Clinicians may fail to recognize common side effects of drugs like gabapentin - which are frequently prescribed for nerve pain - leading them to prescribe unnecessary medications that cause yet more side effects. This phenomenon, known as a "prescribing cascade," is increasingly seen as a danger to older patients.
In this case, gabapentinoids - which include gabapentin (Neurontin) and pregabalin (Lyrica) - may cause leg swelling, leading doctors to suspect heart failure and then prescribe diuretics that can cause kidney injury, light headedness, and falls.
Researchers tracked the medical records of 120 older veterans, most of whom were male and were long-term users of five or more medications. All had taken gabapentinoids, followed by loop diuretics, which are prescribed for fluid buildup, a possible symptom of heart failure.
"Gabapentinoids are non-opioids, and prescribers associate them with a relatively favorable safety profile," Michael Steinman, MD, a professor of Medicine at UCSF and senior author of the study said, noting that these prescriptions have almost doubled in a decade. "Patients taking them should regularly check in with their doctor to assess whether this is the best treatment for them and consider other options, including non-drug alternatives that might be more appropriate."
Following gabapentinoids, the patients developed swelling in the legs or feet, but only 4 of the veterans' physicians considered the drugs as the culprit, while 69 considered other causes. This included heart failure, and another condition called venous stasis in which abnormal blood flow puts pressure on veins, sometimes leading to ulcers. Although none of the veterans had these conditions in the year before they started taking gabapentinoids, just one doctor discontinued the drug. Close to 1 in 5 patients underwent imaging to rule out life-threatening conditions that the doctors suspected were the cause of their leg swelling.
All of the physicians, including those who suspected gabapentinoids as the cause, prescribed loop diuretics, such as Lasix. Within two months, 28 patients had symptoms that may have been due to the new drugs, such as worsening kidney functioning, dizziness, and blurred vision, and low sodium or potassium, which can disrupt critical body functions. Six were hospitalized or evaluated in the Emergency Department.
Gabapentinoids may be prescribed at unnecessarily high doses or for conditions that they may not help. In these cases, doctors should consider not prescribing these drugs - or giving lower doses to lessen the risk of prescribing cascades and other side effects."
Matthew Growdon, MD, assistant professor of Medicine at UCSF, first author of the paper
Source:
Journal reference:
Growdon, M. E., et al. (2025). Decision-Making and Downstream Outcomes of the Gabapentinoid-Diuretic Prescribing Cascade. JAMA Network Open. doi: 10.1001/jamanetworkopen.2025.45274. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2842165