Predictors of a Gabapentinoid-Loop-Diuretic Prescribing Cascade in U.S. Nursing Home Residents

Abstract

Background: Gabapentinoid-related peripheral edema may prompt loop diuretic prescribing. Nursing home (NH) residents may be especially prone to this prescribing cascade. We estimated the incidence and identified predictors of the gabapentinoid-loop diuretic prescribing cascade in NHs.

Methods: We conducted a retrospective cohort study using 2016-2022 Medicare claims linked with Minimum Data Set assessments. We identified residents aged ≥ 66 years who initiated gabapentinoids in NHs and who had no evidence of loop diuretic use, heart failure, or renal insufficiency during the prior 6 months. The outcome was loop diuretic initiation within 90 days of gabapentinoid initiation. Using multivariable Poisson regression models, we estimated adjusted risk ratios (aRR) with 95% robust confidence intervals to identify predictors. We used pooled logistic regression models to examine the relationship between time-varying gabapentinoid dose and loop diuretic initiation risk.

Results: Among 23,544 residents, 994 (4.2%) experienced a prescribing cascade at a median of 36 days (IQR 15-61) after gabapentinoid initiation. Risk was higher with age 86-90 years (aRR = 1.60) or ≥ 91 years (aRR = 1.38); a diagnosis of chronic pain or fibromyalgia (aRR = 1.16), or diabetes (aRR = 1.23); and receipt of potassium-sparing diuretics (aRR = 1.53), thiazide diuretics (aRR = 1.27), or 15 or more unique medications (aRR = 1.18). Higher (versus lower) weekly gabapentin dose during follow-up was associated with a 1.45 times higher prescribing cascade risk over 13 weeks. Those with Alzheimer's Disease and Related Dementias (aRR = 0.79), or moderate (aRR = 0.72) to severe cognitive impairment (aRR = 0.59) had a lower risk versus those with intact cognition.

Conclusions: Approximately 1 in 20 NH residents who initiate gabapentinoids receives a loop diuretic within 3 months. Potentially modifiable predictors included existing polypharmacy and titrating gabapentinoid doses. NH clinicians should monitor for edema soon after gabapentinoid initiation and consider dose reductions or discontinuation before adding a loop diuretic.

Keywords: adverse drug effects; diuretics; gabapentin; nursing homes; pharmacoepidemiology; polypharmacy.