Mr. A, a 28-year-old Caucasian man with paranoid schizophrenia, was administered risperidone (titrated up to 8 mg/day within 5 weeks) because of a reappearance of auditory hallucinations and thought disorder after he had been free of all medications for 12 months.
After 7 weeks of outpatient risperidone monotherapy, elevated levels of serum aspartate aminotransferase (AST) (83 U/liter, normal=10–50) and alanine aminotransferase (ALT) (123 U/liter, normal=10–60) were observed. The results of cholestatic blood measurements, WBC and RBC counts, and coagulation tests were normal. Mr. A’s medical history did not reveal autoimmune or allergic disease. There was no history of alcohol or substance abuse, except occasional hashish smoking. During Mr. A’s previous hospitalization (4 years earlier), while he was receiving haloperidol, his serum transaminase levels had been normal.
His ALT and AST levels markedly increased during the 8th week of treatment (AST=139 U/liter, ALT=522 U/liter). Mr. A developed nausea, vomiting, and epigastric pain. Hospitalization was decided upon, and risperidone treatment was discontinued.
An abdominal ultrasound was normal. Serological markers for viral hepatitis A, B, and C were negative. Determinations of ceruloplasmin and copper in his serum were also normal. His WBC count showed eosinophilia (850 cells/mm3, normal<500), and laboratory analyses for autoimmune diseases revealed high levels of anti-smooth-muscle antibodies (titer=1:640), without actin or vimentin specificity. Tests for anti-liver-kidney microsomal enzymes, antisoluble liver antigen, and antinuclear and antimitochondrial auto-antibodies were negative.
With treatment consisting only of loxapine (200 mg/day) and oxazepam (200 mg/day), Mr. A’s AST and ALT levels returned to normal within 3 weeks. One month after risperidone discontinuation, his anti-smooth-muscle antibodies titer had decreased to 1:100, and his eosinophil level had returned to normal. Mr. A was then given haloperidol (20 mg/day), and his serum transaminase levels remained normal.