Lopez-Ibor J, Guelfi J D, Pletan Y, Tournoux A, Prost J F
Neuva Zelanda 44, Madrid, Spain.
Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:41-6. doi: 10.1097/00004850-199609004-00006.
In drug development the move from tricyclic antidepressants (TCAs) to selective serotonin reuptake inhibitors (SSRIs) involved not only the loss of the direct receptor interactions responsible for the adverse side effects of TCAs, but also the ability to inhibit the reuptake of noradrenaline. Selectivity for the single neurotransmitter, serotonin, may explain why SSRIs tend to be less efficacious than the TCAs, especially in more serious forms of depression. The advent of selective serotonin and noradrenaline reuptake inhibitors (SNRIs) has tended to confirm the idea that an action on both monoamine systems is important for maximal antidepressant efficacy. This paper reviews clinical trials comparing the new SNRI milnacipran with the SSRIs fluoxetine and fluvoxamine. A meta-analysis of the principal trials shows greater response rates (the proportion of patients with a decrease in symptom scores of 50% or more) with milnacipran (50 mg twice a day) than with fluoxetine (20 mg once a day), or fluvoxamine (100 mg twice a day) (milnacipran: 64%; SSRIs: 50%). Remission rates (the proportion of patients with Hamilton Depression Rating Scores of 7 or below) were also higher with milnacipran than with SSRIs (39 versus 28%). In one study, in which 100 mg milnacipran was given once a day in the evening, the higher response rate obtained with fluoxetine appears to be largely attributable to an inappropriate milnacipran dosage regimen. Data from a pharmacovigilance database including all patients participating in clinical trials with milnacipran (n = 5732) showed that, compared with the SSRIs, milnacipran produced fewer gastrointestinal side effects, such as nausea, and less anxiety. Milnacipran was, however, associated with a higher incidence of headache, dry mouth and dysuria. The results of these studies suggest that milnacipran is superior in efficacy to SSRIs and is equally well tolerated. Milnacipran, therefore, appears to offer a therapeutic advantage over the SSRIs.
在药物研发过程中，从三环类抗抑郁药（TCA）向选择性5-羟色胺再摄取抑制剂（SSRI）的转变，不仅意味着失去了与TCA不良副作用相关的直接受体相互作用，还丧失了抑制去甲肾上腺素再摄取的能力。对单一神经递质5-羟色胺的选择性，或许可以解释为何SSRI往往不如TCA有效，尤其是在治疗较为严重的抑郁症时。选择性5-羟色胺和去甲肾上腺素再摄取抑制剂（SNRI）的出现，倾向于证实这样一种观点，即作用于两种单胺系统对于达到最大抗抑郁疗效至关重要。本文回顾了比较新型SNRI米那普明与SSRI氟西汀和氟伏沙明的临床试验。对主要试验的荟萃分析表明，米那普明（每日两次，每次50毫克）的有效率（症状评分降低50%或更多的患者比例）高于氟西汀（每日一次，每次20毫克）或氟伏沙明（每日两次，每次100毫克）（米那普明：64%；SSRI：50%）。米那普明的缓解率（汉密尔顿抑郁量表评分7分及以下的患者比例）也高于SSRI（分别为39%和28%）。在一项研究中，米那普明每日晚上一次服用100毫克，氟西汀所获得的较高有效率似乎很大程度上归因于米那普明的剂量方案不当。来自一个药物警戒数据库的数据，该数据库涵盖了所有参与米那普明临床试验的患者（n = 5732），结果显示，与SSRI相比，米那普明产生的胃肠道副作用（如恶心）更少，焦虑症状也更少。然而，米那普明与头痛、口干和排尿困难的较高发生率相关联。这些研究结果表明，米那普明在疗效上优于SSRI，且耐受性相当。因此，米那普明似乎比SSRI具有治疗优势。
