A new VA/UCSF study shows this edema-triggered prescribing cascade occurs when clinicians treat the swelling with more medications, sometimes overlooking gabapentinoids as the underlying cause.

Gabapentin remains widely prescribed, with off-label use estimated up to 95% and 15.5 million patients in 2024, underscoring the potential scale of prescribing cascades and the need for careful prescribing.

Lead author Dr. Matthew Growdon calls on clinicians to re-evaluate necessity and dosing and to consider non-drug or lower-dose alternatives to reduce cascading adverse effects.

None of the 120 veterans had prior heart failure or venous insufficiency, and about one-fifth underwent imaging; only one doctor discontinued gabapentinoids after edema emerged.

After diuretic initiation, all patients saw loop diuretics prescribed, with adverse effects including kidney function changes, dizziness, blurred vision, and electrolyte disturbances within two months; several hospitalizations or ED visits occurred.

Within two months, 28 veterans experienced additional side effects from the cascade, and six required hospitalization or emergency evaluation.

Gabapentinoids, including gabapentin and pregabalin, can cause leg swelling that is often mistaken for heart failure, prompting diuretic use and a dangerous cascade of additional side effects.

The research highlights the risk of prescribing cascades when non-opioid gabapentinoids are used at high doses or for conditions with limited evidence of benefit, necessitating careful reevaluation and alternatives.

Gabapentin and relatedGabapentinoids are widely used off-label for pain, despite safety warnings and questions about efficacy for those uses.

Study examples show patients rapidly escalating from gabapentin to diuretics, resulting in dizziness, imbalance, and other safety concerns from polypharmacy.

In a cohort of older veterans, swelling was frequently misattributed to heart failure or venous issues rather than gabapentinoids, with very few doctors considering the drugs as the cause.

The JAMA Network Open study underscores that gabapentinoids are often viewed as having a favorable safety profile, which may contribute to overprescribing and missed drug-induced symptoms.

Experts urge regular reassessment of gabapentinoid therapy, including lowering doses or stopping the medication when benefits do not justify risk, especially at high doses or for marginal indications.