Risch S C, Huey L Y, Janowsky D S
J Clin Psychiatry. 1979 Feb;40(2):58-69.
The authors have critically reviewed the literature regarding the relationship between plasma levels of tricyclic antidepressant and their clinical efficacy. When available, drug-drug interactions, pharmacokinetics, and other factors influencing plasma levels of tricyclic antidepressants are discussed. Although many studies are confounded by significant methodological and statistical problems, it appears to these reviews that the available evidence suggests a curvilinear relationship between nortriptyline plasma levels and antidepressant efficacy in tricyclic responsive endogenously depressed inpatients, with maximal therapeutic efficacy achieved with notriptyline plasma levels between 50-175 ng/ml. The evidence for imipramine supports a linear relationship between plasma levels of imipramine plus desmethylimipramine and clinical response in nondelusional endogenously depressed tricyclic responsive inpatients. For amitriptyline, the picture is less clear. However, with the exception of one well-controlled study, the available evidence suppprts some significant relationship between amitriptyline plus nortriptyline plasma levels and antidepressant efficacy in tricyclic respoonsive endogenously depressed patients, but it is not clear as to whether this is a linear relationship or a curvilinear one. For the other antidepressants: protriptyline, desmethylimipramine, doxepin, clomipramine, maprotiline, and butriptyline, a significant relationship (if any) awaits further elucidation. It is important to point out that these plasma level relationships probably do no generalize to other types of depressions (e.g. neurotic, characterological, delusional, acute situationa, etc.) and clearly do not apply to every endogenous tricyclic responsive patient. /owever, it appears that, in general, a clinician will obtain therapeutic efficacy for endogenously depressed patients if these guidelines are followed. The actual therapeutic levels will depend on the assay's sensitivity and specificity and may vary from center to center, illustrates the importance of each center defining its own therapeutic limits, or conversely all centers adoptina a universal reproducible assay methodology for each compound measured. Despite these limitations, these reviewers feel that routine monitoring of plasma levels of the tricyclic antidepressants is a useful method to maximize therapeutic efficacy and prvent undue side effects, as well as to insure good medication compliance.
作者对有关三环类抗抑郁药血浆水平与其临床疗效之间关系的文献进行了批判性综述。如有可能，还讨论了药物相互作用、药代动力学以及影响三环类抗抑郁药血浆水平的其他因素。尽管许多研究因重大的方法学和统计学问题而混淆不清，但在这些综述看来，现有证据表明，在三环类反应性内源性抑郁住院患者中，去甲替林血浆水平与抗抑郁疗效之间呈曲线关系，去甲替林血浆水平在50 - 175 ng/ml之间时可达到最大治疗效果。关于丙咪嗪的证据支持丙咪嗪加去甲丙咪嗪血浆水平与非妄想性内源性抑郁三环类反应性住院患者的临床反应之间呈线性关系。对于阿米替林，情况不太明确。然而，除了一项严格对照的研究外，现有证据支持在三环类反应性内源性抑郁患者中，阿米替林加去甲替林血浆水平与抗抑郁疗效之间存在某种显著关系，但尚不清楚这是线性关系还是曲线关系。对于其他抗抑郁药：普罗替林、去甲丙咪嗪、多塞平、氯米帕明、马普替林和布替林，其显著关系（如果有的话）有待进一步阐明。需要指出的是，这些血浆水平关系可能不适用于其他类型的抑郁症（如神经症性、性格性、妄想性、急性情境性等），显然也不适用于每一位内源性三环类反应性患者。然而，一般来说，如果遵循这些指导原则，临床医生似乎会使内源性抑郁患者获得治疗效果。实际的治疗水平将取决于检测方法的灵敏度和特异性，并且可能因中心而异，这说明了每个中心确定自己的治疗限度的重要性，或者相反，所有中心为每种测量的化合物采用通用的可重复检测方法的重要性。尽管有这些局限性，但这些综述作者认为，常规监测三环类抗抑郁药的血浆水平是一种有用的方法，可使治疗效果最大化、预防不必要的副作用，并确保良好的药物依从性。
