Institute of General Practice, |Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590, Frankfurt, Germany.
Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia.
Syst Rev. 2020 Mar 17;9(1):59. doi: 10.1186/s13643-020-01296-8.
Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-the-counter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals.
A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including < 100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using meta-regression (for indication, outcome, and time points) and I statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment.
We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations.
Submitted to PROSPERO; assignment is in progress.
人们低估了抗胆碱能作用的不良影响，并且经常忽视它。如果不能识别药物不良反应（ADR），可能会导致处方连锁反应，并导致不必要地使用非处方产品。本系统评价和荟萃分析的目的是探索和量化与阿米替林相比，安慰剂在涉及任何适应症的成人和健康个体的随机对照试验（RCT）中引起的 ADR 的频率和严重程度。
将在六个电子数据库中进行系统搜索、向前/向后搜索、手动搜索以及食品和药物管理局（FDA）和欧洲药品管理局（EMA）批准研究的搜索。将纳入评估任何剂量阿米替林的安慰剂对照 RCT，无论适应症如何，且不限制发表时间和语言，也将纳入健康个体。将排除局部阿米替林、联合治疗或纳入<100 名参与者的研究。两名研究者将独立筛选研究、评估方法学质量，并提取关于设计、人群、干预和结局的信息（非抗胆碱能 ADR，例如症状、测试结果和不良药物事件（ADE），如跌倒）。主要结局将是非抗胆碱能 ADR 的频率作为二项结局（阿米替林组与安慰剂组中出现/未出现抗胆碱能 ADR 的绝对患者数）。抗胆碱能 ADR 将由一位经验丰富的临床药理学家根据文献和 Martindale：完整药物参考中的数据进行定义。次要结局将是（非）抗胆碱能 ADR 和 ADE 的频率和严重程度。信息将通过荟萃分析和叙述进行综合。我们打算使用 meta 回归（针对适应症、结局和时间点）和 I 统计来评估异质性。二项结局将表示为优势比，连续结局将表示为标准化均数差。将使用 95%置信区间提供效应量。我们计划进行敏感性分析，以评估方法学质量、结局报告等，并进行年龄、剂量和治疗持续时间的亚组分析。
通过比较阿米替林与安慰剂的发生率，我们将定量评估任何适应症下服用阿米替林的成年人的抗胆碱能和其他 ADR/ADE 的频率，从而防止疾病症状和反安慰剂效应带来的偏倚。由于没有标准化的工具来衡量它，我们对抗胆碱能 ADR 的总体估计可能存在局限性。
已提交给 PROSPERO；正在分配中。
