Paliperidone use in probable risperidone-related liver toxicity: a case report

In the light of the recent literature, liver toxicity due to risperidone, which is a commonly used serotonin (5-HT3) and dopamine (D2) antagonist drug in the treatment of schizophrenia spectrum disorders, is a rare condition. Being the active metabolite of risperidone, paliperidone-9 hydroxy risperidone-, is majorly eliminated by renal excretion and paliperidone’s route of metabolism and elimination is different from that for risperidone. This report describes clinical outcomes of paliperidone use and improvement of liver function abnormality in a male patient whose liver function abnormality can only be described with the use of risperidone. E.C., a male patient without a previous history of any psychiatric illness, was admitted to the hospital due to auditory hallucinations, paranoid delusions, psychomotor discomfort and disturbed functioning for the last two weeks. His blood and urine laboratory tests, computed cranial tomography revealed no organic abnormalities. He was started on pharmacotherapy with the diagnosis of schizophrenia and on the 24th day of his admittance, he was discharged on risperidone 4mg poqad and biperidene 2 mg poqad. A month later, on follow up, elevation of the liver enzymes were detected (AST/SGOT=133 Unit/Liter (5-40 U/L), ALT/SGPT=344 U/L (5-40 U/L) Total bilirubin=0.7 mg/dl (0.2-1.2 mg/dl), ALP=71 U/L 35-125 U/L, LDH=377 U/L (200-450 U/L), APTT=26.988 sec). The patient had no complaints regarding gastrointestinal system and his serological markers for viral hepatitis and antinuclear antigens were negative, his abdominal ultrasound was normal. Risperidone treatment discontinued and he was started on paliperidone 6 mg poqad. During his two-week follow-ups, his liver enzymes gradually recovered (AST: 24 U/L, ALT: 34 U/L) and the levels remained normal after one year of paliperidone treatment. In clinical studies, neuropsychiatric medications account for 16 per cent of all drugs causing liver dysfunction. Different mechanisms of hepatotoxicity in psychiatric patients include alcoholism, substance abuse, and multidrug use. Paliperidone is the active metabolite of risperidone and cytochrome P450 (CYP3A4, CYP 2D6) enzyme system plays an important role in its metabolism. The majority of paliperidone is eliminated through kidney contrary to risperidone. Although the exact mechanism is not clear, elevated liver enzymes due to risperidone use might be associated with cytochrome enzyme group. When this is taken into account, switching to paliperidone might be a good choice in the case of risperidone induced liver enzyme abnormalities.