Surreal image representing brainwaves and kidney health, symbolizing pregabalin toxicity.

Pregabalin Toxicity: When a Common Pain Reliever Becomes a Threat

Lena Voss in Health & Wellness December 2025 • 4 min read.

"Unmasking the danger of triphasic waves and encephalopathy linked to pregabalin toxicity, especially in those with kidney issues."

Triphasic waves, initially identified as indicators of liver dysfunction in 1955, are now known to appear in a variety of conditions, including metabolic imbalances, brain infections, and medication toxicities. These waves are frequently observed in patients with pre-existing white matter lesions or general cerebral atrophy, complicating the diagnostic process.

Several medications have been associated with triphasic waves, including common drugs like valproate, baclofen, and lithium. However, continuous triphasic waves caused by medications are rare, with very few instances linking these brainwave patterns to pregabalin toxicity.

This article highlights a case of a patient with underlying white matter lesions who developed triphasic waves and encephalopathy due to pregabalin toxicity, which was exacerbated by renal insufficiency. This case underscores the diagnostic challenges faced when patients with kidney or liver issues present with confusion and unusual brainwave patterns.

Decoding Triphasic Waves and Pregabalin Toxicity

Surreal image representing brainwaves and kidney health, symbolizing pregabalin toxicity.

A 41-year-old woman with a history of type I diabetes, post-pancreas transplant, and chronic kidney disease was admitted to the neurology service with acute encephalopathy. Her medication list included pregabalin for neuropathic pain, alongside other drugs for various conditions. Over the three days before admission, she became increasingly lethargic and showed signs of confusion.

Upon examination, she was only responsive to strong stimuli and displayed disorientation. Neurological assessments showed intact reflexes but an inability to follow commands. Initial laboratory results revealed elevated creatinine levels, indicating worsening kidney function. A lumbar puncture ruled out infections, and an MRI showed extensive white matter hyperintensities, consistent with her long-standing diabetes.

Elevated Creatinine: Serum creatinine was high, indicating kidney dysfunction.
Brain Imaging: MRI showed white matter abnormalities.
EEG Findings: Initial EEG showed abnormal brainwave patterns known as triphasic waves.

The electroencephalogram (EEG) revealed continuous bilateral synchronous discharges, which are triphasic waves. These discharges lessened with patient stimulation but did not respond to lorazepam, a common anti-seizure medication. Considering the patient's declining kidney function and the fact that pregabalin is cleared by the kidneys, doctors suspected pregabalin toxicity. The medication was stopped, and the patient received intravenous fluids. Over the next three days, her mental state significantly improved, and a repeat EEG showed marked improvement, even though her creatinine levels remained high.

The Crucial Takeaway: Recognizing Medication-Induced Encephalopathy

This case highlights the importance of recognizing medication-induced encephalopathy, especially in patients with existing renal or hepatic issues. Discontinuing pregabalin led to significant improvements in the patient’s EEG and mental status, confirming pregabalin toxicity as the cause of her symptoms. Healthcare providers should be vigilant in monitoring patients on pregabalin, particularly those with impaired kidney function, to prevent such complications.

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Everything You Need To Know

What exactly is pregabalin toxicity and who is most at risk?

Pregabalin toxicity refers to the harmful effects that occur when there's too much pregabalin in the body. This is especially dangerous for individuals with kidney problems because pregabalin is cleared from the body by the kidneys. If the kidneys aren't working well, pregabalin can build up, leading to potential toxicity. This can manifest as encephalopathy, a condition affecting brain function.

What are triphasic waves, and what do they signify in relation to pregabalin?

Triphasic waves are abnormal brainwave patterns that can be detected using an electroencephalogram (EEG). While they were initially linked to liver dysfunction, it's now recognized that they can appear in various conditions such as metabolic imbalances, brain infections, and medication toxicities. In the context of pregabalin toxicity, the presence of triphasic waves on an EEG can indicate that the medication is affecting brain function.

What is encephalopathy, and how is it related to pregabalin toxicity?

Encephalopathy is a general term referring to a disease or malfunction of the brain that alters brain function or structure. It can cause a wide range of neurological symptoms, including changes in mental status like confusion, lethargy, and disorientation. In the case of pregabalin toxicity, encephalopathy can be a significant complication, indicating that the drug is negatively impacting the brain.

Why is renal insufficiency or kidney dysfunction so important when considering pregabalin toxicity?

Renal insufficiency, also known as kidney dysfunction, means the kidneys are not working as efficiently as they should to filter waste and excess fluids from the blood. This is significant in the context of pregabalin toxicity because pregabalin is primarily eliminated from the body through the kidneys. When kidney function is impaired, pregabalin can accumulate in the body, increasing the risk of toxic effects on the brain, potentially leading to encephalopathy and the appearance of triphasic waves.

What is medication-induced encephalopathy, and why is it important to recognize?

Medication-induced encephalopathy refers to brain dysfunction caused by a drug. It is important to recognize because many medications are known to cause confusion or other neurological symptoms, particularly in patients with liver or kidney problems that affect how drugs are processed and eliminated. Identifying medication-induced encephalopathy is crucial because stopping the offending medication can lead to significant improvements in the patient's condition, as seen with pregabalin toxicity.