Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease

Arch Neurol. 2006 Apr;63(4):521-7. doi: 10.1001/archneur.63.4.521.


Objective: To compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery.

Design: A randomized, double-blind, controlled, 2-arm study of 48 patients with the neurologic presentation of Wilson disease. Patients either received 500 mg of trientine hydrochloride 2 times per day or 20 mg of tetrathiomolybdate 3 times per day with meals and 20 mg 3 times per day between meals for 8 weeks. All patients received 50 mg of zinc 2 times per day. Patients were hospitalized for 8 weeks, with neurologic and speech function assessed weekly; discharged taking 50 mg of zinc 3 times per day, and returned annually for follow-up.

Setting: A university hospital referral setting.

Patients: Primarily newly diagnosed patients with Wilson disease presenting with neurologic symptoms who had not been treated longer than 4 weeks with an anticopper drug.

Intervention: Treatment with either trientine plus zinc or tetrathiomolybdate plus zinc.

Main outcome measures: Neurologic function was assessed by semiquantitative neurologic and speech examinations. Drug adverse events were evaluated by blood cell counts and biochemical measures.

Results: Six of 23 patients in the trientine arm and 1 of 25 patients in the tetrathiomolybdate arm underwent neurologic deterioration (P<.05). Three patients receiving tetrathiomolybdate had adverse effects of anemia and/or leukopenia, and 4 had further transaminase elevations. One patient receiving trientine had an adverse effect of anemia. Four patients receiving trientine died during follow-up, 3 having shown initial neurologic deterioration. Neurologic and speech recovery during a 3-year follow-up period were quite good.

Conclusion: Tetrathiomolybdate is a better choice than trientine for preserving neurologic function in patients who present with neurologic disease.

Trial registration: NCT00004339.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anemia / chemically induced
  • Anemia / physiopathology
  • Chelating Agents / administration & dosage*
  • Chelating Agents / adverse effects
  • Copper / antagonists & inhibitors
  • Copper / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Hepatolenticular Degeneration / drug therapy*
  • Hepatolenticular Degeneration / physiopathology
  • Humans
  • Length of Stay
  • Male
  • Middle Aged
  • Molybdenum / administration & dosage*
  • Molybdenum / adverse effects
  • Serum Albumin / drug effects
  • Serum Albumin / metabolism
  • Speech / drug effects
  • Speech / physiology
  • Speech Disorders / drug therapy
  • Speech Disorders / physiopathology
  • Treatment Outcome
  • Trientine / administration & dosage*
  • Trientine / adverse effects
  • Zinc / therapeutic use


  • Chelating Agents
  • Serum Albumin
  • Copper
  • Molybdenum
  • tetrathiomolybdate
  • Zinc
  • Trientine

Associated data