Kasper S, Dötsch M, Kick H, Vieira A, Möller H J
Department of Psychiatry, University Bonn, Germany.
Eur Neuropsychopharmacol. 1993 Mar;3(1):13-21. doi: 10.1016/0924-977x(93)90290-3.
We examined the relationship between plasma concentrations of specific acting antidepressants (fluvoxamine/maprotiline) and clinical improvement as well as the impact of the magnitude of the plasma concentration of these antidepressants on side effects. Patients (32 patients with major depression) were treated within a double-blind parallel trial for four weeks and plasma concentrations were obtained before, on days 8 and 28 of the trial. Although there was a fixed-flexible dosage design it was apparent that 16 patients (89%) of the fluvoxamine group and all patients of the maprotiline group received a dosage between 200 and 300 mg/day in the last week of the trial. Plasma concentrations (mean +/- SD micrograms/l) of fluvoxamine were 125 +/- 91 and 142 +/- 108 on days 8 and 28, respectively and the range of fluvoxamine plasma concentrations on day 28 was from 20 to 417 micrograms/l. Plasma concentrations (mean +/- SD micrograms/l) of maprotiline were 146 +/- 62 and 202 +/- 134 on days 8 and 28, respectively and the range of maprotiline plasma concentration on day 28 was from 12 to 428 micrograms/l. There was no linear relationship between plasma concentrations of both antidepressants (fluvoxamine/maprotiline) and oral dosage. Whereas there was no correlation between fluvoxamine concentration and clinical response there was a tendency that higher maprotiline concentrations were associated with a better antidepressive efficacy at the end of the trial. Higher concentrations of fluvoxamine as well as of maprotiline were significantly (P < 0.05) associated with more side effects.
我们研究了特定作用的抗抑郁药（氟伏沙明/麦普替林）的血浆浓度与临床改善之间的关系，以及这些抗抑郁药血浆浓度的大小对副作用的影响。患者（32例重度抑郁症患者）在双盲平行试验中接受了为期四周的治疗，并在试验前、第8天和第28天采集了血浆浓度。尽管采用了固定-灵活剂量设计，但很明显，在试验的最后一周，氟伏沙明组的16例患者（89%）和麦普替林组的所有患者接受的剂量在200至300毫克/天之间。氟伏沙明在第8天和第28天的血浆浓度（平均±标准差微克/升）分别为125±91和142±108，第28天氟伏沙明血浆浓度范围为20至417微克/升。麦普替林在第8天和第28天的血浆浓度（平均±标准差微克/升）分别为146±62和202±134，第28天麦普替林血浆浓度范围为12至428微克/升。两种抗抑郁药（氟伏沙明/麦普替林）的血浆浓度与口服剂量之间均无线性关系。虽然氟伏沙明浓度与临床反应之间无相关性，但在试验结束时，麦普替林浓度越高，抗抑郁疗效越好，存在这种趋势。氟伏沙明和麦普替林浓度越高，与更多的副作用显著相关（P<0.05）。
