Effects of Amitriptyline and Imipramine on Amine Metabolites in the Cerebrospinal Fluid of Depressed Patients

The effect of tricyclic antidepressant treatment on the metabolism of brain serotonin and dopamine was evaluated in depressed patients by studying levels of the respective metabolites (5-hydroxyindoleacetic acid [5HIAA] and homovanillic acid [HVA]) in the cerebrospinal fluid (CSF) after the administration of probenecid. probenecid causes rapid accumulation of 5HIAA and HVA by inhibiting transport out of the CSF, thus providing a measure of amine turnover. Treatment with amitriptyline hydrochloride and imipramine hydrochloride was associated with a reduced accumulation of 5HIAA, whereas, HVA accumulation was not affected. These findings suggest that, in depressed patients, central nervous system serotonin turnover is decreased during treatment with amitriptyline and imipramine.