Gram L F, Pedersen O L, Kristensen C B, Bjerre M, Kragh-Sørensen P
Ther Drug Monit. 1982;4(1):17-25.
The gradual onset of action and pronounced pharmacokinetic variability provide a solid rationale for drug plasma level monitoring in psychopharmacology. For tricyclic antidepressants a well-established drug level therapeutic effect relationship is available for a few compounds (imipramine, nortiptyline, amitriptyline); and for these, plasma level monitoring can ensure more efficient and safe treatment. The relationship has been demonstrated only in endogenously depressed patients. Various pharmacokinetic problems such as dose-dependent kinetics (imipramine in elderly patients), autoinduction (chlorpromazine), drug interaction (inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants), and changes in protein binding may be better controlled by monitoring the drug levels. In amitriptyline intoxications, a possible change in the elimination kinetics results in a very slow decline in plasma levels for several days; and plasma level measurements might help to identify those patients at prolonged risk of adverse reactions. Some side effects--in particular, orthostatic hypotension--occur at subtherapeutic drug levels and therefore cannot be prevented by drug level monitoring, and monitoring of other (physiological) variables is more important. Drug level monitoring of tricyclic antidepressants thus can be considered a valuable addition to the treatment program, but it cannot replace proper clinical practice in terms of diagnostic evaluation and control of patients.
作用起效缓慢且药代动力学变异性显著，为精神药理学中监测药物血浆水平提供了坚实的理论依据。对于三环类抗抑郁药，少数几种化合物（丙咪嗪、去甲替林、阿米替林）已确立了药物水平与治疗效果的关系；对于这些药物，血浆水平监测可确保治疗更有效且安全。这种关系仅在内因性抑郁症患者中得到证实。通过监测药物水平，可更好地控制各种药代动力学问题，如剂量依赖性动力学（老年患者中的丙咪嗪）、自身诱导（氯丙嗪）、药物相互作用（抗精神病药物对三环类抗抑郁药代谢的抑制作用）以及蛋白结合的变化。在阿米替林中毒时，消除动力学的可能变化导致血浆水平在数天内非常缓慢地下降；血浆水平测量可能有助于识别那些有长期不良反应风险的患者。一些副作用——尤其是体位性低血压——在低于治疗剂量的药物水平时就会出现，因此无法通过药物水平监测预防，监测其他（生理）变量更为重要。因此，三环类抗抑郁药的药物水平监测可被视为治疗方案的一项有价值的补充，但在患者的诊断评估和管理方面，它无法取代恰当的临床实践。
