What is the treatment for pregabalin (Lyrica) toxicity?

Treatment of Pregabalin Toxicity

Pregabalin overdose should be managed primarily with supportive care, including airway protection and monitoring of vital signs, as there is no specific antidote. 1

Initial Management and Supportive Care

The cornerstone of pregabalin toxicity management is aggressive supportive treatment:

• Airway management is paramount - patients may develop significant neurological depression and coma requiring endotracheal intubation and mechanical ventilation, typically occurring 3 hours post-ingestion 2
• Monitor vital signs continuously and observe clinical status closely, as cardiovascular and respiratory stability can deteriorate 1, 3
• Gastric decontamination may be attempted if presentation is early - consider emesis or gastric lavage with usual airway precautions, though clinical utility decreases rapidly after ingestion 1
• Contact Poison Control for up-to-date management guidance 1

Clinical Presentation and Monitoring

Expect the following toxicity patterns:

• Neurological depression is the primary manifestation, ranging from altered mental status to deep coma 2, 4
• Myoclonus can occur, particularly in patients with renal impairment 5
• Toxic-metabolic encephalopathy with confusion, delusions, restlessness, and visual hallucinations, especially when combined with other substances 4
• Rhabdomyolysis and acute kidney injury may complicate severe cases 4
• Peak toxicity typically manifests within 3 hours of ingestion 2

Role of Hemodialysis

Hemodialysis should be considered for severe toxicity, particularly in patients with significant renal impairment or life-threatening symptoms:

• Pregabalin has favorable properties for dialysis removal: low molecular weight (159 Da), low volume of distribution (0.5 L/kg), and no protein binding 5
• Standard hemodialysis achieves approximately 50% clearance in 4 hours with reported clearance rates of 88.8 mL/min 1, 5
• Hemodialysis resulted in immediate symptom resolution in documented cases 5
• However, multiple case reports demonstrate successful management with supportive care alone, even with very high serum concentrations (up to 66.5 mg/L) 2, 3

When to Consider Enhanced Elimination

The decision for hemodialysis versus supportive care alone depends on:

• Severity of neurological depression - deep coma or respiratory failure favors dialysis 2
• Presence of renal impairment - pregabalin accumulation is more problematic in kidney disease 5
• Clinical trajectory - deteriorating patients despite supportive care should receive dialysis 1
• Co-ingestions - polypharmacy overdoses may benefit from enhanced elimination 4, 6

Critical Pitfalls

Avoid these common errors:

• Do not underestimate delayed toxicity - patients may appear stable initially but deteriorate 3+ hours post-ingestion 2
• Screen for polysubstance abuse - pregabalin is frequently combined with opioids, benzodiazepines, ketamine, and other CNS depressants, creating lethal combinations 4, 6
• Recognize that pregabalin toxicity can be severe despite its reputation as relatively safe - deaths have been reported, particularly with co-ingestions 6
• Adjust expectations in renal failure - these patients are at higher risk for toxicity and may require dialysis even at therapeutic doses 5

Prognosis

• Most patients recover fully with supportive care alone, even after massive overdoses (up to 8000 mg reported without notable consequences) 1
• Serum pregabalin concentrations correlate poorly with clinical severity - patients with levels of 20.8 mg/L may be asymptomatic while others at 66.5 mg/L require intubation 2, 3
• The key determinant of outcome is adequate supportive care, not the specific pregabalin level 2, 3