Clinical Signs of Pregabalin Toxicity
Pregabalin overdose primarily causes central nervous system depression manifesting as reduced consciousness, somnolence, dizziness, confusional state, agitation, and restlessness, with more severe cases progressing to coma requiring mechanical ventilation. 1
Primary Clinical Manifestations
Neurological Signs
- Reduced consciousness and altered mental status are the hallmark features, ranging from confusion to deep coma 1, 2
- Somnolence and dizziness occur in a dose-dependent manner and represent the most common adverse effects even at therapeutic doses 3, 1, 4
- Myoclonic movements can develop, particularly in patients with renal impairment, and may occur even without drug accumulation 5
- Seizures have been reported in overdose situations 1
- Agitation, restlessness, and confusional states are frequently observed 1
Cardiovascular Manifestations
- Heart block has been documented in overdose cases 1
- Cardiovascular stability is generally maintained in most cases, even with significant overdoses 2, 6
Psychiatric Symptoms
- Depression and anxiety may paradoxically worsen 1
- Encephalopathy can develop, particularly when combined with myoclonus 5
Time Course and Severity
Clinical deterioration typically occurs 3 hours post-ingestion, even when patients initially appear asymptomatic 2. The onset of adverse effects is most frequently detected in the early days of pregabalin therapy 7.
Peak pregabalin concentrations associated with significant toxicity range from 13-66.5 mg/L, though toxicity severity does not always correlate directly with serum levels 2, 6, 5.
Risk Factors for Enhanced Toxicity
Concomitant Medications
- Opioid co-administration significantly increases the incidence of somnolence and dizziness 7
- CNS depressants (benzodiazepines, other sedatives) potentiate toxicity and have been implicated in fatal overdoses 1, 7, 6
Patient-Specific Factors
- Renal impairment increases risk, though myoclonic encephalopathy can occur even with therapeutic pregabalin levels in acute renal failure 5
- Elderly patients are at higher risk for serious adverse effects including falls, confusion, and sedation 3
Management Approach
Immediate Supportive Care
There is no specific antidote for pregabalin overdose; management is entirely supportive 1.
- Airway protection is paramount: Endotracheal intubation and mechanical ventilation may be required for patients with significant CNS depression 1, 2
- Monitor vital signs continuously and observe clinical status closely 1
- Contact Poison Control for up-to-date management guidance 1
Decontamination Considerations
- Gastric lavage or emesis may be attempted if presentation is early, with appropriate airway precautions 1
- These interventions are only useful within the first 1-2 hours post-ingestion given pregabalin's rapid absorption 4
Enhanced Elimination
Hemodialysis removes approximately 50% of pregabalin in 4 hours and should be considered in severe cases 1. However, multiple case reports demonstrate successful management with supportive care alone, even with very high serum concentrations (up to 66.5 mg/L) 2, 6.
The decision to pursue hemodialysis should be based on clinical severity rather than serum levels alone, as patients with significant toxicity have recovered with conservative management 2, 6.
Specific Interventions
- Discontinue pregabalin immediately upon recognition of toxicity 5
- Withdraw or reduce doses of concomitant CNS depressants, particularly opioids 7
- Myoclonus typically resolves within 24 hours of drug discontinuation with supportive care 5
- Full neurological recovery generally occurs within 48 hours 5
Critical Pitfalls to Avoid
- Do not assume cardiovascular or respiratory stability will persist: Patients may initially appear well but deteriorate hours later 2
- Do not rely solely on serum pregabalin levels to guide management decisions, as clinical toxicity can occur at therapeutic concentrations in certain populations 5
- Do not overlook polypharmacy: Deaths have occurred with pregabalin in combination with other CNS depressants, though lone pregabalin overdose fatalities are rare 1, 6
- Do not abruptly discontinue pregabalin in chronic users outside the acute overdose setting, as withdrawal symptoms may occur 4