Risk Factors for Falls in Older Depressed Adults Treated with Bupropion: An Analysis of the OPTIMUM Randomized Clinical Trial

Background: Antidepressant augmentation with bupropion was recently demonstrated to increase fall risk in older adults, though specific subpopulations that may have increased risk have not yet been identified. Objective: To determine risk factors for falls in older adults with Major Depressive Disorder (MDD) receiving bupropion augmentation. Design: Older adults with major depression were followed for approximately ten weeks during a randomized controlled trial (RCT) with three treatment arms, including bupropion augmentation. Data from the bupropion augmentation arm, which had higher fall rates, were analyzed. Participants: 194 older adults with MDD randomized to bupropion augmentation. Main Measures: Participants’ report of falls during biweekly study visits. Key Results: The following baseline characteristics were significantly correlated (p < 0.05) with total number of falls: number of falls during the previous 6 months (r = 0.42), burden of physical illness measured with the Cumulative Illness Rating Scale-Geriatric (r = 0.26), physical function score on the Patient-Reported Outcomes Measurement Information System (r = -0.23), and baseline Patient Health Questionnaire-9 Score (r = 0.16). There were significant main effects of bupropion dosage level (low, medium, or high) (p = 0.04) and number of falls during the six months prior to study entry (p < 0.001). Study fall rates extrapolated out to the number of falls per year of treatment for subgroups distinguished by dosage level and prior falls ranged from 1.39 falls/year (no history of falls, low dosage bupropion) to 12.32 falls/year (3 + falls during the 6 months prior to study entry, high dosage bupropion). Conclusions: The risk of falls during bupropion augmentation is a function of the patient’s personal history of falls and the dosage of bupropion. Careful patient selection and personalization of dosing strategy might reduce the risk of falls in older depressed patients treated with bupropion.