Revisiting loxapine: a systematic review.

Dina Popovic,Eduard Vieta,Philippe Nuss

doi:10.1186/s12991-015-0053-3

Abstract

Loxapine is an antipsychotic used in psychiatry for over 40 years with a well-established profile. Loxapine is a dibenzoxazepine tricyclic antipsychotic agent, available for oral, intramuscular and inhalatory administration. In the light of the recent approval by the regulatory agencies of inhaled loxapine for use in the acute treatment of mild-to-moderate agitation in adults affected with schizophrenia or bipolar disorder, this article aims to critically review the available literature on loxapine, irrespective of its formulation.This review examines the efficacy and tolerability of the various formulations of loxapine in the treatment of agitation and aggression in patients affected with schizophrenia, bipolar disorder and other psychiatric conditions.A comprehensive and systematic literature search of PubMed/MEDLINE was conducted, and relevant pharmacodynamic and pharmacokinetic data was included. The findings from the literature were critically reviewed and synthesized.The available data suggests that the antipsychotic efficacy of loxapine is similar to the efficacy of other typical or atypical antipsychotics, with an adverse effects profile comparable to that of the typical antipsychotics at high doses for chronic treatment. As an acute treatment in agitation associated with schizophrenia or bipolar disorder, inhaled loxapine was developed as an innovative and rapid option which appears to be efficacious and tolerable.Electronic supplementary materialThe online version of this article (doi:10.1186/s12991-015-0053-3) contains supplementary material, which is available to authorized users.

Highlights

Loxapine, an antipsychotic that has striking similarities to clozapine, has been recently re-launched as a treatment for agitation in schizophrenia and mania
Acute agitation, characterized by motor restlessness and mental tension, is a serious medical problem that may be present in various psychiatric disorders, including schizophrenia [1] and bipolar disorder [2] and can further escalate into aggressive behaviour [3]
Mechanism of action of loxapine Loxapine is a dibenzoxazepine tricyclic antipsychotic agent, its chemical structure is similar to clozapine [13] (Figure 2) and is available for oral, intramuscular [13] and, following recent approval, inhalatory route [5]

Summary

Introduction

An antipsychotic that has striking similarities to clozapine, has been recently re-launched as a treatment for agitation in schizophrenia and mania. In addition to the timely pharmacological treatment, acute interventions that target agitation usually involve environmental and behavioural approaches [3]. In addition to morphine and scopolamine (hyoscine) combinations, barbiturates were main agents utilized to cure agitation until Delay and Deniker tested chlorpromazine. This compound was noted to be able to calm the agitation of patients with delirium, mania and psychosis even in monotherapy [5,6]. This observation was followed by numerous others, and the effectiveness of chlorpromazine in the treatment of agitated, overactive and manic states was widely confirmed [7,8]

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