[Skip to Navigation]
April 1976

Potentiation by Metyrosine of Thioridazine Effects in Chronic Schizophrenics: A Long-Term Trial Using Double-Blind Crossover Technique

Author Affiliations

From the Psychiatric Research Centre, St Jörgen Hospital and the Department of Pharmacology, University of Göteborg, Sweden.

Arch Gen Psychiatry. 1976;33(4):501-505. 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 drug combination was maintained without any alterations in dosage for six months, and the therapeutic effect persisted unchanged. This treatment period was terminated by a doubleblind 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.