Pharmacological Management of Acute Agitation

Abstract

Acute agitation occurs in a variety of medical and psychiatric conditions, and when severe can result in behavioural dyscontrol. Rapid tranquillisation is the assertive use of medication to calm severely agitated patients quickly, decrease dangerous behaviour and allow treatment of the underlying condition. Intramuscular injections of typical antipsychotics and benzodiazepines, given alone or in combination, have been the treatment of choice over the past few decades. Haloperidol and lorazepam are the most widely used agents for acute agitation, are effective in a wide diagnostic arena and can be used in medically compromised patients. Haloperidol can cause significant extrapyramidal symptoms, and has rarely been associated with cardiac arrhythmia and sudden death. Lorazepam can cause ataxia, sedation and has additive effects with other CNS depressant drugs.Recently, two fast-acting preparations of atypical antipsychotics, intramuscular ziprasidone and intramuscular olanzapine, have been developed for treatment of acute agitation. Intramuscular ziprasidone has shown significant calming effects emerging 30 minutes after administration for acutely agitated patients with schizophrenia and other nonspecific psychotic conditions. Intramuscular ziprasidone is well tolerated and has gained widespread use in psychiatric emergency services since its introduction in 2002. In comparison with other atypical antipsychotics, ziprasidone has a relatively greater propensity to increase the corrected QT (QTc) interval and, therefore, should not be used in patients with known QTc interval-associated conditions. Intramuscular olanzapine has shown faster onset of action, greater efficacy and fewer adverse effects than haloperidol or lorazepam in the treatment of acute agitation associated with schizophrenia, schizoaffective disorder, bipolar mania and dementia. Intramuscular olanzapine has been shown to have distinct calming versus nonspecific sedative effects. The recent reports of adverse events (including eight fatalities) associated with intramuscular olanzapine underscores the need to follow strict prescribing guidelines and avoid simultaneous use with other CNS depressants. Both intramuscular ziprasidone and intramuscular olanzapine have shown ease of transition to same-agent oral therapy once the episode of acute agitation has diminished. No randomised, controlled studies have examined either agent in patients with severe agitation, drug-induced states or significant medical comorbidity. Current clinical experience and one naturalistic study with intramuscular ziprasidone suggest that it is efficacious and can be safely used in such populations. These intramuscular atypical antipsychotics may represent a historical advance in the treatment of acute agitation.

Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens

“…3 Broadly defined as a state of motor restlessness associated with mental tension, agitation may include hand-wringing, fist clenching, pacing, pressured speech, yelling, or threatening other persons. 4 Acute agitation associated with psychiatric diseases often results in severe distress to patients and their caregivers and is a major contributor to the ongoing stigmatization of mental illness. 5 Oral loxapine, introduced more than 35 years ago in the United States, Canada, and Europe, has a well-established efficacy and safety profile in the treatment ofschizophrenia, 6,7 and an intramuscular formulation was previously approved for the treatment of agitation.…”

Післяопераційний Делірій У Пацієнтів Похилого Віку

“…Незалежно від будь-якої хвороби периферична і центральна не-рвова система страждають із віком [1]. У середньому віці відбувається втрата сірого кіркового субстрату, що призводить до церебральної атрофії [2], однак, наскільки ці зміни пов'язані зі старінням або деге-неративними захворюваннями, залишається пред-метом подальшого дослідження [3].…”

“…На нейрональному рівні фіксується зменшення складності нейронних зв'язків, зниження синтезу нейромедіаторів і збільшення активності ферментів, відповідальних за їх постсинаптичне руйнування [3][4][5]. Хоча церебральний метаболізм, потік крові і self-настройки загалом залишаються незмінними [2], нейронні втрати і дефіцит нейротрансмітерів обмежують здатність мозку інтегрувати численні нервові імпульси.…”

“…У літніх людей, осо-бливо чутливих до зниження холінергічної трансмі-сії, ризик розвитку делірію збільшується. Не можна також, безумовно, не враховувати порушення функ-ціональної активності півкуль головного мозку і та-ламуса й зниження впливу стовбурової активності ретикулярної формації [3].…”

Manejo de paciente agitado ou agressivo

“…12 However, the costs incurred in the use of second-generation antipsychotics are significantly higher for a similar efficiency profile, particularly in the management of acute situations. 13 Today, available secondgeneration antipsychotics for parenteral use in Brazil include olanzapine and ziprasidone, both to be used with and initial IM dose of 10mg and a maximum daily dose of 30mg.…”