Downstream Harms of Gabapentinoid-Diuretic Prescribing Cascade Often Overlooked

TUESDAY, Dec. 9, 2025 (HealthDay News) — The potential downstream harms in the gabapentinoid (gabapentin and pregabalin)-edema-loop diuretic (LD) prescribing cascade are commonly overlooked, according to a study published online Dec. 2 in JAMA Network Open.

Matthew E. Growdon, M.D., from the University of California, San Francisco, and colleagues examined the key clinician decision-making steps in the gabapentinoid-edema-LD prescribing cascade, as well as the downstream outcomes. The analysis included 120 veterans (66 years and older) who potentially experienced the gabapentinoid-LD prescribing cascade.

The researchers found that most patients (88.3 percent) were taking five or more long-term medications and 60.8 percent had documentation of a differential diagnosis for edema, most commonly referencing congestive heart failure (39.2 percent) and/or venous stasis (13.3 percent). Gabapentinoids were only noted for four patients in the differential (3.3 percent). Nearly all clinicians (96.7 percent) documented the indication for LD, most commonly for lower-extremity edema (86.7 percent), congestive heart failure (13.3 percent), and/or dyspnea (12.5 percent). Roughly one-quarter of patients (23.3 percent) experienced 37 events potentially attributable to LD initiation within 60 days. The most common downstream events included worsening kidney function (7.5 percent), orthostasis (5.8 percent), electrolyte abnormalities (5.0 percent), and falls (4.2 percent). Downstream events were evaluated in the emergency department and/or hospital for six patients.

“Among older veterans who received LD following gabapentinoid initiation and experienced a potential gabapentinoid-LD prescribing cascade, clinicians almost never explicitly considered gabapentinoid adverse drug effects in their treatment of edema,” the authors write.

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