Asenapine, Iloperidone and Lurasidone

Critical Appraisal of the Most Recently Approved Pharmacotherapies for Schizophrenia in Adults

William V Bobo

Disclosures

Expert Rev Clin Pharmacol. 2013;6(1):61-91. 

In This Article

Abstract and Introduction

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.

Introduction

Schizophrenia is a serious, chronic psychiatric disorder with a lifetime prevalence of approximately 1% worldwide and major adverse consequences.[1] These include profound impairments in cognition, social functioning and work capacity,[2–4] and increased risk of early mortality owing to poor physical health and suicide.[5–7] Although there is currently no cure for schizophrenia, many of its most distressing clinical signs and symptoms can be managed with the long-term use of antipsychotic medication in conjunction with effective psychosocial interventions.[8]

Antipsychotic drug treatment has remained the centerpiece of both acute and long-term management of schizophrenia for the last several decades. Goals of pharmacotherapy with antipsychotic drugs include amelioration of severe psychotic symptoms (such as hallucinations, delusions, disorganized behaviors and aggression/hostility) during acute-phase treatment; prevention of acute symptom exacerbations and reduction of nonpsychotic signs and symptoms of schizophrenia (e.g., negative or 'deficit' signs and symptoms, depression, and so on) during maintenance-phase treatment; and to improve quality of life and psychosocial functioning as the overarching goal.[9]

Antipsychotic drugs are broadly classified into two groups: typical and atypical.[10] Typical and atypical antipsychotic drugs approved for clinical use in the USA share a common mechanism of action – blockade of central dopamine D2 neuroreceptors[10] – with the one exception being aripiprazole, an atypical antipsychotic and partial D2 agonist.[11] Both typical and atypical antipsychotics are effective for reducing symptoms and preventing relapse in adults with schizophrenia.[12,13] In this respect, differences in efficacy between antipsychotics is thought to be modest, with the exception of superior effectiveness of the atypical antipsychotic, clozapine, for treatment-resistant schizophrenia.[14,15] Atypical antipsychotics are distinguished clinically from typical antipsychotics by lower propensity for causing antidopaminergic side effects (including extrapyramidal symptoms [EPS] and prolactin elevation) and lower long-term risk of tardive dyskinesia at clinically relevant doses.[10] Nearly all atypical antipsychotics are potent antagonists at serotonin 5-HT2A neuroreceptors, a property not shared by the typical neuroleptics.[16]

Currently, ten atypical antipsychotic drugs are approved and marketed in the USA for the treatment of schizophrenia in adults. Of these, the most recently approved are iloperidone (FanaptTM, Vanda Pharmaceuticals, MD, USA; approved in May 2009), asenapine (SaphrisTM, Schering-Plough, Kenilworth, NJ, USA; approved in August 2009) and lurasidone (LatudaTM, Sunovion Pharmaceuticals, Inc., Marlborough, MA, USA; approved in October 2010). After a several year hiatus, these agents arrived on the market in relatively short order, with relatively limited availability outside of the USA. For example, of the three, only asenapine has regulatory approval by the EMA and in the UK for treating manic or mixed episodes associated with bipolar I disorder, although the EMA is considering an application for marketing authorization for iloperidone. As such, the role of iloperidone, asenapine and lurasidone for treating patients with schizophrenia, as well as important differences between each agent, may be unknown to many clinicians. This paper provides a review of the pharmacological properties of these three atypical antipsychotic drugs, discussed in order of approval in the USA, and the results of available published acute- and maintenance-phase studies in adults with schizophrenia. Added commentary on the place of asenapine, iloperidone and lurasidone among the other pharmacotherapeutic options for schizophrenia treatment, is also included.

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