Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Mult Scler Relat Disord. 2018 Nov;26:124-156. doi: 10.1016/j.msard.2018.09.008. Epub 2018 Sep 12.
Psychiatric comorbidity is prevalent in persons with multiple sclerosis (MS). Few studies have assessed whether second-generation disease-modifying therapies (DMT) are associated with adverse psychiatric effects.
We aimed to systematically review the literature regarding the APEs associated with natalizumab, fingolimod, dimethyl fumarate, teriflunomide and alemtuzumab in MS. As a secondary objective, we evaluated changes in anxiety or depression scores following treatment with the aforementioned DMTs.
We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts, PsychINFO, Central Register of Controlled Trials & Cochrane database of systematic reviews for published studies, and clinicaltrials.gov and regulatory documents from the US and Canada for unpublished studies. Data sources were searched from inception to September 2017. Studies reporting adverse psychiatric effects involving any DMT of interest were included. We report the incidence proportions of the adverse psychiatric effects and, where applicable, risk differences between DMT-exposed and unexposed individuals along with the corresponding 95% confidence intervals. We calculated the standardized mean differences (SMD) of changes in anxiety and depression scores if reported as study outcomes, and pooled the data using random effects meta-analysis.
Of 4389 abstracts screened, 78 met the inclusion criteria, including 48 clinical trials, 28 observational studies and 2 case reports. Depression was the most commonly reported adverse psychiatric effect. Incidence proportions for all adverse psychiatric effects ranged from 0 to 24.7%. None of the DMT studied were associated with a statistically significant increased risk of any adverse psychiatric effect (range of risk difference: -7.69% [95%CI: -16.06%, 5.56%] to 6.67 [-8.56, 15.59]). Eighteen studies examined changes in depression or anxiety following fingolimod, natalizumab or dimethyl fumarate treatment; depression symptoms improved in fingolimod-treated groups (SMD [95%CI]: 1.18 [0.17, 2.19]). We did not identify studies examining changes in these outcomes following treatment with any of the other DMTs.
The DMTs reviewed were not associated with an increased risk of adverse psychiatric effect in MS, and some may reduce the incidence of depressive symptoms. This may reflect either a positive direct effect (e.g. immune modulation) or an indirect effect arising due to a positive impact on disease activity or course.
精神共病在多发性硬化症（MS）患者中很常见。很少有研究评估第二代疾病修正疗法（DMT）是否与不良精神影响有关。
我们旨在系统地回顾与 MS 中那他珠单抗、芬戈莫德、二甲基富马酸、特立氟胺和阿仑单抗相关的不良精神影响的文献。作为次要目标，我们评估了使用上述 DMT 治疗后焦虑或抑郁评分的变化。
我们检索了 MEDLINE、EMBASE、国际药学文摘、心理信息、对照试验注册中心和 Cochrane 系统评价数据库，以获取已发表的研究，以及临床试验.gov 和美国和加拿大的监管文件，以获取未发表的研究。数据来源从开始检索到 2017 年 9 月。纳入了报告任何感兴趣的 DMT 相关不良精神影响的研究。我们报告了不良精神影响的发生率，并在适用的情况下，报告了 DMT 暴露和未暴露个体之间的风险差异以及相应的 95%置信区间。如果作为研究结果报告了焦虑和抑郁评分的变化，则我们计算了标准化均数差（SMD），并使用随机效应荟萃分析汇总数据。
在筛选的 4389 篇摘要中，有 78 篇符合纳入标准，包括 48 项临床试验、28 项观察性研究和 2 项病例报告。抑郁是最常见的不良精神影响。所有不良精神影响的发生率范围为 0 至 24.7%。没有一种研究的 DMT 与任何不良精神影响的风险增加具有统计学显著相关性（风险差异范围：-7.69%[95%CI：-16.06%，5.56%]至 6.67%[-8.56%，15.59%]）。有 18 项研究检查了 fingolimod、那他珠单抗或二甲基富马酸治疗后抑郁或焦虑的变化；fingolimod 治疗组的抑郁症状改善（SMD[95%CI]：1.18[0.17，2.19]）。我们没有发现研究检查任何其他 DMT 治疗后这些结果的变化。
所审查的 DMT 与 MS 中的不良精神影响风险增加无关，并且某些 DMT 可能会降低抑郁症状的发生率。这可能反映了直接的积极影响（例如免疫调节），或者由于对疾病活动或病程的积极影响而产生的间接影响。
