Tricyclic Antidepressant and/or γ-Aminobutyric Acid-Analog Use Is Associated With Fall Risk in Diabetic Peripheral Neuropathy

Abstract

Background/objectives: Peripheral neuropathy is a common diabetes complication that can increase fall risk. Regarding fall risk, the impact of pain management using tricyclic antidepressants (TCAs) or γ-aminobutyric acid (GABA) analogs is unclear because these medications can also cause falls. This study investigates the impact of these drugs on fall and fracture risk in older diabetic peripheral neuropathy (DPN) patients.

Design: Historical cohort study with 1-to-1 propensity matching of TCA/GABA-analog users and nonusers.

Setting: Nationally representative 5% Medicare sample between the years 2008 and 2010.

Participants: After applying all selection criteria, 5,550 patients with prescription and 22,200 patients without prescription of TCAs/GABA-analogs were identified. Both patient groups were then stratified for fall history and matched based on propensity of receiving TCAs/GABA-analogs within each group.

Measurements: Patients were followed until the first incidence of fall or the first incidence of fracture during the follow-up period (for up to 5 years).

Results: After matching, users and nonusers were largely similar. After covariate adjustment, TCA/GABA-analog use was associated with a statistically significant increase in fall risk (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 1.03-1.20), but was not associated with fracture risk (adjusted HR = 1.09; 95% CI = 0.99-1.19) in the conventional analysis. Treating TCA/GABA-analog use as a time-dependent covariate resulted in statistically significant associations of TCA/GABA-analog use with both fall and fracture risk (HR = 1.26 [95% CI = 1.17-1.36]; and HR = 1.12 [95% CI = 1.02-1.24], respectively).

Conclusion: Among older patients with DPN, GABA-analogs or TCAs increase fall risk and possibly fracture risk. Use of these medications is therefore a potentially modifiable risk factor for falls and fractures in this population.

Keywords: diabetes; falls; neuropathy; pain management.

Figure 1.. STROBE diagram for selection of TCA/GABA-analog users and non-users.

^aICD-9 codes for peripheral neuropathy: 250.60 and 250.62. ^bIn order to keep as many controls as possible, all subjects in the previous step were assigned January 2008 as the index date. Then the selection criteria were applied to identify eligible subjects. Controls needed for that month were then randomly selected from the eligible subjects. This process was repeated 35 more times for all the months from February 2008 to December 2010.

Figure 2.. Time to the first outcome event for TCA/GABA-analog users (User=Y) and their matched non-users (User=N).

A. Fracture. There was a significant difference between the users and non-users (p=0.005, Log-rank test). B. Fall. There was a significant difference between the users and non-users (p<0. 001, Log-rank test).