Stein D J, Zungu-Dirwayi N, Seedat S
University of Stellenboseh, Tygerberg 7505, South Africa.
Cochrane Database Syst Rev. 2000(4):CD002795. doi: 10.1002/14651858.CD002795.
Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. By definition prior psychological trauma plays a causal role in the disorder, and psychotherapy is a widely accepted intervention. Nevertheless there is growing evidence that PTSD is characterized by specific psychobiological dysfunctions, and this has contributed to a growing interest in the use of medication in its treatment.
The authors aimed to undertake a systematic review of randomized controlled trials (RCTs) of the pharmacotherapy of posttraumatic stress disorder (PTSD) following the guidelines and using the software of the Cochrane Collaboration, and to provide an estimate of the effects of medication in this disorder. Secondary objectives were to explore questions about whether particular classes of medication are more effective and/or acceptable than others in the treatment of PTSD, and about which factors (clinical and methodological) predict response to pharmacotherapy.
Studies of the pharmacotherapy of PTSD were identified using literature searches of MEDLINE (1966 to 1999, using the textwords posttraumatic, post-traumatic, medication, pharmacotherapy) and other electronic databases (PSYCLIT; National PTSD Center Pilots database; Dissertation Abstracts; Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register). In addition, published and unpublished RCTs were requested from PTSD researchers and pharmaceutical companies. An initial broad strategy was undertaken to find not only RCTs, but also open-label trials and reviews of the pharmacotherapy of PTSD; additional studies were sought in reference lists of retrieved articles and included studies in any language.
All RCTs of PTSD (including both placebo controlled and comparative trials), whether published or unpublished, but completed prior to the end of 1999 were considered for the review.
Selected RCTs were independently assessed and collated by 2 raters, and Review Manager (RevMan) software was used to capture data on treatment response and PTSD symptom ratings. Ratings of subtypes of PTSD symptoms (intrusive/re-experiencing, avoidant/numbing, hyperarousal), of comorbid symptoms (depression, anxiety), and of quality of life were included where possible. A range of additional information, which may explain possible clinical and methodological heterogeneity amongst the trials, was also captured. Summary statistics for dichotomous and continous measures were calculated, heterogeneity was assessed, and subgroup/sensitivity analyses undertaken.
15 short-term (12 weeks or less) RCTs were found, of which 9 had sufficient data for inclusion in the analysis. Methodological limitations were particularly apparent in early work; these included short (5 weeks or less) duration of trials and a reliance on self-report scales (rather than use of standardized clinician-rated scales). Despite these and other potentially important differences between the trials, many trials demonstrated efficacy for medication over placebo. Summary statistics were calculated for the Clinical Global Impressions scale change item (CGI-C) or close equivalent from 10 sets of data including various antidepressants and other agents - the proportion of non-responders was lower in the pharmacotherapy group than in the control group (relative risk (95% CI) = 0.72 (0.64, 0.83)). Similarly, summary statistics for the intrusion, avoidance and total scales of the Impact of Events Scale (IES) from 4sets of data again including various agents showed a statistically (and clinically) significant difference between medication and placebo (Weighted Mean Difference (95% CI) = -3.81 (-6.72,-0.91), -3.31(-5.24,-1.37), -7.18 (-11.86,-2.50) respectively).
REVIEWER'S CONCLUSIONS: Medication treatments can be effective in PTSD, acting to reduce its core symptoms, and should be considered as part of the treatment of this disorder. The existing evidence base does not provide sufficient data to suggest particular predictors of response to treatment, or to demonstrate that any particular class of medication is more effective or better tolerated than any other. However, the largest trials showing efficacy to date have been with the SSRIs, and in contrast, there have been negative studies of some agents. Given the high prevalence and enormous personal and societal costs of PTSD, there is a need for additional controlled trials in this area. Additional questions for future research include the effects of medication on quality of life in PTSD, appropriate dose and duration of medication, the use of medication in different trauma groups, in pediatric and geriatric subjects, and the value of early (prophylactic), combined (with psychotherapy), and long-term (maintenance) medication treatment.
创伤后应激障碍（PTSD）是一种常见且致残的疾病。根据定义，先前的心理创伤在该疾病中起因果作用，心理治疗是一种被广泛接受的干预措施。然而，越来越多的证据表明，PTSD具有特定的心理生物学功能障碍，这使得人们对药物治疗该疾病的兴趣日益增加。
作者旨在按照Cochrane协作网的指南并使用其软件，对创伤后应激障碍（PTSD）药物治疗的随机对照试验（RCT）进行系统评价，并评估药物治疗该疾病的效果。次要目的是探讨特定类别的药物在治疗PTSD方面是否比其他药物更有效和/或更可接受，以及哪些因素（临床和方法学）可预测药物治疗的反应。
通过检索MEDLINE（1966年至1999年，使用关键词“创伤后”“创伤后应激障碍”“药物治疗”“药物疗法”）以及其他电子数据库（PSYCLIT；国家PTSD中心试点数据库；论文摘要；Cochrane协作网抑郁、焦虑与神经症对照试验注册库）来识别PTSD药物治疗的研究。此外，还向PTSD研究人员和制药公司索取已发表和未发表的RCT。最初采用广泛的检索策略，不仅要找到RCT，还要找到开放标签试验和PTSD药物治疗的综述；在检索到的文章的参考文献列表中寻找其他研究，并纳入任何语言的研究。
本综述考虑了所有已发表或未发表的PTSD的RCT（包括安慰剂对照试验和比较试验），但试验需在1999年底之前完成。
由2名评价员独立评估和整理所选的RCT，并使用Review Manager（RevMan）软件收集治疗反应和PTSD症状评分的数据。尽可能纳入PTSD症状亚型（侵入性/重新体验、回避/麻木、过度警觉）、共病症状（抑郁、焦虑）以及生活质量的评分。还收集了一系列可能解释试验中临床和方法学异质性的其他信息。计算二分法和连续测量的汇总统计量，评估异质性，并进行亚组/敏感性分析。
共找到15项短期（12周或更短）RCT，其中9项有足够的数据纳入分析。方法学局限性在早期研究中尤为明显；这些局限性包括试验持续时间短（5周或更短）以及依赖自我报告量表（而非使用标准化的临床医生评定量表）。尽管试验之间存在这些以及其他潜在的重要差异，但许多试验表明药物治疗比安慰剂更有效。计算了临床总体印象量表变化项（CGI-C）或来自10组数据（包括各种抗抑郁药和其他药物）的相近指标的汇总统计量——药物治疗组中无反应者的比例低于对照组（相对危险度（95%CI）=0.72（0.64，0.83））。同样，来自4组数据（同样包括各种药物）的事件影响量表（IES）的侵入、回避和总分量表分项的汇总统计量显示，药物治疗与安慰剂之间在统计学上（以及临床上）存在显著差异（加权均数差（95%CI）分别为=-3.81（-6.72，-0.91），-3.31（-5.24,-1.37），-7.18（-11.86，-2.50））。
药物治疗对PTSD有效，可减轻其核心症状，应被视为该疾病治疗的一部分。现有的证据基础没有提供足够的数据来表明治疗反应的特定预测因素，或证明任何特定类别的药物比其他药物更有效或耐受性更好。然而，迄今为止显示有效的最大规模试验是使用选择性5-羟色胺再摄取抑制剂（SSRI）进行的，相比之下，对某些药物的研究结果为阴性。鉴于PTSD的高患病率以及巨大的个人和社会成本，该领域需要更多的对照试验。未来研究的其他问题包括药物对PTSD患者生活质量的影响、药物的合适剂量和疗程、不同创伤群体中药物的使用、儿科和老年患者中药物的使用，以及早期（预防性）、联合（与心理治疗）和长期（维持性）药物治疗的价值。
