Pilgrim Jennifer L, Gerostamoulos Dimitri, Drummer Olaf H
Department of Forensic Medicine, Monash University, 57-83 Kavanagh Street, Southbank 3006, Victoria, Australia.
Department of Forensic Medicine, Monash University, 57-83 Kavanagh Street, Southbank 3006, Victoria, Australia; Victorian Institute of Forensic Medicine, 57-83 Kavanagh Street, Southbank 3006, Victoria, Australia.
Forensic Sci Int. 2014 Jan;234:165-73. doi: 10.1016/j.forsciint.2013.11.009. Epub 2013 Nov 20.
The drug duloxetine (Cymbalta(®)) is a newer antidepressant which has been available in Australia since 2008. Duloxetine is a serotonin and noradrenaline reuptake inhibitor (SNRI), which is associated with adverse effects in the first 6 weeks of therapy, including tachycardia and worsening symptoms in people with advanced heart failure. It is also associated with serotonin toxicity in combination with certain drugs. Few reports have been published in the toxicology literature regarding duloxetine and its prevalence in coroners' cases. This study documents the prevalence of duloxetine in coronial cases between 2009 and 2012 and seeks to better understand the role of duloxetine in deaths where concomitant use with other drugs may cause adverse outcomes. Duloxetine was analyzed in blood specimens taken for the purpose of assisting the pathologist in determining a cause of death and analyzed using a validated LC-MS/MS method employed for overnight screening. There were 34 cases where duloxetine was detected of which 19 were attributed to drug toxicity. The median femoral blood concentration in the cohort was 0.14 mg/L (range 0.01-1.42 mg/L). Many deaths involved the concomitant use of numerous other medications; up to 13 other drugs were co-detected in a case. Over half of the deaths were attributed to fatal combined drug toxicity. SSRIs and venlafaxine that may have increased the risk of serotonin toxicity in combination with duloxetine were detected in five cases. Metoclopramide, contraindicated with duloxetine use, was detected in two cases. NSAIDs (n=11), antipsychotics (n=15) and benzodiazepines (n=14) were also commonly co-detected. Heart disease was observed in over 40% of the cohort, mostly in the form of coronary artery disease or cardiomegaly. Death involving duloxetine alone was uncommon (n=4); however with certain comorbidities and co-administered drugs, the risk of a fatal event is increased, particularly in the setting of other pro-serotonergic agents. In deaths where duloxetine is detected and the cause of death is believed to be natural or unascertained, it is essential that other serotonin drugs or inappropriate drug combinations be examined for their possible contribution to death.
度洛西汀（欣百达®）是一种新型抗抑郁药，自2008年起在澳大利亚上市。度洛西汀是一种5-羟色胺和去甲肾上腺素再摄取抑制剂（SNRI），在治疗的前6周会产生不良反应，包括心动过速以及使晚期心力衰竭患者的症状恶化。它与某些药物联用时还会引发5-羟色胺中毒。毒理学文献中关于度洛西汀及其在死因裁判案件中发生率的报道很少。本研究记录了2009年至2012年度洛西汀在死因裁判案件中的发生率，并试图更好地了解度洛西汀在与其他药物联用时可能导致不良后果的死亡案例中的作用。为协助病理学家确定死因采集了血样，并采用经过验证的用于过夜筛查的液相色谱-串联质谱法（LC-MS/MS）对血样中的度洛西汀进行分析。共检测出34例含有度洛西汀的案例，其中19例归因于药物毒性。该队列中股静脉血浓度中位数为0.14毫克/升（范围为0.01 - 1.42毫克/升）。许多死亡案例涉及同时使用多种其他药物；一个案例中最多同时检测出13种其他药物。超过半数的死亡归因于致命的联合药物毒性。在5个案例中检测出可能与度洛西汀联合使用会增加5-羟色胺中毒风险的选择性5-羟色胺再摄取抑制剂（SSRI）和文拉法辛。在2个案例中检测出与度洛西汀禁忌联用的甲氧氯普胺。非甾体抗炎药（n = 11）、抗精神病药（n = 15）和苯二氮卓类药物（n = 14）也经常被同时检测出。超过40%的队列患有心脏病，大多表现为冠状动脉疾病或心脏肥大。单独由度洛西汀导致的死亡并不常见（n = 4）；然而，在某些合并症和同时使用其他药物的情况下，致命事件的风险会增加，特别是在同时使用其他促5-羟色胺能药物的情况下。在检测出度洛西汀且死因被认为是自然原因或无法确定的死亡案例中，必须检查其他5-羟色胺类药物或不恰当的药物组合对死亡可能产生的影响。
