Battaglia John
Department of Psychiatry and Behavioural Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Drugs. 2005;65(9):1207-22. doi: 10.2165/00003495-200565090-00003.
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.
急性激越见于多种医学和精神疾病状况，严重时可导致行为失控。快速镇静是指果断使用药物迅速使严重激越的患者平静下来，减少危险行为，并便于对潜在疾病进行治疗。在过去几十年中，单独或联合使用的典型抗精神病药物和苯二氮䓬类药物的肌肉注射一直是首选治疗方法。氟哌啶醇和劳拉西泮是治疗急性激越最广泛使用的药物，在广泛的诊断领域有效，可用于有医学并发症的患者。氟哌啶醇可引起明显的锥体外系症状，很少与心律失常和猝死相关。劳拉西泮可导致共济失调、镇静，并与其他中枢神经系统抑制药物有相加作用。最近，已开发出两种非典型抗精神病药物的快速起效制剂，即肌肉注射齐拉西酮和肌肉注射奥氮平，用于治疗急性激越。肌肉注射齐拉西酮已显示对患有精神分裂症和其他非特异性精神病性状况的急性激越患者，在给药30分钟后出现显著的镇静作用。肌肉注射齐拉西酮耐受性良好，自2002年引入以来已在精神科急诊广泛使用。与其他非典型抗精神病药物相比，齐拉西酮相对更易增加校正QT（QTc）间期，因此，已知有QTc间期相关疾病的患者不应使用。在治疗与精神分裂症、分裂情感性障碍、双相躁狂和痴呆相关的急性激越方面，肌肉注射奥氮平已显示出比氟哌啶醇或劳拉西泮起效更快、疗效更好且不良反应更少。肌肉注射奥氮平已显示出有明显的镇静与非特异性镇静作用。最近有关肌肉注射奥氮平的不良事件报告（包括8例死亡）强调了遵循严格处方指南并避免与其他中枢神经系统抑制药物同时使用的必要性。一旦急性激越发作减轻，肌肉注射齐拉西酮和肌肉注射奥氮平都已显示易于过渡到同一种药物的口服治疗。尚无随机对照研究在严重激越、药物所致状态或有显著医学合并症的患者中检验这两种药物。目前的临床经验以及一项关于肌肉注射齐拉西酮的自然主义研究表明，它在这类人群中有效且可安全使用。这些肌肉注射的非典型抗精神病药物可能代表了急性激越治疗方面的一项历史性进展。
