Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Clin Trials. 2023 Dec;20(6):632-641. doi: 10.1177/17407745231182010. Epub 2023 Jun 22.
Chronic pain and depression are common comorbid conditions, but there is limited evidence-based guidance for management of the two conditions together. In recent years, there has been an increase in the number of chronic pain randomized controlled trials that collect depression outcomes, but it is unknown how often these trials include people with depression or significant depressive symptoms. If trials do not include participants representative of real-world populations, evidence and guidance generated from these trials risk being inapplicable for large proportions of the target population, or worse, risk harm. Thus, in order to identify pathways to improve the conduct of clinical trials, the aims of this study were to (1) estimate the proportion of randomized controlled trials evaluating chronic pain interventions and reporting depression outcomes that include participants with significant depressive symptoms; and (2) assess the variability of inclusion proportions by pain type, intervention type, gender, country of origin, and publication year.
Studies were extracted from an umbrella review of interventions for chronic pain that reported depression outcomes. Screening and data extraction were completed in duplicate and conflicts were resolved by a third author. Randomized controlled trials with at least 50% adult participants and validated depression scales were included, and randomized controlled trials with populations whose mean scores were at or above depression thresholds at baseline were considered to have included participants with depression.
Of the 346 randomized controlled trials analyzed, 142 (41%) included participants with depression. Eight pain-type groups and nine intervention types were identified. Randomized controlled trials investigating fibromyalgia and mixed chronic pain had the highest proportion of participants with depression, whereas studies of arthritis and axial pain had among the lowest. Randomized controlled trials from the United States had a significantly lower inclusion proportion compared with non-US studies, especially for studies on arthritis. The increase in inclusion proportion by publication year was driven by the increase in fibromyalgia studies.
This study highlights opportunities to improve the conduct of chronic pain clinical trials. The majority of randomized controlled trials s analyzed evaluated participants without significant depressive symptoms at baseline, thus the findings synthesized in systematic reviews and subsequent guidelines are most applicable to the subset of real-world populations that do not have significant depressive symptoms. As well, systemic biases around psychological conditions and gender may be important contributors to differences in the study of depression in fibromyalgia compared with common conditions such as arthritis and axial pain. In order to better inform clinical practice, future research must intentionally include individuals with comorbid depression in trials of common chronic pain conditions, and consider methods to mitigate biases that may distort study design.
慢性疼痛和抑郁症是常见的共病，但针对这两种疾病的联合管理，目前仅有有限的循证医学指导。近年来，评估慢性疼痛的随机对照试验（RCT）数量有所增加，这些试验均收集了抑郁结局，但尚不清楚这些试验中纳入了多少患有抑郁症或显著抑郁症状的患者。如果试验纳入的患者不具有代表性，那么这些试验产生的证据和指导就可能不适用于大部分目标人群，甚至可能会带来危害。因此，为了明确改善临床试验实施的途径，本研究旨在：（1）评估评估慢性疼痛干预措施并报告抑郁结局的 RCT 中，纳入患有显著抑郁症状患者的比例；（2）评估按疼痛类型、干预类型、性别、国家来源和发表年份划分的纳入比例的变异性。
研究从针对慢性疼痛的干预措施的伞式综述中提取数据，该综述报告了抑郁结局。筛查和数据提取均由两名作者进行，对存在分歧的内容由第三名作者裁决。纳入至少 50%的成年参与者且使用了经过验证的抑郁量表的 RCT ，以及基线时平均得分达到或高于抑郁阈值的人群的 RCT 被认为纳入了患有抑郁症的患者。
在分析的 346 项 RCT 中，有 142 项（41%）纳入了患有抑郁症的患者。共确定了 8 种疼痛类型组和 9 种干预类型。研究纤维肌痛和混合性慢性疼痛的 RCT 纳入抑郁症患者的比例最高，而研究关节炎和轴性疼痛的 RCT 纳入抑郁症患者的比例最低。与非美国研究相比，美国的 RCT 纳入比例显著较低，尤其是关节炎相关研究。发表年份的纳入比例增加是由纤维肌痛研究的增加驱动的。
本研究强调了改善慢性疼痛临床试验实施的机会。分析中大多数 RCT 评估的参与者在基线时没有显著的抑郁症状，因此系统评价和随后的指南综合的结果最适用于没有显著抑郁症状的现实世界人群。此外，在纤维肌痛与关节炎和轴性疼痛等常见疾病的抑郁研究中，心理状况和性别方面的系统性偏见可能是造成差异的重要原因。为了更好地为临床实践提供信息，未来的研究必须有意在常见慢性疼痛疾病的试验中纳入患有共病性抑郁症的个体，并考虑采用方法减轻可能扭曲研究设计的偏见。
