Department of Clinical Pharmacology, Bispebjerg Hospital , Copenhagen , Denmark.
Clin Toxicol (Phila). 2014 Jan;52(1):39-43. doi: 10.3109/15563650.2013.862258. Epub 2013 Dec 9.
In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units.
The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population.
The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death.
Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.
2012 年，丹麦精神病学家对高剂量奥氮平治疗患者的应用提出了担忧。本研究是丹麦首都地区精神卫生服务机构对这一主题进行审计的一部分。目的：评估高剂量奥氮平（>40 毫克/天）治疗住院精神病患者的潜在风险。
本研究是一项基于病历回顾的观察性病例系列研究。主要纳入标准是在 2012 年 1 月 1 日至 3 月 15 日期间，指数入院期间至少有一次每日剂量>40 毫克奥氮平的治疗。为了针对最有可能因奥氮平治疗而发生不良反应的患者亚组，还应用了另外 6 项标准。医师医嘱输入系统和包含患者诊断和治疗具体信息的中央患者登记册用于识别研究人群。
纳入研究的 91 例患者接受的奥氮平最大日剂量范围为 45 至 160 毫克，25%的患者的总抗精神病药物负荷超过 2000 毫克氯丙嗪当量。锥体外系症状和镇静是最常见的不良反应，发生率分别为 27%和 25%。此外，在一些患者中还观察到其他已知的不良反应，如体重增加（14%）、低血压（2%）、恶性综合征（2%）和校正 QT 间期（QTc）延长（1%）。有 5 例患者死亡，其中 2 例死亡被认为与奥氮平有关。
每天接受高达 160 毫克奥氮平治疗的患者，锥体外系症状和镇静的发生频率增加，毒性作用也更为严重。为了防止不良后果，如果发生奥氮平的毒性作用，临床医生应准备采取适当措施。如果出现恶性综合征等严重不良反应，应立即停止治疗。
