PLASMA-CONCENTRATIONS OF DOTHIEPIN AND ITS METABOLITES ARE NOT CORRELATED WITH CLINICAL EFFICACY IN MAJOR DEPRESSIVE-ILLNESS

Plasma concentration-antidepressant response relationships for dothiep in, nordothiepin, dothiepin-S-oxide, and nordothiepin-S-oxide were inv estigated in 50 patients (33 women and 17 men), who had had a major de pressive episode. Depression and anxiety were assessed at the start of therapy and after 2 and 4 weeks by measurement of a Hamilton rating s core for depression (HRSD), a Beck depression inventory (BECK), visual analog scores for depression (VASDEP) and anxiety (VASANX), and a phy sician's global (GLOBAL) score. There were significant (p < 0.001) dec reases in both mean depression (32-69%) and mean anxiety (30-44%) scor es at weeks 2 and 4, but there were no robust linear or polynomial cor relations between percent decrease in depression or anxiety scores and plasma concentrations of dothiepin or its metabolites at week 4. It i s suggested that measurement of the nordothiepin/dothiepin ratio may a ssist in the assessment of compliance.