Analysis: Impact of bupropion use on open-angle glaucoma risk

Take-home:

The widely used antidepressant bupropion appeared to protect against open-angle glaucoma in an analysis of a large health-care claims database.

By Nancy Groves; Reviewed by Joshua D. Stein, MD, MS

Ann Arbor, MI-Use of the antidepressant bupropion may be beneficial in reducing the risk of open-angle glaucoma due to its properties as a tumor necrosis factor (TNF) inhibitor.

Analysis of bupropion use among patients in a large health-care claims database suggested that bupropion had a dose-response related protective effect, said Joshua D. Stein, MD, MS, assistant professor, ophthalmology and visual sciences, Kellogg Eye Center, University of Michigan, Ann Arbor.

“These findings must be confirmed before we would start to recommend prescribing bupropion specifically for glaucoma, but this study’s results, coupled with basic science models showing that TNF-blocking agents are neuroprotective, offer promise for novel future ways to treat glaucoma,” Dr. Stein said.

A growing body of evidence in both human and animal models suggests that elevated IOP acts as a stressor that can promote neuroinflammation, causing the production of cytokines such as TNF. Studies in animal models have shown that patients with glaucoma have high levels of TNF, and a 2012 study reported that TNF blockers may protect the retinal ganglion cells.

Based on this background, Dr. Stein and his colleagues searched for an FDA-approved drug that had anti-TNF activity that might be useful for glaucoma. They turned to bupropion, a norepinephrine-dopamine reuptake inhibitor thought to lower TNF by increasing cAMP via an increase in monoaminergic or dopaminergic tone.

Testing their hypothesis

The researchers accessed a health-care claims database of all enrollees in a large U.S. managed-care network between Jan. 1, 2001 and Dec. 31, 2011, reviewing records of all ocular and nonocular conditions, the sociodemographic characteristics of enrollees, and all outpatient medications prescribed. This provided a cohort of more than 638,000 beneficiaries eligible for analysis. Next, use of bupropion was identified, and the number of days each enrollee was prescribed bupropion or other antidepressant medication classes was quantified.

“We did a regression model analysis to see if the risk of developing glaucoma differed between patients taking and those not taking bupropion,” Dr. Stein said. “Then we also considered other classes of antidepressants to see if the association was specific to bupropion or was apparent with other medications as well, which would contradict our hypothesis.”

The analysis revealed that 7.1% of enrollees (45,337 individuals) had one or more prescriptions for bupropion; the mean length of time taking the drug was 466 ± 583 days, and the median number of eye-related visits was 5 for both users and nonusers of bupropion.

In addition, the analysis showed that 15,292 eligible enrollees (2.4%) developed incident open-angle glaucoma; the rate of disease development was lower in bupropion users (1.8%) than in non-users (2.4%, p < 0.0001).

“After we adjusted for other possible factors in the regression model, the patients taking bupropion had a 0.6% reduced risk for glaucoma for every additional month of use (HR = 0.994, [95% CI: 0.989-0.998], p = 0.007). Over a 4-year period, that amounts to roughly a 29% reduced risk for open-angle glaucoma,” Dr. Stein said.

Analysis of the tricyclic antidepressants and selective serotonin reuptake inhibitors did not show a statistically significant reduction in the risk of glaucoma.

“The study suggests that the apparent effect is specific to this particular antidepressant agent,” Dr. Stein added.

Examining the relationship

The next step was to explore the relationship between the amount of bupropion taken during patients’ time in the health plan and development of glaucoma.

“We found that the group taking the most bupropion had the greatest risk reduction. That also helped support our hypothesis,” Dr. Stein said.

In the analysis, 36 to 48 months of bupropion treatment was associated with a 22% reduced hazard of glaucoma compared with non-users (HR = 0.78, [95% CI:0.60-1.00] p = 0.05).

The researchers also found that the association between bupropion use and glaucoma onset did not differ on the basis of the clinical indication for which the drug was prescribed-for example, a mood disorder or smoking cessation (p  ≥ 0.65).

Joshua D. Stein, MD, MS

E: jdstein@umich.edu

This article is adapted from Dr. Stein’s presentation at the 2014 meeting of the Association for Research in Vision and Ophthalmology. Dr. Stein did not report any commercial relationships.