title: Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions?
abstract: Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCA) is established in the treatment of depression to optimize outcome and safety. However, there are few reports on TDM under naturalistic clinical conditions. In the present study, we investigated a TDM group (TDM) and a randomly assigned parallel group without TDM (no-TDM) while on TCA treatment. Serum levels were analyzed in both cohorts, but feedback and dose recommendation were only provided for the TDM group. Serum levels of TCA were assessed by high-performance liquid chromatography (HPLC). The outcome was measured weekly using the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impressions Scale (CGI), and the UKU side-effect scale. 84 patients with depressive disorder according to DSM-IV were recruited in three centers (TDM, n = 43; no-TDM, n = 41; mean age 49.9 +/- 13.2 years, 63.1 % female). Patients were treated with either amitriptyline (n = 69) or doxepin (n = 15); the mean dosage at endpoint was 126 +/- 35 mg and 155 +/- 47 mg, respectively. The mean study duration was 21 +/- 8 days. Both groups improved according to HAMD (from 25.2 +/- 8.4 at baseline to 12.0 +/- 7.4 at endpoint) and CGI scores (68 % responders). Moderately severe or severe side effects occurred in 16 % of patients. Adequate dose adjustment was significantly higher in the TDM group (60 % vs. 46 %, p < 0.05); this led to a significantly higher rate of therapeutic serum levels in the TDM group (58 % vs. 44 %, p < 0.05). Direct effects of TDM were not found for effectiveness. Therapeutic TCA serum levels over weeks one to three, however, were associated with significantly better outcome at endpoint (p < 0.05) as measured with changes in the HAMD or CGI response rates from baseline to endpoint. Finally, considerable side effects occurred significantly more often when serum levels were above the therapeutic range (27 % vs. 11 %; p < 0.01). We conclude that treating depression with TCA can be optimized by early TDM, which is superior to clinical judgment on its own. Since the psychiatrists in charge were less than completely "compliant" to the recommendations provided together with serum levels, the effect could be more pronounced than this study shows. The results encourage further studies in order to optimize antidepressant pharmacotherapy when using TDM appropriately.
authors.affiliation: Department of Psychiatry, University of Mainz, Mainz, Germany. mjm@mail.psychiatrie.klinik.uni-mainz.de
authors.forename: M J
authors.initials: MJ
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Dragicevic
authors.forename: M
authors.initials: M
authors.lastname: Fric
authors.forename: I
authors.initials: I
authors.lastname: Gaertner
authors.forename: K
authors.initials: K
authors.lastname: Grasmäder
authors.forename: S
authors.initials: S
authors.lastname: Härtter
authors.forename: E
authors.initials: E
authors.lastname: Hermann
authors.forename: H J
authors.initials: HJ
authors.lastname: Kuss
authors.forename: G
authors.initials: G
authors.lastname: Laux
authors.forename: W
authors.initials: W
authors.lastname: Oehl
authors.forename: M L
authors.initials: ML
authors.lastname: Rao
authors.forename: N
authors.initials: N
authors.lastname: Rollmann
authors.forename: H
authors.initials: H
authors.lastname: Weigmann
authors.forename: M
authors.initials: M
authors.lastname: Weber-Labonte
authors.forename: C
authors.initials: C
authors.lastname: Hiemke
mesh_terms: D000639:Amitriptyline / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004316:Doxepin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004316:Doxepin; D000639:Amitriptyline