(301) Buprenorphine and Tramadol Prescriptions in Major Depressive Disorder Settings

Publication Number: 632

Background: Evidence from pre-clinical and clinical studies have demonstrated the efficacy of opioids in the pharmacotherapy of major depressive disorder (MDD), with buprenorphine and tramadol being the most widely studied. With gains in the understanding of the beneficial role buprenorphine and tramadol play in the MDD setting, so have an increase in their off-label use in MDD been documented. However, there is scant population-based evidence characterizing the pattern of use and safety profile of these opioids in the MDD setting.

Objectives: To characterize the use and safety profile of buprenorphine and tramadol in a real-world target population with MDD.

Methods: We performed a retrospective new-user cohort study of privately insured US adults with MDD, aged 18 to 64 years, who initiated buprenorphine or tramadol between January 2007 and December 2014 (index date) in the IQVIA PharMetrics® Plus for Academics Database. We ascertained the cumulative incidence of opioid exposure, the primary outcome of serious acute adverse events (composite of respiratory depression, seizure, myocardial infarction, kidney injury, liver injury, and hypoglycemia), and the secondary outcome of all-cause emergency room department visits and hospitalizations. Cumulative incidence was computed using Poisson regression, and inverse probability weighted Cox model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the primary and secondary outcomes comparing tramadol users to buprenorphine users.

Results: A total of 7,218 buprenorphine new users and 128,539 tramadol new users were included in the study. The median number of prescriptions dispensed per month (and the average days' supply per prescription) was 2 (20 days) for buprenorphine and 35 (23 days) for tramadol. There was a statistically significant linear trend in the cumulative incident use of buprenorphine or tramadol from year 2007 to 2014. Compared to buprenorphine, tramadol was associated with a statistically significant increase in the occurrence of serious opioid-related acute adverse events (HR: 1.18; 95% CI: 1.16, 1.21) and a statistically significant reduction in all-cause ER visits and hospitalizations (HR: 0.96; 95% CI: 0.95, 0.97).

Conclusions: In commercially insured adults with MDD, the off-label use of buprenorphine and tramadol was common. The risk of serious adverse events did differ between buprenorphine and tramadol, with tramadol associated with an increase in the occurrence of serious acute adverse events and a reduction in all-cause ER visits and hospitalizations. These findings warrant enhanced clinical guidelines to ensure appropriate use of both opioids and patient safety, especially given their highly prevalent off-label use in the MDD setting.