第五章 药物中心观的临床意义 (2)
抗抑郁药
被认为可以缓解抑郁症状的药物已经使用了好几十年。20世纪70年代至80年代，随着三环类抗抑郁药的引入，它们的使用量增加，然后在20世纪90年代及以后，随着选择性5-羟色胺再摄取抑制剂的引入，它们的使用量激增[3,24]。除了抑郁症，他们的适应症也扩大到包括焦虑症、疼痛、强迫症、创伤后应激障碍和暴食症。所有这些都使这些药物的目标人群越来越多。现在，九分之一的美国人服用抗抑郁药（而三十年前这一比例仅为五十分之一），其中25%的人已经服用了十年或更长时间[25]。
然而人们对这些药物的短期的疗效和长期的不良反应感到严重关切。虽然在一些综述中，抗抑郁药物比安慰剂更有效，其影响在统计学上是显著的，但不一定具有临床意义[26]。也就是说，有足够大的样本量来检测临床评分量表上活性药物和安慰剂之间的微小差异，但这些差异不太可能对个体的幸福感产生太大影响[27]。长期使用的建议基于复发数据；然而，与抗精神障碍药物的发现类似，这些药物也可能对长期结局产生恶化作用。Vittengyl[28]评估了抑郁症亲历者的连续9年的跟踪结果，发现接受抗抑郁药药物治疗的人比未接受抗抑郁药物治疗的人的情况更糟。为了检验这个有竞争力的假设，即由于那些服用药物的人有更严重的抑郁症状，他使用了一个全国性的个体样本，包括症状严重程度和社会经济状况的评估，以及治疗剂量。他发现，即使在控制了严重症状后，进行药物治疗仍然会产生负面影响。
其他研究也表明:随着时间的推移，继续服药的个体比停止服药或从未服用过抗抑郁药的个体表现更差。这些发现似乎不能用治疗状况严重程度的差异来解释。研究人员在世界卫生组织关于抑郁症筛查工具功效的一项研究中发现，通过筛查确定患有抑郁症并接受抗抑郁药物治疗的人比那些被诊断患有抑郁症但没有给予指定药物治疗的人表现更差[29]。两组的基线严重程度评分相同。如果一个人对药物有反应，但停药后又复发，那么重新开始用药似乎是显而易见的做法。然而，Posternal及其同事[30]研究了84名最初对抗抑郁药物有反应但停药后复发的患者，他们没有恢复药物治疗，但在1年时间，85%的人的抑郁症状得到缓解。
氟西汀上市后不久就有报告称，该药物可能与某些个体内产生的强烈的自杀或攻击感的发作有关[31]。人们特别关注在儿童和青少年中会出现这种风险[32]。然而，一些专家认为风险是很小的，自杀事件被归因于药物治疗之外的精神状态。有些精神科医生对这些药物的潜在危害提出警告,但人们却批评他们在吓唬人,让人们不敢服药。即便FDA在发布关于自杀风险的“黑框警告”后，也似乎仅仅在之后的几年内影响了处方的开具[33]。此外，没有强有力的证据表明SSRI处方率与自杀率降低之间存在关联[34]。幸运的是，自杀是一种极小概率的事件，而且两者之间的关联也不能证明因果关系。专家们经常争论各种统计分析的相对优点。然而，当人们的处方中出现这些药物时，没有理由不将这种担忧纳入知情同意程序。
短期疗效的适当证据,结合目前存在的许多关于短期副作用和长期不良后果的问题，支持谨慎使用抗抑郁药物。
苯二氮卓类
尽管从以药物为中心的视角来看，精神科医生可能更难考虑镇静剂，但它比苯二氮卓类药的挑战可能要小。苯二氮卓类药是有多种适应症的老药。它们被认为会引起依赖成瘾和戒断症状。任何服用它们的人都能明显地看到它们的短期益处，而且对患有特定综合症或精神障碍的人来说没有特异性；它们对每个人都有镇静作用，即便不能立即诱导入睡，大多数人也都会体验到镇静之类的效果。尽管在某些情况下，不同的苯二氮卓化合物在不同的条件下使用，但这些差异完全是由于不同的药代动力学，即不同的吸收率、临床作用的开始和抵消以及清除率导致的。例如，一种被迅速吸收和清除的药物作为睡眠辅助会更好，而一种吸收速度较慢、清除半衰期较长的药物对持续焦虑的人更有帮助。
以疾病为中心的范式与我们对苯二氮卓类药物的理解相关，因为它对我们涉及这些药物的知识产生了影响。与其他药物类似，最初的研究侧重于在短期研究中确定特定适应症的疗效，对长期结果的评估有限。人们早就认识到会出现药物上瘾和被滥用的情形，而且近年来越来越多的证据表明，使用这些药物与总体死亡率的增加相关[35]。Lembke及其同事报告说，从1999年到2015年，美国由于苯二氮卓类药物使用过量的死亡人数增加了近九倍[36]。长期接触苯二氮卓类药物与记忆损害风险的增加相关[37]。它们与跌倒、抑郁、感染、癌症、自杀和总体死亡率的风险增加有关[35]。然而，尽管如此，它们仍然是常见的处方。在美国，从1996年到2013年，被开具苯二氮卓类药物处方的成年人的数量增加了67%[36]。
结论
如果要比较以药物为中心与以疾病为中心的药物治疗模式的内涵，可以针对许多种类的精神活性药物来进行验证。主题是相似的：短期疗效和停药后复发风险增加，再加上将精神障碍理解（概念化）为慢性病，引导病建议就诊者长期用药。与复发有别的关于戒断反应的考虑通常被忽略，因为有数据表明许多人在没有药物治疗的情况下康复。尽管对药物特异性的概念有着持续的关注，但每一类药物似乎都有着不断扩大的适应症。这导致越来越多的人在无限期内服用越来越多的药物。随着时间的推移，出现的证据表明，继续服用这些药物的人似乎比停止服用这些药物的人表现更差。
这就提出了有关影响医生开处方的因素的有意思的话题。首先，理解安慰剂反应的概念很重要。大多数人认为这是期望的结果的表现；人们期望发生的事情更有可能发生。将短期结果数据解释为药物无效是不正确的。另一方面，这场争论与服用安慰剂和服用活性药物的就诊者的反应是否存在显著差异有关。
在临床实践中,我们经常面临这样的困境：尽管许多人报告对药物治疗有良好的反应，但我们仍无法知道在每种情况下，这种改善在多大程度上代表了安慰剂反应，而不是我们所开药物的特定药理学特性所带来的益处。让我们考虑一个困扰者服用药物后的临床情况，他感觉好一点，对药物没有产生任何严重的副作用，但是，基于对长期不良后果的潜在风险的考虑，正在考虑是否继续服药下去是有意义的。如果停药，患者可能会经历两种可能的短期结果：没有变化或感觉更糟。
了解以药物为中心的治疗模式的医生和就诊者可能能够度过感觉更糟的时期，因为他们知道这可能会过去,而且，随着时间的推移，通过耐受这段困难时期可能会有更多的好处。医生倾向于恢复用药——或者压根不尝试停止用药——这可能是因为影响临床决策的认知偏见导致的。
发现结果具有不确定性时,丹尼尔·卡尼曼和其他认知心理学家研究了影响决策的各种偏见。在他的书《思考，快与慢》（Thinking，Fast and Slow）[38]中，他描述了影响决策的常见启发或“经验法则”。尽管医生们相信自己是在遵循循证指南的理性规则下行事，但各种偏见仍然影响着每个人，甚至是那些在各自专业领域受过良好教育的专家也避免不了。一个强大的偏见是关于对损失的厌恶，被“更强烈地驱使去避免损失而不是获得收益”（第302页）。另一个影响是可能性启发，人们更会受到易回忆事件的影响。
对于就诊者和医生来说，症状的“复发”或恶化将是一种负面结果——一种损失。本章讨论的与长期接触药物相关的风险更为遥远一些。因此，相较于短期和更直接的复发风险，它们对医生决策过程的影响要小。这些偏见有助于医生——以及许多就诊者——反对停药。
然而，被称为“以药物为中心”的这种更适当的药物治疗思维模式似乎是有道理的。鉴于我们目前生活在一种精神活性药物被广泛开具和积极推广的文化中，许多人服用的药物可能不仅对他们没有帮助，而且实际上可能对他们有害。此外，精神医学中的复合处方激增，这至少部分归因于以疾病为中心的模式和“共存病”精神障碍概念的推广。
基于以药物为中心的思维模式，可以提出几个常规建议：
1.从仔细讨论精神障碍的诊断开始。重要的是要强调，精神障碍诊断是用来对相同的体验进行分门别类，但它们不包含关于精神障碍的原因或痛苦来源的信息。
2.在开始用药之前，考虑一下非药物的选择，包括观察等待，减少物质的滥用，改善睡眠和饮食。
3.当建议使用某种药物时，解释该药物针对的是特定的症状而不是疾病本身。
4.告知已知的药物反应，以及它们的正作用和副作用，以及个体经验。
5.提供有关安慰剂对人类的强大影响的信息。
6. 当倡议使用药物时，讨论治疗的持续时间以及逐渐减量和停药的计划。
7. 一个人开始用药后，对广泛的精神活性作用保持关注和好奇心。避免只关注症状。
8.如果药物不起作用或出现不良反应，应先考虑减少剂量或停止使用，然后再考虑是否加入其他药物以解决新出现的问题。
9.一次只做一个改变，确定明确的目标症状，并系统地跟踪药物的影响。保持仔细的文档记录，以便判断多长时间后可以进行系统化再评估。电子健康记录需要被设计以用来支持而不是阻碍这个过程。
10. 在就诊者情况稳定后，讨论可能的药物减量方案。
11.即使一个人一度难以停止药物治疗，这并不一定意味着这种治疗需要无限期地继续下去。与困扰者一起努力减少戒断症状是很重要的。此外，根据困扰者的生活状况，可以随着时间的推移重新考虑药物逐渐减量的问题。
通常，人们来找我们时已经被开具了处方药，在许多情况下还不止一种。下一章将讨论如何戒断这些药物。
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