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.
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Dr. med. Dipl.-Psych. Matthias J. Müller
Department of Psychiatry, University of Mainz
Untere Zahlbacher Straße 8
55131 Mainz
Germany
Phone: +49 (6131) 17-7363
Fax: +49 (6131) 17-6690
Email: mjm@mail.psychiatrie.klinik.uni-mainz.de