Extrapyramidal symptoms with ritonavir/indinavir plus risperidone

Ann Pharmacother. 2002 May;36(5):827-30. doi: 10.1345/aph.1A335.


Objective: To report a case of suspected extrapyramidal symptoms (EPS) in a patient initiated on ritonavir and indinavir while taking risperidone for a tic disorder.

Case summary: A 35-year-old white man with AIDS received risperidone 2 mg twice daily for treatment of a Tourette's-like tic disorder. Ritonavir and indinavir were initiated, and 1 week later, he experienced significantly impaired swallowing, speaking, and breathing, and worsening of his existing tremors. Ritonavir and indinavir were discontinued. On the same day, the patient increased the risperidone dosage to 3 mg twice daily. Symptoms continued to worsen over the next 3 days. All investigations and laboratory parameters were unremarkable, and vital signs were stable. Risperidone was discontinued and clonazepam initiated. Three days later, the patient's symptoms were significantly improved.

Discussion: The symptoms described herein are consistent with neuroleptic-induced acute dystonia and potentially neuroleptic-induced parkinsonism. We believe this adverse effect occurred as a result of a drug interaction between ritonavir/indinavir and risperidone. Based on the pharmacokinetics of these medications, we hypothesize that inhibition of CYP2D6 and CYP3A4 by ritonavir and indinavir may have resulted in an accumulation of the active moiety of risperidone, which may explain the occurrence of EPS in this patient.

Conclusions: This is the second published case report describing a suspected drug interaction with ritonavir, indinavir, and risperidone. Caution is warranted when risperidone is prescribed with ritonavir/indinavir, and possibly with other antiretrovirals that inhibit the same pathways.

Publication types

  • Case Reports

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Adult
  • Basal Ganglia Diseases / chemically induced*
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors
  • Drug Antagonism
  • Drug Therapy, Combination
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Indinavir / adverse effects*
  • Indinavir / therapeutic use
  • Male
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Risperidone / adverse effects*
  • Risperidone / therapeutic use
  • Ritonavir / adverse effects*
  • Ritonavir / therapeutic use
  • Tourette Syndrome / drug therapy


  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 Enzyme Inhibitors
  • HIV Protease Inhibitors
  • Indinavir
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Risperidone
  • Ritonavir