Venlafaxine- and Trazodone-Induced Serotonin Syndrome

Mr. A was a 50-year old man with a past history of recurrent depression who was hospitalized for a several-week history of depression characterized by depressed mood, anhedonia, hopelessness, insomnia, and suicidal ideation. He had no psychosis or cognitive impairment. He had a history of opioid dependence since age 19, but his addiction was being treated with methadone. His past medical history was remarkable for his being seropositive for HIV for 10 years (without treatment) and seropositive for hepatitis C for 36 months. The results of laboratory tests at admission were remarkable for mildly elevated hepatic enzyme levels. Two months before admission, Mr. A’s CD4 lymphocyte level was 436 cells/μl.

Mr. A began taking extended-release venlafaxine; his dose was increased over 7 days to 225 mg/day. He also received 100 mg of trazodone at bedtime for insomnia, 100 mg t.i.d. of docusate sodium for constipation, and 120 mg/day of methadone. Eighteen days after hospitalization, Mr. A developed disorientation, restlessness, myoclonic jerking, gross tremulousness, and diaphoresis. He was afebrile; his other vital signs were unremarkable. Concurrent results of laboratory tests were not significantly different from those at admission, except for a decreased CO₂ level of 19.1 mmol/liter, an increase in aspartate aminotransferase level to 95 U/liter, and an increase in creatine kinase level to 2277 U/liter. The latter was subsequent to several intramuscular injections given to manage agitation. A computerized tomography scan of his head revealed moderate cerebral atrophy but no acute pathology. After 36 hours, during which Mr. A’s condition deteriorated, all medications were discontinued. He was given intravenous hydration. Within 24 hours his clinical status improved dramatically. He began taking methadone and docusate sodium again; he was given mirtazapine for depression. The remainder of his hospitalization was uneventful.