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

Amanda C. Randolph, Yu Li Lin, Elena Volpi, Yong Fang Kuo

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJournal of the American Geriatrics Society
DOIs
StatePublished - Jan 1 2019

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Diabetic Neuropathies
Tricyclic Antidepressive Agents
Peripheral Nervous System Diseases
gamma-Aminobutyric Acid
Confidence Intervals
Prescriptions
Aminobutyrates
Incidence
Diabetes Complications
Pain Management
Medicare
Patient Selection
Cohort Studies
History
Odds Ratio
Pharmaceutical Preparations

Keywords

  • diabetes
  • falls
  • neuropathy
  • pain management

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

@article{706d38d709964295a05d44d1b5adf00d,
title = "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",
author = "Randolph, {Amanda C.} and Lin, {Yu Li} and Elena Volpi and Kuo, {Yong Fang}",
year = "2019",
month = "1",
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doi = "10.1111/jgs.15779",
language = "English (US)",
journal = "Journal of the American Geriatrics Society",
issn = "0002-8614",
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TY - JOUR

T1 - Tricyclic Antidepressant and/or γ-Aminobutyric Acid–Analog Use Is Associated With Fall Risk in Diabetic Peripheral Neuropathy

AU - Randolph, Amanda C.

AU - Lin, Yu Li

AU - Volpi, Elena

AU - Kuo, Yong Fang

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - diabetes

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