Citalopram-Induced Long QT Syndrome and the Mammalian Dive Reflex

Abstract

<h1 class="publication-abstract-title" data-reactid=".zp4a4p04jk.1.0.6.0"> Abstract</h1> <div class="publication-abstract-text" data-reactid=".zp4a4p04jk.1.0.6.1" id="yui_3_14_1_1_1453464791844_1095"> <span class="foldable-text" data-reactid=".zp4a4p04jk.1.0.6.1.0" id="yui_3_14_1_1_1453464791844_1094">While SCUBA diving, a 44-year-old Caucasian patient had an abnormal cardiac rhythm, presumably Tor-sade de Pointes (TdP), during the initial descent to depth. Upon surfacing, she developed ventricular fibrillation and died. The patient had been treated for mild depression for nearly a year with citalopram 60 mg per day, a drug known to cause prolonged QT interval. She had also been treated with two potentially hepatotoxic drugs. Liver impairment causes selective loss of cytochrome P450 (CYP) 2C19 activity, the major pathway for metabolism of citalopram. The post mortem blood level of citalopram was 1300 ng/ mL. The patient was found to be an intermediate metabo-lizer via CYP2D6, the major pathway for metabolism of desmethylcitalopram; the level of which was also abnormally high. It is suggested that drug-induced long QT syndrome (DILQTS), caused by citalopram, combined with the mammalian dive reflex triggered malignant ventricular rhythms resulting in the patient&#39;s death. It is further suggested that, in general, the dive reflex increases the risk of fatal cardiac rhythms when the QT interval is prolonged by drugs. Key Points Long-term high dosage and impaired metabolism apparently accounted for accumulation of high, but presumably non-lethal levels, of citalopram and desmethylcitalopram in a 44-year-old woman who died while SCUBA diving.</span></div>