前沿第三十三期:乳腺癌伴抑郁:药物治疗 VS 心理治疗

2018-01-10 08:00 来源:《前沿》杂志 作者:戴南 许秀峰
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乳腺癌患者抑郁障碍患病率高

乳腺癌是女性最常见的恶性肿瘤,据统计 2008 年全世界新增乳腺癌病例 138 万人,占当年所有癌症发病的 23% [1]

近年,乳腺癌患者五年生存率不断提高,目前可达到 89%[2] 。随着预后的改善,乳腺癌患者的情绪问题得到越来越多关注,约 10%~25% 的乳腺癌患者受抑郁障碍困扰 [3]。但不同研究中乳腺癌伴抑郁障碍的患病率差异较大(1%~56%)[4],其中,亚洲人群患病率约为 12.5%~31%[5-7]

各研究中筛查及诊断工具的不同是造成结果差异的主要原因 [4]。另外,乳腺癌患者的年龄、经济状态及治疗方式等不同也对抑郁患病率有所影响 [8]

心理因素是发病主因

乳腺癌患者在面对乳腺癌诊断时,在之后的手术、放疗及化疗过程中都将经历各种心理应激 [9];这些心理应激(包括形体的改变、复发的风险等)可能是乳腺癌患者抑郁障碍发病率较高的主要原因 [3]

另外,乳腺癌患者雌激素的减少和促炎性细胞因子水平的增加也可能增加了乳腺癌患者抑郁障碍的发病率 [10, 11]

治疗可获益,但尚缺乏指南

许多研究表明,乳腺癌患者共病抑郁障碍会影响患者生活质量 [3, 12],降低治疗依从性 [3],并增加家庭及照料者负担 [3]。早期诊断和治疗乳腺癌患者抑郁症状,不但能改善患者生活质量,还可增加患者生存率 [3]

目前,药物治疗、心理治疗以及联合使用药物和心理治疗已被用于改善乳腺癌患者的抑郁障碍 [3]。但由于缺乏专门针对乳腺癌患者抑郁障碍的治疗指南,乳腺癌患者抑郁障碍的药物治疗仍采用与抑郁障碍治疗相同的原则。

已有少量 RCT 研究证明药物治疗的有效性

SSRI 和 SNRI 仍为临床中改善乳腺癌患者抑郁障碍最常用的药物。已有研究报道,SSRI 和 SNRI 可改善乳腺癌患者的抑郁及更年期症状 [13-15],但这些研究的样本量都较少 [3],且结论尚存有一定争议 [3, 16]

与安慰剂对照相比较的随机对照研究能够为乳腺癌患者抑郁障碍的治疗提供更有力的证据和指导,但目前这类研究还较少。根据 Carvalho 等的综述研究,截至 2013 年,乳腺癌患者中运用抗抑郁剂治疗抑郁障碍的 RCT 研究仅有 2 篇 [17]

一篇研究报道帕罗西汀(20 mg/天)可以改善乳腺癌患者的抑郁症状 [18];另一篇研究舍曲林(50 mg/天)在使用他莫昔芬的乳腺癌患者中的抗抑郁作用及有效性 [13],研究发现,与对照组相比,舍曲林可在一定程度上改善患者躯体症状。而一项系统综述对既往 5 项研究的汇总分析发现,文拉法辛可显著改善乳腺癌患者的潮热症状 [19],且使用剂量明显小于治疗典型抑郁症时的剂量 [20]

另外,有小样本 RCT 双盲研究显示,在乳腺癌术后患者中使用褪黑素可有效预防抑郁障碍的发生,腿黑素组 vs 安慰剂对照组 = 11%(3/27)vs 45%(9/20),RR 0.25(95%CI 0.077~0.80)[21]

抗抑郁药与抗肿瘤药的相互作用值得关注

由于部分抗抑郁药物与抗肿瘤药物之间存在相互作用,目前乳腺癌患者抗抑郁药物的选择也需要关注。

他莫昔芬可降低雌激素水平,是目前治疗乳腺癌的主要药物之一。肝脏细胞色素 P450 中 2D6 能将体内的他莫昔芬代谢为活性产物(endoxifen)[22],而部分 SSRI 及 SNRI 都会抑制 CYP 2D6(如氟西汀、帕罗西汀)。因此使用抗抑郁剂可能会抑制 CYP 2D6 而影响他莫昔芬的活性,从而影响乳腺癌的治疗 [23]

2010 年的一项研究探讨在他莫昔芬的乳腺癌患者中使用不同 SSRI 药物和文拉法辛的疗效,结果发现他莫昔芬和帕罗西汀的联合使用会导致乳腺癌患者更高的死亡率 [24]

最新 RCT 研究证明心理干预有效

一项多中心 RCT 研究(n = 157)结果显示,短程精神动力疗法(short-term psychodynamic psychotherapy, STPP)与常规治疗相比,不仅可显著提高乳腺癌伴抑郁障碍患者的缓解率,改善生命质量 [25],还有助于改善疲乏症状 [26]

另有 RCT 研究(n = 240)探讨了认知行为压力管理(cognitive-behavioral stress management, CBSM)对非转移乳腺癌伴抑郁障碍患者干预的长期效果;患者在进行 10 周 CBSM 干预后随访 5 年,结果发现 5 年后 CBSM 组抑郁症状仍明显低于对照组 [27]。这预示患者经 CBSM 干预后效果得到了长期维持。

还有一项 RCT 研究(n = 170)发现,每天 2 次「音乐疗法+渐进式肌肉放松训练」不仅可改善乳腺癌术后患者抑郁和焦虑症状,还可有效缩短住院时间 [28]


参考文献

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编辑: 孔宇森

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