Intramuscular aripiprazole for the treatment of agitation in schizophrenia and bipolar disorder: from clinical research to clinical practice

Aripiprazolo intramuscolare per il trattamento dell'agitazione nella schizofrenia e nel disturbo bipolare: dalla ricerca alla pratica clinica

A. Fagiolini1, S. De Filippis2, O. Azzarelli3, G. Boidi4, A. Padovan Lang5, G. Rocchetti6, V. Villari7, A. Bellomo8

1 Department of Molecular Medicine, University of Siena School of Medicine, Siena, Italy; 2 Director of Neuropsychiatric clinic Villa von Siebenthal, Genzano of Roma, Italy; and Sapienza University of Rome, II School of Medicine, Rome, Italy; 3 Department of Mental Health CT 6, ASP 3 Catania, Psychiatric Emergency Service, "S. Giovanni di Dio e S. Isidoro" Hospital, Giarre, Italy; 4 Department of Mental Health ASL 3, SPDC P.A. Micone Hospital, Sestri Ponente, Italy; 5 NHS Health Trust n. 10 Veneto Orientale, Department of Mental Health, Unit of Psychiatry, Portogruaro, Italy; 6 Director of the Department of Mental Health, ASL 7, "Umberto I" Hospital, Torrette, Italy; 7 Neuroscience and Mental Health Department, Psychiatric Emergency Service, "S. Giovanni Battista" Hospital, Turin, Italy; 8 Professor of Psychiatry, Department of Medical Sciences and Occupational Safety, Division of Psychiatry, University of Foggia, Foggia, Italy


To review the major findings of clinical research on the pharmacokinetics, therapeutic efficacy and tolerability of IM aripiprazole as a treatment option for agitation associated with schizophrenia and bipolar I disorder and to provide an expert comment based on the authors’ clinical experience in real world psychiatric practice.


Articles on intramuscular aripiprazole published in English between 1997 and 2012 were identified through a MEDLINE search. Relevant clinical studies and review articles were found using the text- and keyword-search term aripiprazole alone and in combination with intramuscular, bipolar, schizophrenia, and agitation. The reference lists of identified articles, especially review articles, were checked for any additional studies that might have been missed in the original MEDLINE search.


Acute agitation associated with schizophrenia and bipolar I disorder is a medical emergency that requires prompt pharmacological intervention to relieve patient distress and to prevent harm to self or others. Current guidelines for the management of acute agitation in schizophrenia and bipolar I disorder recommend intervention with antipsychotic agents and/or benzodiazepines, initiated as soon as possible after other conditions leading to agitation have been ruled out. Oral aripiprazole demonstrated efficacy in schizophrenia and bipolar 1 disorder (manic and mixed episodes and maintenance treatment), and resulted associated with a low risk for extrapyramidal symptoms, adverse cardiac effects, hyperprolactinemia and adverse metabolic effects. Intramuscular (IM) formulation of aripiprazole has been approved for treatment of agitation associated with schizophrenia or bipolar I disorder manic. The efficacy of IM aripiprazole in reducing agitation was assessed in two large, multinational, double-blind, placebo-controlled studies in patients with schizophrenia, schizoaffective or schizophreniform disorder 23 24, and in a similarly designed trial in patients with bipolar I disorder. IM aripiprazole was generally well tolerated in the three studies in schizophrenia and bipolar I disorder. The discontinuation rate due to adverse events was generally very low: 0.8% in the aripiprazole group versus 0.5% in the placebo group (pooled analysis). In our clinical practice, the most common reasons for choosing IM aripiprazole (apart from efficacy) are: (1) very low risk of cardiovascular events and heart conduction abnormalities; (2) relatively low risk of EPS; (3) very low risk of excessive sedation; (4) the ability to use concomitant benzodiazepines provided that careful monitoring for orthostatic hypotension is undertaken. Furthermore, based on our clinical experience, IM aripiprazole appears to act more rapidly and be more effective than oral aripiprazole in reducing acute agitation, possibly due to the higher Cmax associated with the IM formulation. However, to our knowledge, oral and IM aripiprazole have not been directly compared in a clinical trial.


IM aripiprazole is an effective treatment for agitation in patients with bipolar disorder or schizophrenia and is characterized by a relatively favorable tolerability profile.

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