Association of Coprescribing of Gabapentinoid and Other Psychoactive Medications With Altered Mental Status and Falls in Adults Receiving Dialysis

Rationale & objective: Prescribing psychoactive medications for patients with kidney disease is common, but for patients receiving dialysis, some medications may be inappropriate. We evaluated the association of coprescribing gabapentinoids and other psychoactive potentially inappropriate medications (PPIMs) (e.g., sedatives, opioids) with altered mental status (AMS) and falls, and whether the associations are modified by frailty.

Study design: Observational cohort study.

Setting: & Participants: Adults receiving dialysis represented in the United States Renal Data System who had an active gabapentinoid prescription and no other PPIM prescriptions in the prior 6 months.

Exposure: PPIM coprescribing, or the presence of overlapping prescriptions of a gabapentinoid and ≥1 additional PPIM.

Outcomes: Acute care visits for AMS and injurious falls.

Analytical approach: Prentice-Williams-Petersen Gap Time models estimated the association between PPIM coprescribing and each outcome, adjusting for demographics, comorbidities, and frailty (assessed by a validated frailty index (FI)). Each model tested for interaction between PPIM coprescribing and frailty.

Results: Overall, PPIM coprescribing was associated with increased hazard of AMS (HR: 1.66 [95% CI 1.44, 1.92]) and falls (HR: 1.55 [95% CI 1.36, 1.77]). Frailty significantly modified the effect of PPIM coprescribing on the hazard of AMS (interaction p=0.01), but not falls. Among individuals with low frailty (FI=0.15), the hazard ratio for AMS with PPIM co-prescribing was 2.14 (95% CI: 1.69, 2.71); while for individuals with severe frailty (FI=0.34), the hazard ratio for AMS with PPIM coprescribing was 1.64 (95% CI: 1.42, 1.89). Individuals with PPIM coprescribing and severe frailty (FI =0.34) had the highest hazard of AMS [HR 4.04 (95% CI: 3.20, 5.10)] and falls [HR 2.77 (95% CI: 2.27, 3.38)] compared to non-frail individuals without PPIM coprescribing.

Limitations: Outcome ascertainment bias; residual confounding.

Conclusions: Compared to gabapentinoid prescriptions alone, PPIM coprescribing was associated with an increased risk of AMS and falls. Clinicians should consider these risks when coprescribing PPIMs to patients receiving dialysis.