title: Life-threatening serotonin syndrome in a patient with chronic heart failure and CYP2D6*1/*5.
abstract: We report a case of serotonin syndrome that occurred in a patient with chronic heart failure associated with a panic disorder. The 39-year-old Japanese man had been treated with paroxetine at 20 mg/d for 1 1/2 years. He presented with rhabdomyolysis, renal failure, fulminant liver failure, cardiac conduction disturbance, and disseminated intravascular coagulation, as well as conventional symptoms of serotonin syndrome including alterations in cognition (disorientation, confusion) and behavior (restlessness), autonomic nervous system dysfunction (fever, shivering), and abnormal neuromuscular activity (ataxia, hyperreflexia, myoclonus). All medications prescribed before hospital admission were discontinued. After 24 hours of continuous venovenous hemofiltration, diuresis resumed and renal and liver function improved rapidly. Disorientation, restlessness, hyperreflexia, and myoclonus abated slowly over the next 72 hours. The patient's anxiety subsided more slowly, and he recovered completely 1 week later. The plasma concentration of paroxetine was elevated far above the upper limit of the therapeutic range. The patient had cytochrome P-450 (CYP) 2D6*1/*5, a heterozygosity of an inactivated allele of CYP2D6, which metabolizes paroxetine. The patient was determined to be an intermediate metabolizer who was potentially vulnerable to paroxetine, a major inhibitor of CYP2D6. Heart failure is often accompanied by psychiatric disorders. A wide range of drugs commonly prescribed for these conditions, including beta-blockers, antiarrhythmics, and antidepressants, are metabolized by CYP2D6. Genetic screening for CYP2D6 in patients with these conditions may prevent life-threatening drug intoxication.
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Sato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okura
authors.forename: Shiroh
authors.initials: S
authors.lastname: Minagawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ohno
authors.forename: Satoru
authors.initials: S
authors.lastname: Fujita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kondo
authors.forename: Manabu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Komura
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000328:Adult; D002908:Chronic Disease; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003937:Diagnosis, Differential; D004562:Electrocardiography; D006333:Heart Failure / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D008297:Male; D016584:Panic Disorder / Q000150:complications / Q000188:drug therapy*; D017374:Paroxetine / Q000378:metabolism; D020230:Serotonin Syndrome / Q000175:diagnosis* / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism
chemical_list: D019389:Cytochrome P-450 CYP2D6; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors