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Acute Massive Pulmonary Thromboembolism Due to Acute Intoxication by Duloxetine: A Case Report

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Abstract

Duloxetine (Cymbalta) is a potent serotonin norepinephrine reuptake inhibitor used for the management of major depression and pain associated with diabetic peripheral neuropathy. Cymbalta delayed-release capsules contain Duloxetine HCl equivalent to 20, 30, 60 mg of Duloxetine. The ingestion of high quantities of Duloxetine may have serious outcomes such as venous thrombosis, causing cardiac respiratory arrest. The Authors outline a case report of an elderly woman, suffering from depression, found dead in her apartment. The cause of death was attributed to acute massive pulmonary thromboembolism due to acute intoxication of Duloxetine bought the day before. The thesis supported by the authors and confirmed by the data from other studies is that a massive intake of Duloxetine drug increases considerably the medication’s side effects such as somnolence, dry mouth, fatigue, insomnia, dizziness, constipation, considerable increases in recumbent systolic and diastolic blood pressure, and a small decrease in heart rate.

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Notes

  1. David Robertson, David Wong, a co-discoverer of fluoxetine, and Joseph Krushinski are listed as inventors on the patent application filed in 1986 and granted in 1990. The first publication on the discovery of the racemic form of duloxetine known as LY227942, was made in 1988. The (+)-enantiomer of LY227942, assigned LY248686, was chosen for further studies, because it inhibited serotonin reuptake in rat synaptosomes two times more potently than (–)-enantiomer. This molecule was subsequently named duloxetine.

  2. The efficacy of Cymbalta as a treatment for depression was established in 4 randomized, double-blind, placebo-controlled, fixed-dose studies in adult outpatients (18–83 years), meeting DSMIV criteria for major depression. In 2 studies, patients were randomized to Cymbalta 60 mg once daily (N = 123 and N = 128, respectively) or placebo (N = 122 and N = 139, respectively) for 9 weeks; in the third study, patients were randomized to Cymbalta 20 or 40 mg twice daily (N = 89) for 8 weeks; in the fourth study, patients were randomized to Cymbalta 40 or 60 mg twice daily (N = 95 and N = 93, respectively) or placebo (N = 93) for 8 weeks. There is not evidence that doses greater than 60 mg/day confer additional benefits. In all 4 studies, Cymbalta demonstrated superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAMD17) total score. In all of these clinical studies, analyses of the relationship between treatment outcome and age, gender, and race did not suggest any differential responsiveness on the basis of these patient characteristics. In another study, 533 patients meeting DSMIV criteria for MDD received Cymbalta 60 mg once daily during an initial 12-week open-label treatment phase. Two hundred and seventy-eight patients who responded to open-label treatment (defined as meeting the following criteria at weeks 10 and 12: a HAMD17 total score ≤9, Clinical Global Impressions of Severity ≤2, and not meeting the DSMIV criteria for MDD) were randomly assigned to continuation of Cymbalta at the same dose (N = 136) or to placebo (N = 142) for 6 months. Patients on Cymbalta experienced a statistically significant longer time to relapse of depression than did patients on placebo. Relapse was defined as an increase in yhe CGIS score of ≥2 points compared with that obtained at week 12, as well as meeting the DSMIV criteria for MDD at 2 consecutive visits at least 2 weeks apart, where the 2-week temporal criterion had to be satisfied at only the second visit.

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Authors and Affiliations

  1. Division of Forensic Toxicology, Department of Anatomy, Histology and Forensic Medicine, University of Florence, Largo Brambilla Street 3, 50134, Florence, Italy

    Francesco Mari & Elisabetta Bertol

  2. Division of Forensic Medicine, Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy

    Barbara Gualco & Regina Rensi

Authors
  1. Francesco Mari
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  2. Barbara Gualco
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  3. Regina Rensi
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  4. Elisabetta Bertol
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Correspondence to Francesco Mari.

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Mari, F., Gualco, B., Rensi, R. et al. Acute Massive Pulmonary Thromboembolism Due to Acute Intoxication by Duloxetine: A Case Report. Cardiovasc Toxicol 12, 258–262 (2012). https://doi.org/10.1007/s12012-012-9159-x

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