Stein Joshua D, Talwar Nidhi, Kang Jae H, Okereke Olivia I, Wiggs Janey L, Pasquale Louis R
Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2015 Apr 13;10(4):e0123682. doi: 10.1371/journal.pone.0123682. eCollection 2015.
Tumor Necrosis Factor (TNF) mediates retinal ganglion cell death in glaucoma. Anti-TNF drugs are neuroprotective in an animal model of glaucoma. It is unclear whether medications with anti-TNF properties such as bupropion have an impact on the risk of developing open-angle glaucoma (OAG) in humans. The purpose of this study is to determine whether bupropion use alters the risk of developing OAG.
Claims data for beneficiaries age ≥35 years with no pre-existing OAG enrolled in a large nationwide U.S. managed care network continuously for ≥4 years between 2001-2011 was analyzed to identify patients who had been newly-diagnosed with OAG. The amount of bupropion use as captured from outpatient pharmacy claims over a four-year period was also quantified for each beneficiary. Multivariable Cox regression modeling assessed the impact of bupropion and other antidepressant medications on the risk of developing OAG with adjustment for sociodemographic characteristics of the enrollees along with medical and ocular comorbidities.
Of 638,481 eligible enrollees, 15,292 (2.4%) developed OAG. After adjustment for confounding factors including use of other antidepressant medication classes, each additional month of bupropion use was associated with a 0.6% reduced risk of OAG (HR = 0.994, (95% CI: 0.989-0.998), p = 0.007). Compared to nonusers, those with 24-48 months of bupropion use had a 21% reduced hazard (HR=0.79, (CI: 0.65-0.94), p = 0.0099) of OAG. This association did not differ among persons taking bupropion for depression or for other reasons (p-interaction = 0.82). There was no significant association between use of tricyclic antidepressants (HR = 1.000, (CI: 0.997-1.004), p = 0.95) or selective serotonin reuptake inhibitors (HR = 0.999, (CI: 0.997-1.001), p = 0.39) and development of OAG.
These findings suggest bupropion use may be beneficial in reducing the risk of OAG. If prospective studies confirm the findings of this analysis, this may identify a novel therapeutic target for OAG.
肿瘤坏死因子（TNF）介导青光眼患者视网膜神经节细胞死亡。在青光眼动物模型中，抗TNF药物具有神经保护作用。目前尚不清楚具有抗TNF特性的药物（如安非他酮）是否会影响人类患开角型青光眼（OAG）的风险。本研究的目的是确定使用安非他酮是否会改变患OAG的风险。
分析2001年至2011年期间连续4年以上参加美国大型全国性管理式医疗网络且无既往OAG病史的35岁及以上受益人的理赔数据，以确定新诊断为OAG的患者。还对每位受益人在四年期间门诊药房理赔记录中安非他酮的使用量进行了量化。多变量Cox回归模型评估了安非他酮和其他抗抑郁药物对患OAG风险的影响，并对参保者的社会人口学特征以及医疗和眼部合并症进行了调整。
在638481名符合条件的参保者中，15292人（2.4%）患了OAG。在对包括使用其他抗抑郁药物类别等混杂因素进行调整后，安非他酮使用时间每增加一个月，患OAG的风险降低0.6%（风险比[HR]=0.994，95%置信区间[CI]：0.989-0.998，p=0.007）。与未使用者相比，使用安非他酮24至48个月的患者患OAG的风险降低21%（HR=0.79，CI：0.65-0.94，p=0.0099）。服用安非他酮治疗抑郁症或其他原因的患者之间，这种关联没有差异（交互作用p值=0.82）。使用三环类抗抑郁药（HR=1.000，CI：0.997-1.004，p=0.95）或选择性5-羟色胺再摄取抑制剂（HR=0.999，CI：0.997-1.001，p=0.39）与患OAG之间没有显著关联。
这些发现表明，使用安非他酮可能有助于降低患OAG的风险。如果前瞻性研究证实了本分析的结果，这可能会确定一个新的OAG治疗靶点。
