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孟鲁司特与抗抑郁药物联合治疗——对称性分析

Treatment with montelukast and antidepressive medication-a symmetry analysis.

作者信息

Winkel Jane Sterndorff, Damkier Per, Hallas Jesper, Henriksen Daniel Pilsgaard

机构信息

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.

Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

出版信息

Pharmacoepidemiol Drug Saf. 2018 Dec;27(12):1409-1415. doi: 10.1002/pds.4638. Epub 2018 Aug 23.

Abstract

PURPOSE

Leukotriene receptor antagonists are used in asthma and rhinitis treatment. Pharmacovigilance data have suggested an association between montelukast and depression, but the association has not been established in controlled study designs. We described the association between initiation of montelukast and depression, using prescriptions of antidepressants as a surrogate marker, and assessed whether the association was related to the underlying asthma disease.

METHODS

We performed a symmetry analysis, with a study period from January 1, 2000 to December 31, 2016, using 3 nationwide Danish registers. We included all adults, who filled their first prescription of montelukast and antidepressants within an interval of 1 year. In the absence of an association between montelukast and antidepressant use, a symmetrical distribution of prescriptions is expected before and after montelukast initiation (ie, a sequence ratio [r ] of 1.0). We subcategorized the subjects after the severity of underlying asthma disease.

RESULTS

In total, 4450 subjects filled their first prescriptions of both montelukast and antidepressants within a 1-year interval: 2434 redeemed their first prescription of montelukast before antidepressants, and 2016 redeemed the medications in the opposite order (r 1.21 [95% CI 1.14-1.28]). We found r above unity in groups with long-acting asthma treatment, but no increase in antidepressant prescription, when stratifying by the asthma severity.

CONCLUSION

We found a weak association between the use of montelukast and the risk of being prescribed an antidepressant, unlikely to be of clinical relevance. Stratified analyses suggest that this association may relate to asthma, rather than to montelukast.

摘要

目的

白三烯受体拮抗剂用于治疗哮喘和鼻炎。药物警戒数据表明孟鲁司特与抑郁症之间存在关联,但在对照研究设计中尚未证实这种关联。我们以抗抑郁药处方作为替代指标,描述了孟鲁司特起始使用与抑郁症之间的关联,并评估这种关联是否与潜在的哮喘疾病有关。

方法

我们使用丹麦全国范围内的3个登记处进行了一项对称性分析,研究期为2000年1月1日至2016年12月31日。我们纳入了所有在1年内首次开具孟鲁司特和抗抑郁药处方的成年人。如果孟鲁司特与抗抑郁药使用之间不存在关联,那么在孟鲁司特起始使用前后的处方分布应是对称的(即序列比[r]为1.0)。我们根据潜在哮喘疾病的严重程度对受试者进行了亚分类。

结果

共有4450名受试者在1年内首次开具了孟鲁司特和抗抑郁药的处方:2434人在开具抗抑郁药之前首次开具了孟鲁司特处方,2016人以相反顺序开具了药物(r为1.21[95%CI 1.14 - 1.28])。当按哮喘严重程度分层时,我们发现在接受长效哮喘治疗的组中r大于1,但抗抑郁药处方没有增加。

结论

我们发现孟鲁司特的使用与开具抗抑郁药的风险之间存在微弱关联,不太可能具有临床相关性。分层分析表明这种关联可能与哮喘有关,而非孟鲁司特。

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