Clinical experience with dihydroxyphenylalanine (DOPA) in depression

Abstract

THIS is a report of the rGsults of a clinical trial of dihydroxyphenylalanine (DOPA), a precursor of catechol amines, in the treatment of depression. This experiment was undertaken as an indirect test of the catechol amine theory of affective disorders, which proposes that depressed patients have an absolute or relative deficiency of central nervous system (CNS) catechol amines, and that conversely, patients with elation have an excess of CNS catechol amines. The evidence in support of this theory derives from parallels between neuropharmacological investigations and clinical therapeutic experience with various psychopharmacologic agents, particularly reserpine and the MAO inhibitors. Soon after they were found effective in excited and psychotic patients, including manic patients,1 the Rauwolfia derivatives were discovered to alter CNS stored and free amines, particularly serotonin and norepinephrine. Reserpine, moreover, was found to induce severe depressive reactions in humans, especially hypertensive patients.2 Based on these considerations, BRODIE et al. proposed that the clinical and pharmacological effects of the Rauwolfia derivatives were related to their capacity to alter brain amines. The therapeutic effectiveness of iproniazid, a monoamine oxidase inhibitor, in depressions further supported the idea that depressive states might be associated with a deficiency of