A 38-year-old man with schizoaffective disorder is brought to the emergency department due to a 5-day history of malaise, loss of appetite, nausea, and abdominal pain. The patient was hospitalized 2 months ago for a manic episode with delusions and hallucinations, and his medication regimen was changed. Since discharge, his psychiatric condition has improved. He has no history of medical illness and does not drink alcohol or use illicit drugs. Temperature is 37.8 C (100 F), blood pressure is 100/65 mm Hg, and pulse is 98/min. Abdominal examination reveals right upper quadrant tenderness. Neurologic examination shows a fine bilateral hand tremor. On mental status examination, the patient appears drowsy but responds to questions. He is oriented to person, place, and year but not month or day. He has no suicidal ideation or auditory hallucinations, and no delusions are elicited. Laboratory results are as follows:
| Complete blood count | |
| Hematocrit | 42% |
| Platelets | 180,000/mm3 |
| Leukocytes | 9,200/mm3 |
| Serum chemistry | |
| Blood urea nitrogen | 18 mg/dL |
| Creatinine | 1.0 mg/dL |
| Liver function studies | |
| Total bilirubin | 2.1 mg/dL |
| Alkaline phosphatase | 110 U/L |
| Aspartate aminotransferase | 360 U/L |
| Alanine aminotransferase | 520 U/L |
Which of the following medications is most likely responsible for the findings in this patient?
This patient's symptoms of malaise, anorexia, and nausea and findings of right upper quadrant abdominal tenderness and elevated aminotransferases are consistent with liver injury. This, in the absence of underlying liver disease, is most likely due to drug-induced liver injury.
Among the psychotropic medications listed, hepatotoxicity is most commonly associated with the anticonvulsant mood stabilizer valproate. Serious or fatal hepatotoxicity may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, anorexia, and/or nausea. Most cases occur during the first 6 months of treatment. Patients receiving valproate should have liver tests prior to therapy and regularly thereafter. In addition to hepatotoxicity, valproate is also associated with tremor, thrombocytopenia, and alopecia.
(Choice A) The antidepressant bupropion is associated with increased risk of seizures.
(Choice B) Clozapine, used in treatment-resistant schizophrenia/schizoaffective disorder, is associated with the risk of severe neutropenia.
(Choice C) Haloperidol is less likely to cause liver injury. The low-potency antipsychotic chlorpromazine has been associated with cholestatic jaundice.
(Choice D) Lamotrigine can cause serious rashes, including Stevens-Johnson syndrome.
(Choice E) Lithium is not metabolized and is excreted almost exclusively through the kidneys. It is associated with effects on renal and thyroid function.
(Choice F) Trazodone has been associated with the rare adverse effect of priapism.
Educational objective:
The anticonvulsant mood stabilizer valproate can cause elevated aminotransferases and in rare cases hepatic failure, most commonly in the first 6 months of treatment.