Pregabalin Toxicity: When a Common Pain Reliever Becomes a Threat
"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.
Reported Toxicity Patterns
The dose-toxicity study describes isolated pregabalin poisonings as generally causing mild symptoms, although seizures and coma have been reported rarely. Its data included prospective cases collected by the Dutch Poisons Information Centre from April 4, 2014, to October 4, 2016, as well as published case reports and case series. A separate report describes prerenal azotemia that may have elevated serum pregabalin and caused toxic encephalopathy with triphasic waves; the patient’s mental status recovered after fluid therapy and discontinuation of pregabalin.
Evidence-Gathering Approach
The cited dose-toxicity evaluation collected data on isolated pregabalin poisonings from a prospective Dutch Poisons Information Centre study conducted from April 4, 2014, through October 4, 2016. The source describes this research method but does not specify an accepted bedside treatment protocol. Because the evaluation focused on isolated poisonings, the excerpt does not establish how its findings apply to cases involving co-ingestions.
A Reported PRES Case
A 2022 Cureus report describes the first known case of posterior reversible encephalopathy syndrome (PRES) after pregabalin abuse. The report situates the case among earlier accounts of acute pregabalin toxicity associated with neuropsychiatric symptoms. Those accounts included an older patient with diabetic nephropathy and hypertension who accidentally overdosed and developed altered mental status attributed to reversible toxic encephalopathy.
Decoding Triphasic Waves and 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.
- 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.
A New Systematic Review
The article “Misuse of Pregabalin and Gabapentin: A Second Systematic Review” aims to update previous reviews of gabapentinoid misuse, dependence, or overdose. Its background says a 2017 systematic review and a 2021 update identified 114 studies. The new review searched PubMed for studies published from September 1, 2020, to January 24, 2025.
Limitations in the Evidence
The Cochrane review of pregabalin for chronic neuropathic pain in adults reports that the evidence had a high risk of bias, mainly because of small study size in nine studies. It also says many studies had unclear risk of bias, chiefly due to incomplete outcome data, study size, and allocation concealment. These limitations concern the chronic-pain evidence assessed by that review and do not, by themselves, establish poisoning outcomes.
Postmortem Concentration Comparison
A postmortem toxicology study on pregabalin and gabapentin abuse reported a median pregabalin blood concentration of 15 mg/L in the abuser group. The median was 5.8 mg/L in the other cases. The supplied result compares those groups but does not report a concentration threshold for toxicity.
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.
Zebrafish Toxicity Research
A study published in Scientific Reports proposes to investigate pregabalin’s neurotoxic effects using a zebrafish model. Its stated objective is to predict and verify potential toxic mechanisms and targets. The source describes this as the study’s aim, not as an established finding about human toxicity.
Recognition and Breathing Risks
In a reported patient with renal insufficiency, discontinuing pregabalin improved the EEG despite ongoing renal insufficiency, supporting pregabalin toxicity as an explanation for triphasic waves and encephalopathy. The FDA warns that pregabalin or gabapentin can cause serious breathing difficulties in patients with respiratory risk factors. These include opioid pain medicines or other central nervous system depressants and conditions such as chronic obstructive pulmonary disease that reduce lung function.