Life-threatening serotonin syndrome in a patient with chronic heart failure and CYP2D6*1/*5.
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.
Sato
Akinori
A
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Okura
Yuji
Y
Minagawa
Shiroh
S
Ohno
Yukiko
Y
Fujita
Satoru
S
Kondo
Daisuke
D
Hayashi
Manabu
M
Komura
Satoru
S
Kato
Kiminori
K
Hanawa
Haruo
H
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
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
D019389:Cytochrome P-450 CYP2D6; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors