基于大麻的药物治疗疼痛的疗效:随机对照试验的系统评价和荟萃分析。
Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
机构信息
Faculty of Social Welfare and Health Sciences, University of Haifa, Israel and Rambam Health Care Campus, Haifa, Israel.
The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
出版信息
Pain Physician. 2017 Sep;20(6):E755-E796.
BACKGROUND
The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field.
OBJECTIVES
This study's aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians' and researchers' knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment.
STUDY DESIGN
A systematic review and meta-analysis.
METHODS
An electronic search was conducted using Medline/Pubmed and Google Scholar with the use of Medical Subject Heading (MeSH) terms on all literature published up to July 2015. A follow-up manual search was conducted and included a complete cross-check of the relevant studies. The included studies were RCTs which compared the analgesic effects of CBMs to placebo. Hedges's g scores were calculated for each of the studies. A study quality assessment was performed utilizing the Jadad scale. A meta-analysis was performed utilizing random-effects models and heterogeneity between studies was statistically computed using I² statistic and tau² test.
RESULTS
The results of 43 RCTs (a total of 2,437 patients) were included in this review, of which 24 RCTs (a total of 1,334 patients) were eligible for meta-analysis. This analysis showed limited evidence showing more pain reduction in chronic pain -0.61 (-0.78 to -0.43, P < 0.0001), especially by inhalation -0.93 (-1.51 to -0.35, P = 0.001) compared to placebo. Moreover, even though this review consisted of some RCTs that showed a clinically significant improvement with a decrease of pain scores of 2 points or more, 30% or 50% or more, the majority of the studies did not show an effect. Consequently, although the primary analysis showed that the results were favorable to CBMs over placebo, the clinical significance of these findings is uncertain. The most prominent AEs were related to the central nervous and the gastrointestinal (GI) systems.
LIMITATIONS
Publication limitation could have been present due to the inclusion of English-only published studies. Additionally, the included studies were extremely heterogeneous. Only 7 studies reported on the patients' history of prior consumption of CBMs. Furthermore, since cannabinoids are surrounded by considerable controversy in the media and society, cannabinoids have marked effects, so that inadequate blinding of the placebo could constitute an important source of limitation in these types of studies.
CONCLUSIONS
The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.Key words: Cannabis, CBMs, chronic pain, postoperative pain, review, meta-analysis.
背景
慢性疼痛的管理是全球范围内的一个复杂挑战。基于大麻的药物(CBMs)已被证明在减轻慢性疼痛方面非常有效,尽管该主题在该领域仍然存在很大争议。
目的
本研究旨在进行一项结论性的综述和荟萃分析,其中包括所有随机对照试验(RCTs),以更新临床医生和研究人员对 CBMs 治疗慢性和术后疼痛的疗效和不良事件(AEs)的认识。
研究设计
系统评价和荟萃分析。
方法
使用 Medline/Pubmed 和 Google Scholar 进行电子检索,并使用 Medical Subject Heading(MeSH)术语对截至 2015 年 7 月发表的所有文献进行检索。进行了后续的手动搜索,并包括对相关研究的全面交叉检查。纳入的研究是比较 CBMs 与安慰剂镇痛效果的 RCTs。为每项研究计算了 Hedges 的 g 分数。使用 Jadad 量表进行研究质量评估。使用随机效应模型进行荟萃分析,并使用 I²统计量和 tau²检验统计计算研究之间的异质性。
结果
本综述共纳入 43 项 RCTs(共 2437 名患者),其中 24 项 RCTs(共 1334 名患者)符合荟萃分析的条件。这项分析表明,慢性疼痛中疼痛减轻的证据有限-0.61(-0.78 至-0.43,P<0.0001),特别是通过吸入-0.93(-1.51 至-0.35,P=0.001)与安慰剂相比。此外,尽管本综述包括一些 RCTs 显示疼痛评分降低 2 分或更多,即 30%或 50%或更多,具有临床意义的改善,但大多数研究并未显示出效果。因此,尽管主要分析表明 CBMs 相对于安慰剂的结果有利,但这些发现的临床意义尚不确定。最突出的不良事件与中枢神经系统和胃肠道(GI)系统有关。
局限性
由于纳入了仅发表英文的研究,因此可能存在发表偏倚。此外,纳入的研究非常异质。只有 7 项研究报告了患者先前使用 CBMs 的病史。此外,由于大麻素在媒体和社会中存在相当大的争议,大麻素具有显著的作用,因此安慰剂的盲目性不足可能是这些类型研究的一个重要限制来源。
结论
基于有限的证据,本系统综述表明 CBMs 可能对慢性疼痛治疗有效,主要适用于神经病理性疼痛(NP)患者。此外,通过口服/口腔途径给予 CBMs 比通过吸入途径更常发生胃肠道不良事件。
关键词
大麻,CBMs,慢性疼痛,术后疼痛,综述,荟萃分析。