Montgomery S A, Prost J F, Solles A, Briley M
St Mary's Hospital Medical School, London, UK.
Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:47-51. doi: 10.1097/00004850-199609004-00007.
The relative benefits and risks of milnacipran, a novel antidepressant which selectively inhibits the reuptake of serotonin and noradrenaline, have been evaluated in comparative trials against tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs). A total of 2462 patients with major depressive disorders have been investigated. At the optimal dose (50 mg twice a day), the efficacy of milnacipran was equivalent to that of the TCAs, with response rates of approximately 65% in both cases. Milnacipran was consistently effective against all of the principal elements of depression (anxiety, cognitive function, sleep and psychomotor retardation), and did not produce sedation or the emergence of suicidal thoughts. The Clinical Global Impression (CGI-3) score, a measure of the overall therapeutic impact of a treatment, was significantly higher with milnacipran than with TCAs (1.98 versus 1.84, p < 0.05). TCAs were associated with a higher frequency of adverse events than milnacipran, particularly with respect to anticholinergic-like effects; dysuria was the only adverse event occurring twice as frequently with milnacipran than with TCAs. Compared with TCAs, milnacipran was also associated with a lower incidence of cardiovascular adverse events. No haematological abnormalities occurred during treatment with milnacipran, and the incidence of abnormal liver function tests tended to be lower with milnacipran than with TCAs. In comparisons with SSRIs, milnacipran produced significantly higher response rates. The CGI-3 scores were significantly higher in milnacipran-treated patients (2.64 versus 2.32, p < 0.05). The adverse event profiles of the two treatments were similar, as was the incidence of abnormal liver function tests. These studies suggest that milnacipran offers clinical advantages over TCAs in terms of tolerability, and over SSRIs in terms of efficacy. In particular, the lack of cardiovascular adverse events appears to offer advantages in cases of deliberate overdose. To date, 15 such overdoses have occurred; none was fatal and each had a favourable outcome. The reproducible pharmacokinetic characteristics of milnacipran present further advantages over both groups of agents, due to lack of drug accumulation and a low risk of drug interactions.
米那普明是一种新型抗抑郁药，可选择性抑制5-羟色胺和去甲肾上腺素的再摄取。在与三环类抗抑郁药（TCA）或选择性5-羟色胺再摄取抑制剂（SSRI）的对比试验中，对其相对的益处和风险进行了评估。共调查了2462例重度抑郁症患者。在最佳剂量（每日两次，每次50毫克）下，米那普明的疗效与三环类抗抑郁药相当，两种药物的有效率均约为65%。米那普明对抑郁症的所有主要症状（焦虑、认知功能、睡眠和精神运动迟缓）均持续有效，且不会产生镇静作用或引发自杀念头。临床总体印象（CGI-3）评分是衡量治疗总体疗效的指标，米那普明组的该评分显著高于三环类抗抑郁药组（1.98对1.84，p<0.05）。三环类抗抑郁药的不良事件发生率高于米那普明，尤其是在抗胆碱能样效应方面；排尿困难是米那普明发生率比三环类抗抑郁药高出一倍的唯一不良事件。与三环类抗抑郁药相比，米那普明的心血管不良事件发生率也较低。米那普明治疗期间未出现血液学异常，其肝功能检查异常的发生率也往往低于三环类抗抑郁药。与选择性5-羟色胺再摄取抑制剂相比，米那普明的有效率显著更高。米那普明治疗组的CGI-3评分显著更高（2.64对2.32，p<0.05）。两种治疗的不良事件情况相似，肝功能检查异常的发生率也相似。这些研究表明，米那普明在耐受性方面优于三环类抗抑郁药，在疗效方面优于选择性5-羟色胺再摄取抑制剂。特别是，在故意过量用药的情况下，缺乏心血管不良事件似乎具有优势。迄今为止，已发生15起此类过量用药事件；无一例致命，且每例结局均良好。由于不存在药物蓄积且药物相互作用风险低，米那普明可重现的药代动力学特征比这两类药物更具优势。
