Potentiation by metyrosine of thioridazine effects in chronic schizophrenics. A long-term trial using double-blind crossover technique

Arch Gen Psychiatry. 1976 Apr;33(4):501-5. doi: 10.1001/archpsyc.1976.01770040061011.


Four patients with chronic schizophrenia of stationary character were studied in order to titrate the lowest dose of thioridazine necessary for symptomatic control when the drug is given in combination with the inhibitor of catecholamine synthesis, metyrosine. The study showed 15% to 50% of the pretrial dose level of thioridazine hydrochloride was effective. In the present trial, the 779704 combination was maintained without any alterations in dosage for six months, and the therapeutic effect persisted unchanged. This treatment period was terminated by a double-blind crossover design, and the activity of metyrosine was corroborated in all cases. Plasma drug concentrations and cerebrospinal fluid amine metabolites were measured. The data indicate that schizophrenic symptoms can be profoundly influenced by changes in catecholamine synthesis. Catecholamine-carrying neurons thus seem to be fundamentally involved in those brain functions that are disturbed in schizophrenia. The clinical usefulness of metyrosine in combination with neuroleptic agents deserves more extensive investigation.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Chronic Disease
  • Clinical Trials as Topic
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Homovanillic Acid / cerebrospinal fluid
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Male
  • Methyltyrosines / administration & dosage*
  • Methyltyrosines / therapeutic use
  • Middle Aged
  • Schizophrenia / cerebrospinal fluid
  • Schizophrenia / drug therapy*
  • Thioridazine / administration & dosage*
  • Thioridazine / therapeutic use


  • Methyltyrosines
  • Hydroxyindoleacetic Acid
  • Thioridazine
  • Homovanillic Acid