Clayton Anita H, Kornstein Susan G, Rosas Gregory, Guico-Pabia Christine, Tourian Karen A
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22903, USA.
CNS Spectr. 2009 Apr;14(4):183-95. doi: 10.1017/s1092852900020204.
The safety and tolerability profiles of antidepressants can often influence the treatment choices of clinicians treating major depressive disorder. The purpose of this investigation was to characterize the safety and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in treating depression.
An integrated analysis of all short-term, randomized, double-blind, placebo-controlled registration studies for major depressive disorder (four flexible-dose and five fixed-dose studies) was performed. Adult outpatients with major depressive disorder received desvenlafaxine doses ranging from 50-400 mg/day or placebo for 8 weeks. Treatment-emergent adverse events, laboratory values, vital signs, and discontinuation symptoms were evaluated. In the subset of fixed-dose studies, dose-related effects were analyzed.
In the overall population (placebo: n=1,116; desvenlafaxine: n=1,834), adverse events resulted in discontinuations in 3% of placebo-treated patients and 12% of desvenlafaxine-treated patients; in the subset of fixed-dose studies, the rates were 4% with placebo and increased with desvenlafaxine dose (50 mg/day: 4%; 400 mg/day: 18%). The most common treatment-emergent adverse event was transient nausea that was generally mild to moderate. The most common sexual dysfunction associated with desvenlafaxine treatment was erectile dysfunction in men (7% vs 1% with placebo) and anorgasmia in women (1% and 0%). One desvenlafaxine-treated patient died of a completed suicide; there were four suicide attempts (three desvenlafaxine, one placebo) and eight cases of suicidal ideation (five desvenlafaxine, three placebo) during the on-therapy period. Small but statistically significant changes in mean blood pressure occurred at all desvenlafaxine doses; clinically meaningful changes were observed in 1% of placebo-treated patients and 2% of desvenlafaxine-treated patients. Desvenlafaxine was associated with small but statistically significant mean changes in laboratory assessments, particularly lipid and liver enzyme elevations, and electrocardiograms; few cases of these changes were clinically relevant.
Desvenlafaxine in the treatment of major depressive disorder exhibited a safety and tolerability profile generally consistent with the serotonin-norepinephrine reuptake inhibitor class. The most common adverse event was transient nausea. At the recommended therapeutic dose of 50 mg/day, discontinuation due to adverse events was similar to placebo.
抗抑郁药的安全性和耐受性特征常常会影响治疗重度抑郁症的临床医生的治疗选择。本研究的目的是描述去甲文拉法辛（以琥珀酸去甲文拉法辛形式给药）治疗抑郁症的安全性和耐受性。
对所有针对重度抑郁症的短期、随机、双盲、安慰剂对照注册研究（四项灵活剂量研究和五项固定剂量研究）进行综合分析。患有重度抑郁症的成年门诊患者接受8周的去甲文拉法辛治疗，剂量范围为50 - 400毫克/天，或接受安慰剂治疗。评估治疗中出现的不良事件、实验室检查值、生命体征和停药症状。在固定剂量研究子集中，分析剂量相关效应。
在总体人群中（安慰剂组：n = 1116；去甲文拉法辛组：n = 1834），不良事件导致3%的安慰剂治疗患者和12%的去甲文拉法辛治疗患者停药；在固定剂量研究子集中，安慰剂组的停药率为4%，而去甲文拉法辛组的停药率随剂量增加（50毫克/天：4%；400毫克/天：18%）。最常见的治疗中出现的不良事件是短暂性恶心，通常为轻度至中度。与去甲文拉法辛治疗相关的最常见性功能障碍是男性勃起功能障碍（7%，而安慰剂组为1%）和女性性高潮障碍（1%和0%）。一名接受去甲文拉法辛治疗的患者死于自杀；在治疗期间有四次自杀未遂（三次去甲文拉法辛组，一次安慰剂组）和八例自杀意念（五次去甲文拉法辛组，三次安慰剂组）。所有去甲文拉法辛剂量均出现平均血压的微小但具有统计学意义的变化；在1%的安慰剂治疗患者和2%的去甲文拉法辛治疗患者中观察到具有临床意义的变化。去甲文拉法辛与实验室评估中的微小但具有统计学意义的平均变化相关，特别是脂质和肝酶升高以及心电图变化；这些变化中很少有临床相关性。
去甲文拉法辛治疗重度抑郁症的安全性和耐受性特征总体上与5-羟色胺-去甲肾上腺素再摄取抑制剂类一致。最常见的不良事件是短暂性恶心。在推荐治疗剂量50毫克/天时，因不良事件停药的情况与安慰剂相似。
