Spencer C M, Wilde M I
Adis International Limited, Auckland, New Zealand.
Drugs. 1998 Sep;56(3):405-27. doi: 10.2165/00003495-199856030-00010.
Milnacipran is a cyclopropane derivative which acts by inhibiting noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake at presynaptic sites; no postsynaptic receptor activity has been demonstrated. It is most commonly administered at a dosage of 50 mg twice daily for the treatment of major depressive disorder. Improvement usually occurs within 2 weeks of treatment initiation, but some patients do respond sooner. Most studies which evaluated milnacipran were of short (4 to 8 weeks) duration and results were not published in full with rigorous peer review. Nonetheless, the drug is significantly more effective than placebo for the treatment of in- or outpatients with moderate to severe major depressive disorder. Limited data suggest that it may prevent relapse and be effective for long term use, although this requires confirmation. Milnacipran 200 mg/day is generally not significantly different from amitriptyline 150 mg/day in terms of onset and efficacy. However, when doses are titrated (not a requirement for milnacipran), milnacipran 50 or 100 mg/day has a slower onset than the tricyclic antidepressant. At a dosage of 100 mg/day for 4 to 12 weeks, milnacipran generally has similar efficacy to imipramine and clomipramine 150 mg/day, although milnacipran 50 to 150 mg/day had a faster onset of activity than imipramine 50 to 150 mg/day in Japanese patients. In a 6-month trial, milnacipran was less effective than clomipramine. Milnacipran 50 or 100 mg twice daily was as effective as fluoxetine 20 mg once daily or fluvoxamine 100 mg twice daily in 4- to 12-week studies. At a dosage of 50 then 100 mg daily it was also as effective as mianserin 30 then 60 mg daily in a 4-week study. However, when administered once daily (in the evening), milnacipran 100 mg/day was not as effective as fluoxetine 20 mg/day after 6 weeks. The drug is generally well tolerated, producing no more adverse events (including anticholinergic events) than placebo, selective serotonin reuptake inhibitors or mianserin and fewer adverse events than tricyclic antidepressants in clinical trials. However, dysuria has been reported in 7% of male patients receiving milnacipran.
Data from predominantly short term trials suggest that milnacipran generally has similar efficacy to tricyclic antidepressants and SSRIs. Although further published data are required to confirm its efficacy, good tolerability profile and pharmacokinetic profile which suggests a low potential for drug interactions, milnacipran should be considered a promising agent for the treatment of patients with major depressive disorder.
米那普明是一种环丙烷衍生物，其作用机制是抑制突触前位点的去甲肾上腺素（去甲肾上腺素）和5-羟色胺（5-羟色胺；5-HT）再摄取；尚未证明其有突触后受体活性。它最常用于治疗重度抑郁症，剂量通常为每日两次，每次50毫克。通常在开始治疗后2周内病情有所改善，但有些患者反应更快。大多数评估米那普明的研究持续时间较短（4至8周），且结果未经过严格的同行评审而完整发表。尽管如此，该药物在治疗中重度重度抑郁症的门诊或住院患者方面明显比安慰剂更有效。有限的数据表明它可能预防复发且长期使用有效，尽管这需要进一步证实。就起效时间和疗效而言，米那普明200毫克/天通常与阿米替林150毫克/天没有显著差异。然而，当进行剂量滴定（米那普明不需要）时，米那普明50或100毫克/天的起效比三环类抗抑郁药慢。在4至12周的剂量为100毫克/天的治疗中，米那普明通常与丙咪嗪和氯米帕明150毫克/天的疗效相似，尽管在日本患者中，米那普明50至150毫克/天的起效比丙咪嗪50至150毫克/天更快。在一项为期6个月的试验中，米那普明的疗效低于氯米帕明。在4至12周的研究中，米那普明每日两次，每次50或100毫克，与氟西汀每日一次，每次20毫克或氟伏沙明每日两次，每次100毫克的疗效相同。在一项为期4周的研究中，每日剂量为50毫克然后100毫克时，它也与米安色林每日30毫克然后60毫克的疗效相同。然而，当每日一次（晚上）给药时，米那普明100毫克/天在6周后不如氟西汀20毫克/天有效。该药物一般耐受性良好，在临床试验中产生的不良事件（包括抗胆碱能事件）不比安慰剂、选择性5-羟色胺再摄取抑制剂或米安色林多，且比三环类抗抑郁药少。然而，据报道，接受米那普明治疗的男性患者中有7%出现排尿困难。
主要来自短期试验的数据表明，米那普明的疗效通常与三环类抗抑郁药和选择性5-羟色胺再摄取抑制剂相似。尽管需要进一步发表的数据来证实其疗效、良好的耐受性和药代动力学特征（表明药物相互作用的可能性较低），但米那普明应被视为治疗重度抑郁症患者的一种有前景的药物。
