychotic disorder that frequently has devastating effects on various aspects of the patient's life and carries a high risk of suicide and other life-threatening behaviors. Manifestations of schizophrenia involve multiple psychologic processes, including perception (e.g., hallucinations), ideation, reality testing (e.g., delusions), emotion (e.g., flatness, inappropriate affect), thought processes (e.g., loose associations), behavior (e.g., catatonia, disorganization), attention, concentration, motivation (e.g., avolition, impaired intention and planning), and judgment. The principal manifestations of this disorder usually are described in terms of positive and negative (deficit) symptoms and, more recently, disorganized symptoms. Positive symptoms include hallucinations, delusions, bizarre behavior, hostility, uncooperativeness, and paranoid ideation, while negative symptoms include restricted range and intensity of emotional expression (affective flattening), reduced thought and speech productivity (alogia), anhedonia, apathy, and decreased initiation of goal-directed behavior (avolition). Disorganized symptoms include disorganized speech (thought disorder) and behavior and poor attention.
The short-term efficacy of oral lurasidone in the acute management of schizophrenia was supported in 5 placebo-controlled, fixed-dose clinical trials of 6 weeks' duration in adults who met DSM-IV criteria for schizophrenia. Two of these studies included an active-control arm (olanzapine or extended-release quetiapine) to assess assay sensitivity. The studies used either the Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale derived (BPRSd) and the Clinical Global Impression severity scale (CGI-S) to assess the effects of drug treatment in improving clinical manifestations of schizophrenia. Studies 1 and 3 both evaluated 2 fixed dosages of lurasidone hydrochloride (40 or 120 mg daily), study 2 evaluated a fixed dosage of 80 mg daily, study 4 evaluated 3 fixed dosages (40, 80, or 120 mg daily), and study 5 evaluated 2 fixed dosages of the drug (80 or 160 mg daily). In all 5 studies, lurasidone was found to be more effective than placebo; however, in study 4 only the 80-mg daily dosage of lurasidone hydrochloride was found to be more effective than placebo, and neither 40 mg nor 120 mg could be distinguished from placebo. Thus, the efficacy of 40-, 80-, 120-, and 160-mg daily dosages of lurasidone hydrochloride was established in these studies as assessed by the change from baseline in the PANSS or BPRSd total scores and the CGI-S. An examination of population subgroups did not reveal any clear evidence of differential responsiveness to the drug based on age, gender, or race.
The manufacturer states that if lurasidone is used for extended periods (i.e., longer than 6 weeks) in the treatment of schizophrenia, the long-term usefulness of the drug should be reassessed periodically on an individualized basis.
(See Dosage and Administration: Dosage.)
The American Psychiatric Association (APA) considers most atypical antipsychotic agents first-line drugs for the management of the acute phase of schizophrenia (including first psychotic episodes), principally because of the decreased risk of adverse extrapyramidal effects and tardive dyskinesia, with the understanding that the relative advantages, disadvantages, and cost-effectiveness of conventional and atypical antipsychotic agents remain controversial. The APA states that, with the possible exception of clozapine for the management of treatment-resistant symptoms, there currently is no definitive evidence that one atypical antipsychotic agent will have superior efficacy compared with another agent in the class, although meaningful differences in response may be observed in individual patients. Conventional antipsychotic agents also may be an appropriate first-line option for some patients, including those who have been treated successfully in the past with or who prefer conventional agents. The choice of an antipsychotic agent should be individualized, considering past response to therapy, current symptomatology, concurrent medical conditions, other medications and treatments, adverse effect profile, and the patient's preference for a specific drug, including route of administration.
For additional information on the symptomatic management of schizophrenia, including treatment recommendations and results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) research program, .
Depressive Episodes Associated with Bipolar Disorder
Lurasidone hydrochloride is used orally as monotherapy or adjunctive therapy with lithium or valproate for the treatment of major depressive episodes associated with bipolar I disorder (bipolar depression) in adults.
The short-term efficacy of lurasidone monotherapy in the treatment of depressive episodes associated with bipolar I disorder was established in a randomized, double-blind, placebo-controlled, multicenter study of 6 weeks' duration in adults who met DSM-IV-TR criteria for major depressive episodes associated with bipolar I disorder, with or without rapid cycling and without psychotic features. The primary and key secondary end points were the change from baseline to week 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impressions-Bipolar-Severity of Illness scale (CGI-BP-S) scores, respectively. Patients were randomized to receive lower-dose lurasidone hydrochloride (flexible dosage range of 20-60 mg daily), higher-dose lurasidone hydrochloride (flexible dosage range of 80-120 mg daily), or placebo. Lurasidone substantially reduced MADRS and CGI-BP-S scores at week 6 of therapy in both lurasidone dosage groups compared with placebo. The higher-dose range (80-120 mg daily) of lurasidone hydrochloride was not found to be more effective, on average, than the lower-dose regimen in this study.
The short-term efficacy of lurasidone as adjunctive therapy with lithium or valproate in the treatment of depressive episodes associated with bipolar I disorder was established in a randomized, double-blind, placebo-controlled, multicenter study of 6 weeks' duration in adults who met DSM-IV-TR criteria for major depressive episodes associated with bipolar I disorder, with or without rapid cycling and without psychotic features. Patients who remained symptomatic after lithium or valproate therapy were randomized to receive flexible-dose lurasidone hydrochloride (20-120 mg daily) or placebo. The primary end point was the change from baseline to week 6 in the MADRS score, and the secondary end point was the change from baseline to week 6 in the CGI-BP-S score. Lurasidone given as adjunctive therapy with lithium or valproate substantially reduced MADRS and CGI-BP-S scores at week 6 of therapy compared with placebo.
Clinical experience with lurasidone indicates that the drug is less likely to cause weight gain and to adversely affect metabolic parameters than some other atypical antipsychotic agents (e.g., olanzapine, quetiapine) that are used in the treatment of bipolar depression. Therefore, lurasidone may be a suitable alternative treatment for patients with bipolar depression who are at higher risk of metabolic abnormalities (e.g., those with diabetes mellitus or hyperlipidemia).
The manufacturer states that the efficacy of lurasidone for longer-term use (i.e., longer than 6 weeks) in bipolar depression has not been established in controlled studies. If lurasidone is used for extended periods, the long-term usefulness of the drug should be periodically reassessed on an individualized basis.
(See Dosage and Administration: Dosage.)
The manufacturer states that the efficacy of lurasidone in the treatment of mania associated with bipolar disorder has not been established.