Clinical significance of plasma levels of clomipramine, its hydroxylated and desmethylated metabolites: prediction of clinical outcome in mood disorders using discriminant analysis of therapeutic drug monitoring data.

We measured the plasma concentrations of clomipramine and its metabolites, N-desmethylclompiramine, 8-hydroxy-N-desmethylclomipramine, 8-hydroxyclomipramine in 65 depressed patients with subtypes of DSM-III-R mood disorders receiving clomipramine hydrochloride. There were large interindividual variations in the concentrations of the parent and each of the metabolic compounds, though the overall correlations between drug concentrations and daily doses of clomipramine were highly significant. Metabolic ratios for both desmethylation and hydroxylation varied by 15-35-fold interindividually. Discriminant analysis of the data from drug concentrations and scores of Global Assessment of Functioning revealed that it is useful to monitor the concentrations of both desmethylated and hydroxylated metabolites in order to predict the clinical effects of clomipramine.