title: Plasma concentrations of dothiepin and its metabolites are not correlated with clinical efficacy in major depressive illness.
abstract: Plasma concentration-antidepressant response relationships for dothiepin, nordothiepin, dothiepin-S-oxide, and nordothiepin-S-oxide were investigated in 50 patients (33 women and 17 men), who had had a major depressive episode. Depression and anxiety were assessed at the start of therapy and after 2 and 4 weeks by measurement of a Hamilton rating score for depression (HRSD), a Beck depression inventory (BECK), visual analog scores for depression (VASDEP) and anxiety (VASANX), and a physician's global (GLOBAL) score. There were significant (p < 0.001) decreases in both mean depression (32-69%) and mean anxiety (30-44%) scores at weeks 2 and 4, but there were no robust linear or polynomial correlations between percent decrease in depression or anxiety scores and plasma concentrations of dothiepin or its metabolites at week 4. It is suggested that measurement of the nordothiepin/dothiepin ratio may assist in the assessment of compliance.
authors.affiliation: Combined Unit in Clinical Pharmacology and Toxicology, University of Western Australia/State Health Laboratory Services, Nedlands.
authors.forename: K F
authors.initials: KF
authors.lastname: Ilett
authors.forename: T H
authors.initials: TH
authors.lastname: Blythe
authors.forename: L P
authors.initials: LP
authors.lastname: Hackett
authors.forename: R T
authors.initials: RT
authors.lastname: Ong
authors.forename: D A
authors.initials: DA
authors.lastname: Tannenbaum
authors.forename: T M
authors.initials: TM
authors.lastname: Clarke
mesh_terms: D000328:Adult; D001007:Anxiety / Q000188:drug therapy; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy* / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004308:Dothiepin / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011581:Psychological Tests; D011613:Psychotherapy
chemical_list: D004308:Dothiepin