Beasley C M, Koke S C, Nilsson M E, Gonzales J S
Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Clin Ther. 2000 Nov;22(11):1319-30. doi: 10.1016/s0149-2918(00)83028-3.
A 1993 meta-analysis of US Investigational New Drug clinical trials of fluoxetine reinforced this agent's more favorable adverse-event profile compared with tricyclic antidepressants (TCAs).
The present meta-analysis sought to provide a reanalysis of updated adverse-event and discontinuation data for fluoxetine 20 to 80 mg/d compared with TCAs and placebo in the treatment of major depressive disorder (MDD) in adults. A subanalysis to assess the safety profile of the most commonly used effective dose of fluoxetine in MDD (20 mg) was also conducted.
Data were obtained from 25 double-blind clinical trials involving 4016 patients with MDD randomized to treatment with fluoxetine 20 to 80 mg/d, TCAs, or placebo. The subanalysis included data from 6 trials involving 1258 patients treated with fixed 20-mg doses of fluoxetine or placebo. Spontaneously reported treatment-emergent adverse events, reasons for discontinuation, and events leading to discontinuation were compared between groups.
The age of the 4016 randomized patients ranged from 12 to 90 years, with a mean age of 46 years. Most patients were white (92%), and 62% were female. The age of the 1258 patients in the 20-mg fixed-dose population ranged from 18 to 90 years, with a mean age of 54 years; as in the total population, most of these patients were white (92%), and 57% were female. The adverse-event profiles of fluoxetine and TCAs in these trials were consistent with the typical profiles of selective serotonin reuptake inhibitors and TCAs. At a dose of 20 mg/d, fluoxetine-treated patients had a discontinuation rate due to adverse events that was not statistically significantly different from that in placebo recipients. Discontinuation rates due to lack of efficacy were not significantly different between fluoxetine and TCAs. However, significantly more TCA-treated patients discontinued therapy because of adverse events and significantly fewer completed treatment compared with fluoxetine-treated patients (both, P < 0.001). The most common events (> or = 2%) leading to discontinuation were asthenia, dizziness, insomnia, nausea, nervousness, somnolence, and tremor in fluoxetine-treated patients and abnormal vision, agitation, constipation, dizziness, dry mouth, headache, nausea, nervousness, rash, somnolence, sweating, and tremor in TCA-treated patients.
Data from this large series of clinical trials confirm that fluoxetine is well tolerated in the acute treatment of MDD in adults, especially at a dosage of 20 mg/d, and is better tolerated than the recommended doses of TCAs.
1993年一项对美国氟西汀研究性新药临床试验的荟萃分析强化了该药物与三环类抗抑郁药（TCA）相比更有利的不良事件特征。
本荟萃分析旨在重新分析氟西汀20至80mg/d与TCA及安慰剂相比治疗成人重度抑郁症（MDD）的最新不良事件和停药数据。还进行了一项亚分析以评估MDD中最常用有效剂量（20mg）氟西汀的安全性。
数据来自25项双盲临床试验，涉及4016例随机接受20至80mg/d氟西汀、TCA或安慰剂治疗的MDD患者。亚分析纳入了6项试验的数据，涉及1258例接受固定20mg剂量氟西汀或安慰剂治疗的患者。比较了各组间自发报告的治疗中出现的不良事件、停药原因及导致停药的事件。
4016例随机分组患者的年龄为12至90岁，平均年龄46岁。大多数患者为白人（92%），62%为女性。20mg固定剂量组中1258例患者的年龄为18至90岁，平均年龄54岁；与总体人群一样，这些患者大多数为白人（92%），57%为女性。这些试验中氟西汀和TCA的不良事件特征与选择性5-羟色胺再摄取抑制剂和TCA的典型特征一致。在20mg/d剂量时，氟西汀治疗的患者因不良事件导致的停药率与安慰剂组相比无统计学显著差异。氟西汀和TCA因疗效不佳导致的停药率无显著差异。然而，与氟西汀治疗的患者相比，TCA治疗的患者因不良事件停药的显著更多，完成治疗的显著更少（均P<0.001）。导致氟西汀治疗患者停药的最常见事件（≥2%）为乏力、头晕、失眠、恶心、紧张、嗜睡和震颤，TCA治疗患者为视力异常、激越、便秘、头晕、口干、头痛、恶心、紧张、皮疹、嗜睡、出汗和震颤。
这一大系列临床试验的数据证实，氟西汀在成人MDD的急性治疗中耐受性良好，尤其是在20mg/d的剂量时，且耐受性优于推荐剂量的TCA。
