Müller M J, Dragicevic A, Fric M, Gaertner I, Grasmäder K, Härtter S, Hermann E, Kuss H J, Laux G, Oehl W, Rao M L, Rollmann N, Weigmann H, Weber-Labonte M, Hiemke C
Department of Psychiatry, University of Mainz, Mainz, Germany.
Pharmacopsychiatry. 2003 May;36(3):98-104. doi: 10.1055/s-2003-39983.
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.
三环类抗抑郁药（TCA）的治疗药物监测（TDM）已应用于抑郁症治疗，以优化治疗效果和安全性。然而，关于自然临床条件下TDM的报道较少。在本研究中，我们对接受TCA治疗的TDM组和随机分配的非TDM平行组进行了调查。对两组患者的血清水平进行了分析，但仅为TDM组提供反馈和剂量建议。采用高效液相色谱法（HPLC）测定TCA的血清水平。每周使用汉密尔顿抑郁量表（HAMD）、临床总体印象量表（CGI）和UKU副作用量表进行结果测量。三个中心共招募了84例符合DSM-IV标准的抑郁症患者（TDM组，n = 43；非TDM组，n = 41；平均年龄49.9±13.2岁，女性占63.1%）。患者接受阿米替林（n = 69）或多塞平（n = 15）治疗；终点时的平均剂量分别为126±35 mg和155±47 mg。平均研究持续时间为21±8天。根据HAMD评分（从基线时的25.2±8.4降至终点时的12.0±7.4）和CGI评分，两组患者均有改善（68%的患者有反应）。16%的患者出现中度严重或严重副作用。TDM组的适当剂量调整显著更高（60%对46%，p < 0.05）；这导致TDM组的治疗性血清水平显著更高（58%对44%，p < 0.05）。未发现TDM对疗效有直接影响。然而，在第1至3周内，TCA血清治疗水平与终点时显著更好的结果相关（p < 0.05），这是通过HAMD或CGI反应率从基线到终点的变化来衡量的。最后，当血清水平高于治疗范围时，相当多的副作用显著更频繁地出现（27%对11%；p < 0.01）。我们得出结论，早期TDM可优化TCA治疗抑郁症的效果，其优于单纯的临床判断。由于负责的精神科医生并未完全“遵守”与血清水平一起提供的建议，其效果可能比本研究显示的更为显著。这些结果鼓励进一步研究，以便在适当使用TDM时优化抗抑郁药物治疗。
