Agitation in schizophrenia: origins and evidence-based treatment

Abstract

Purpose of reviewAgitation associated with schizophrenia remains an important clinical concern and if not managed effectively, can escalate into aggressive behavior. This is a review of the recent biomedical literature on agitation in individuals with schizophrenia. Recent findingsThemes in the recent literature include consideration of comorbidities such as cigarette smoking and cannabis use. Surveys reveal that pharmacological approaches to manage agitation have changed little, with haloperidol remaining in common use and intramuscular administration of antipsychotics and/or benzodiazepines being frequently administered to more severely agitated/aggressive individuals. Of note, ketamine has been recently adopted for use in severe agitation in medical emergency departments, but the risk of this medication for people with schizophrenia is unclear. At present, inhaled loxapine remains the only rapidly acting noninjectable FDA-approved treatment for agitation associated with schizophrenia. In development is an intranasal formulation for olanzapine (a well characterized atypical antipsychotic already approved to treat agitation) and a sublingual film for dexmedetomidine (an a2-adrenergic agonist used as an anesthetic and now being repurposed). SummaryComorbidities can contribute to agitation and can make an accurate differential diagnosis challenging. The ongoing development of rapidly acting novel formulations of antiagitation medications, if successful, may facilitate clinical treatment by providing additional options.

Finding the Right Setting for the Right Treatment During the Acute Treatment of Individuals with Schizophrenia: A Narrative Review and Clinical Practice Guideline

“…Short-acting injectable antipsychotics should be utilized as a last resort alternative, and second-generation antipsychotics are preferrable from a side effect perspective. 30 , 48 , 49 Predominance of cognitive symptoms: In an acute episode, the degree of cognitive impairment may be difficult to assess (one would have to rely on informant reports), and in some cases, safety must be prioritized in the acute setting. When possible, it is recommended to avoid sedating and anticholinergic medications and medications that may cause extrapyramidal symptoms and worsen cognitive deficits.…”

Alternative Approaches for Addressing Acute Agitation in Schizophrenia and Bipolar Disorder

“…21,22 Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, has been used for in-hospital and emergency department treatment of agitation, though its use is associated with elevated rates of sedation and need for intubation and potential for worsening of psychosis. [25][26][27][28][29] Table 1. For patients with schizophrenia or bipolar disorder, antipsychotics are preferred over benzodiazepines, as they address the underlying psychiatric disorder.…”

“…21,23,30 IM second-generation antipsychotics are superior to IM haloperidol in terms of tolerability and perhaps efficacy, but administration of IM haloperidol remains common. 29 For individuals with dementia, antipsychotics have been used "offlabel" as a treatment of agitation, as-needed use of IM olanzapine and aripiprazole has been studied in registrational studies, and on-going use (not "as needed") of oral brexpiprazole has received US Food and Drug Administration (FDA) approval for the treatment of agitation associated with dementia due to Alzheimer's disease. [31][32][33][34] Benzodiazepines are commonly used when an initial dose of an antipsychotic does not adequately control the agitation or if acute withdrawal from alcohol or sedatives is suspected.…”

Mengenali Dan Tata Laksana Agitasi Pada Skizofrenia Di Instalasi Gawat Darurat Rumah Sakit

“…Perbandingan obat-obat tersebut dapat dilihat pada tabel di bawah ini. 9,16 Tabel 2 Antipsikotik Atipikal Lorazepam merupakan pilihan yang paling sering digunakan dari golongan benzodiazepin. Hal ini disebabkan penyerapannya yang cepat, onset dalam waktu 60-90 menit dan dapat bertahan 8-10 jam.…”