Critical appraisal of lurasidone in the management of schizophrenia

Istituto di Ricerche Farmacologiche, "Mario Negri", Milan, Italy.
Neuropsychiatric Disease and Treatment (Impact Factor: 1.74). 04/2012; 8:155-68. DOI: 10.2147/NDT.S18059
Source: PubMed


Lurasidone is a new atypical antipsychotic in the benzoisothiazoles class of chemicals. Like most second-generation antipsychotics it is a full antagonist at dopamine D(2) and serotonin 5-HT(2A) receptors, and is a partial agonist at 5-HT(1A) receptors, a property shared by some but not all older agents. It has much greater affinity for 5-HT(7) subtype receptors than other atypical antipsychotics. Pharmacokinetic studies showed that lurasidone is reasonably rapidly absorbed, with bioavailability appearing to be increased by food. Lurasidone undergoes extensive metabolism to a number of metabolites, some of which retain pharmacological activities. Metabolism is mainly by CYP3A4, resulting in steady-state concentrations that vary between individuals and are potentially affected by strong inducers and inhibitors of this enzyme. Short-term clinical trials have demonstrated the efficacy of lurasidone in acute schizophrenia, with doses of 40 and 80 mg/day giving significant improvements from baseline in the PANSS and BPRS scores. The most common adverse events are nausea, vomiting, akathisia, dizziness, and sedation, with minimal increases in the risk of developing metabolic syndrome. Lurasidone did not raise the risk of QTc interval prolongation, although additional studies are required. Long-term trials are also needed to assess the risk of new-onset diabetes. Ongoing trials in patients with bipolar disorder are being completed but, again, efficacy and safety have been investigated only in a few short-term clinical trials.

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    • "Lurasidone’s safety, so far, has been assessed in short-term clinical trials and in a few long-term trials of lurasidone among schizophrenia or schizoaffective disorder patients.36–40 The clinical trials among bipolar disorder patients are currently being completed; however, limited evidence exists regarding the safety of lurasidone among these populations.24 Preliminary findings based on several short-term studies among schizophrenia patients suggest that lurasidone is tolerable and safe with a low discontinuation rate.24 "
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    ABSTRACT: Lurasidone is a benzisothiazol derivative and an atypical antipsychotic approved by the US Food and Drug Administration for the acute treatment of adults with schizophrenia (October 2010) and bipolar 1 depression (June 2013). Lurasidone has a strong antagonistic property at the D2, serotonin (5-HT)2A, and 5-HT7 receptors, and partial agonistic property at the 5-HT1A receptor. Lurasidone also has lower binding affinity for the α2C and 5-HT2C receptor. Lurasidone is rapidly absorbed (time to maximum plasma concentration: 1-3 hours), metabolized mainly by CYP3A4 and eliminated by hepatic metabolism. In two large, well-designed, 6-week trials in adult patients with bipolar 1 depression, lurasidone monotherapy and adjunctive therapy with mood stabilizers were significantly more effective than placebo at improving depressive symptoms assessed using the Montgomery-Åsberg Depression Rating Scale total score. In both trials, lurasidone also reduced the Clinical Global Impression-Bipolar Severity depression score to a greater extent than placebo. In these two trials, discontinuation rates due to adverse events in the lurasidone group were small (<7%) and were not different from those of the placebo group. The most common adverse events in the lurasidone group were headache, nausea, somnolence, and akathisia. The changes in lipid profiles, weight, and parameters of glycemic control were minimal, and these findings were in line with those observed in schizophrenia trials. Further active comparator trials and long-term tolerability and safety data in bipolar patients are required. Lurasidone may be an option for the management of depressive symptoms in patients with bipolar 1 disorder, and it may be considered as a treatment alternative for patients who are at high risk for metabolic abnormalities.
    Neuropsychiatric Disease and Treatment 10/2013; 9:1521-1529. DOI:10.2147/NDT.S51910 · 1.74 Impact Factor
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    Neuropsychiatric Disease and Treatment 07/2012; 8:321-2. DOI:10.2147/NDT.S35278 · 1.74 Impact Factor
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    ABSTRACT: This article reviews the pharmacological profile and published efficacy and tolerability/safety data of iloperidone, asenapine and lurasidone, the most recent atypical antipsychotics to be approved in the USA for the treatment of schizophrenia. All three agents are similar in terms of overall efficacy and low propensity for clinically significant weight gain or adverse changes in glycemic or lipid profile. However, these agents differ from one another in terms of formulations, pharmacokinetics, and dosing and nonmetabolic adverse effect profile. For each drug, comparative and real-world effectiveness studies are lacking, as are effectiveness and safety data in elderly, young and pregnant/nursing patients. As such, the exact place of iloperidone, asenapine and lurasidone within the broader antipsychotic armamentarium is currently difficult to establish.
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