title: The prevalence of duloxetine in medico-legal death investigations in Victoria, Australia (2009-2012).
abstract: 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.
authors.affiliation: Department of Forensic Medicine, Monash University, 57-83 Kavanagh Street, Southbank 3006, Victoria, Australia. Electronic address: jennifer.pilgrim@monash.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pilgrim
authors.affiliation: 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.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Gerostamoulos
authors.affiliation: 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.
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Drummer
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000097:blood*; D001315:Australia / Q000453:epidemiology; D006332:Cardiomegaly / Q000473:pathology; D002423:Cause of Death; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000473:pathology; D003334:Coroners and Medical Examiners; D004347:Drug Interactions; D000068736:Duloxetine Hydrochloride; D005260:Female; D053593:Forensic Toxicology; D006801:Humans; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000097:blood; D015995:Prevalence; D011654:Pulmonary Edema / Q000473:pathology; D053719:Tandem Mass Spectrometry; D013876:Thiophenes / Q000009:adverse effects* / Q000097:blood*
chemical_list: D000928:Antidepressive Agents; D004364:Pharmaceutical Preparations; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride
keywords: Adverse drug reaction; Antidepressant; Duloxetine; SNRI; Serotonin toxicity; Sudden death