Association of pulmonary tuberculosis and ethambutol with incident depressive disorder: A nationwide, population-based cohort study

Background: Inflammatory responses from chronic infection might affect the brain and increase the risk of depressive disorder. However, the temporal association between chronic infection (eg, tuberculosis [TB]) and incident depressive disorder has not been prospectively evaluated. Objective: To determine the association of pulmonary tuberculosis (PTB) and anti-TB drugs with incident depressive disorder (ICD-9-CM codes 296.2x-296.3x, 300.4, and 311.x). Method: From January 1, 2000, we identified adult patients with PTB from the Taiwan National Health Insurance Research Database. A control cohort without PTB, matched for age (± 5 years), sex, comorbidities, and income level, was selected for comparison. The 2 cohorts were followed until December 31, 2011, and observed for occurrence of depressive disorder. Results: Of the 23,145 patients (4,629 study patients and 18,516 matched controls), 302 (1.3%) had depressive disorder during a mean follow-up period of 6.53 years, including 79 study patients (1.71%) and 223 controls (1.20%). After adjusting for age, sex, comorbidities, and income level in the Cox proportional hazards model, PTB was found to be an independent risk factor of incident depressive disorder (adjusted hazard ratio [HR], 1.74; 95% CI, 1.35-2.25). The risk of incident depressive disorder was significantly higher (adjusted HR, 2.54; 95% CI, 1.19-5.45) in patients with TB who received more than 60 defined daily doses (DDDs) of ethambutol, and the effect was dose-dependent. Conclusions: PTB patients had a higher risk of incident depressive disorder, particular in those with an ethambutol dose of more than 60 DDDs. Depressive disorder should be sought in patients following tuberculosis.