Appropriate treatments for agitation associated with schizophrenia: Control of acute agitation and maintenance of efficacy

Abstract

The first challenge in the treatment of acute agitation associated with schizophrenia is to control agitation without excessively sedating the patient, while also treating the symptoms of schizophrenia. Although oral formulations of antipsychotics have shown efficacy in the treatment of agitation, some agitated patients may not be able to take oral drugs and it may be necessary to use an intramuscular form of medication. Intramuscular formulations of benziodiazepines, typical antipsychotics and, more recently, atypical antipsychotics, have all proved effective first-line therapies for the rapid control of agitation associated with psychotic disorders. Although widely used, intramuscular benzodiazepines have been associated with excessive sedation, and typical antipsychotics, such as intramuscular haloperidol, have a high propensity for causing acute extrapyramidal symptoms. Distressing side effects may adversely impact on patient acceptance of, and adherence to, future antipsychotic therapy. Intramuscular atypical antipsychotics may provide superior alternative treatments owing to improved safety and tolerability versus typical agents. Clinical studies have demonstrated the safety and efficacy of intramuscular formulations of aripiprazole, olanzapine and ziprasidone for the treatment of agitation associated with schizophrenia, and these agents have been approved for use in the USA and some European countries. Although rapid control of agitation is the primary goal, the longer-term effects of antipsychotic therapy also require consideration. Patients initially treated with an intramuscular antipsychotic will typically transition to oral therapy for the long-term management of their disorder. Therefore, the long-term safety and tolerability of oral therapy is important. For example, treatment-associated sedation can adversely affect patient quality of life and social integration during longer-term treatment, whereas treatment with antipsychotics that are associated with significant risk of weight gain, glucose dysregulation and dyslipidaemia may have serious implications for long-term patient health. Transferring from an intramuscular to an oral antipsychotic may impose a risk of the emergence of adverse effects, breakthrough symptoms and loss of therapeutic advantage, particularly if transitioning between intramuscular and oral formulations of different antipsychotics; ideally, continuation with the same agent would minimise this risk.