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) (eg, sedatives or 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 US 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.

Outcome: 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, as 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 HR for AMS with PPIM coprescribing was 2.14 (95% CI, 1.69-2.71); 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, 3.22 [95% CI, 2.55-4.06]) and falls (HR, 2.77 [95% CI, 2.27-3.38]) compared with nonfrail individuals without PPIM coprescribing.

Limitations: Outcome ascertainment bias; residual confounding.

Conclusions: Compared with 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.

Plain-language summary: Among people on dialysis, gabapentinoids may lead to confusion and falls. Often they are prescribed with other sedatives drugs or opioids, which can increase these risks. This study of adults with kidney failure receiving maintenance dialysis in the United States found that those who were prescribed both gabapentinoids and other psychoactive drugs were more likely to have confusion and falls compared with those who only took gabapentinoids. These relationships were seen at all levels of frailty although the relative risk of confusion related to an additional psychoactive drug was somewhat lower in the setting of greater frailty. Clinicians should consider elevated risks of confusion and falls when prescribing psychoactive drugs to patients receiving dialysis who are also prescribed gabapentinoids.