Higher Bupropion Doses Increase Fall Risk in Older Adults With Depression

Among older adults with major depressive disorder (MDD) receiving antidepressant augmentation, higher doses of bupropion and a prior history of falls are associated with increased fall risk, according to study findings published in the Journal of General Internal Medicine.

Researchers conducted a secondary analysis of the OPTIMUM pragmatic, multisite randomized clinical trial (ClinicalTrials.gov Identifier: NCT02960763) to determine risk factors for falls in older adults with MDD receiving bupropion augmentation. The primary measurement was reported falls during biweekly study visits.

Older adults aged 60 years and older with treatment-resistant depression who were receiving bupropion augmentation were enrolled in the study. Participants were followed up for approximately 10 weeks, with biweekly assessments documenting medication adherence and falls, defined as a loss of balance resulting in a fall to the ground or a lower level.

The cohort (N=194; mean age, 69.2 years; 69.6% women; 85.1% White) at baseline reported the following: 63.4% had no falls in the previous 6 months, 23.2% had 1 to 2 falls, and 13.6% had 3 or more falls. The mean cumulative illness rating scale-geriatric (CIRS-G) score was 8.6, and the average patient-reported outcomes measurement information system (PROMIS) physical function score was 40.9.

During the study period, 71.1% of participants experienced no falls, 21.1% reported 1 to 2 falls, and 7.7% reported 3 or more falls. Participants with multiple falls accounted for 54.2% of the total falls observed. Dizziness or impaired balance was reported more frequently among participants who experienced falls vs no falls (26.8% vs 18.8%, respectively).

Several baseline factors correlated significantly with fall risk. The strongest association was prior fall history within the previous 6 months (r=0.42). Higher medical comorbidity burden, lower physical function scores, and greater depressive symptom severity were also linked to increased fall totals (r=0.24, r=-0.22, and r=0.16, respectively).

Dose-response analyses showed increasing fall rates with higher bupropion doses. Average fall rates were 0.42, 0.60, and 1.17 falls per 10 weeks for the low-, medium-, and high-dose groups, respectively. When extrapolated annually, projected fall rates ranged from 1.21 falls per year in patients without prior falls to more than 6.82 falls per year in those with multiple prior falls.

Genetic analyses evaluating CYP2B6 polymorphisms related to bupropion metabolism did not demonstrate a statistically significant association with fall risk, although exploratory findings suggested possible trends requiring further investigation.

Study limitations include the relatively short follow-up duration, reliance on self-reported fall data, and smaller subgroup sizes for some dose-response analyses, which may limit generalizability.

Researchers used the cumulative illness rating scale-geriatric (CIRS-G) to measure the number and severity of physical health problems. All participants completed the patient-reported outcomes measurement information system (PROMIS) physical function T-score to measure overall physical functioning. Participants also completed the patient health questionnaire (PHQ)-9 form to assess depression diagnosis.