A fatality due to serotonin syndrome

Serotonin syndrome is most commonly seen in patients receiving two agents that increase the availability of serotonin by different methods, commonly a serotonin reuptake inhibitor (SSRI) and a monamine oxidase inhibitor (MAOI). We report a rare fatality in a patient who ingested Isocarboxazid in addition to a SSBI and a tricyclic antidepressant (TCA). A 56-year-old woman with a history of depression on Nortriptyline, Sertraline, and Fluoxetine presented after several hours of diaphoresis and tremulousness. On physical examination, her temperature was 100°F, heart rate was 108, respiratory rate was 28, and blood pressure was 110/60. She had rigors and was agitated; she was also diaphoretic but her mental status was intact. The remainder of her physical examination was unremarkable. The initial electrocardiogram was within normal limits except for sinus tachycardia. The laboratory data were normal except for a CPK of 922 with a MB index of 2. Within four hours her temperature climbed to 106.8°F. Aggressive supportive therapy was instituted that included acetaminophen, antibiotics, benzodiazepines, fluids, intubation, and passive cooling. A second electrocardiogram showed right bundle branch block and changes consistent with an acute inferior ischemic injury that was followed by refractory ventricular fibrillation and death. Autopsy revealed mild to moderate atherosclerotic lumen narrowing without coronary occlusion. Prior to her demise we were told she had also taken Isocarboxazid. Postmortem blood levels were: 97 ng/ml for benzylhydrazine (an isocarboxazid metabolite) 1.24 mcg/ml N-desmethysertraline, .33 mcg/ml fluoxeline, 1.79 mcg/ml sertraline, and 0.58 mcg/ml nortriptyline. We document a patient coingesting a MAOI, a TCA, and two SSRIs, and postulate this combination may have caused hyperthermia complicated by coronary vasospasm. A fatal case of serotonin syndrome is reported in which coronary vasospasm secondary to drug interaction is suspected.