Baclofen Reversal: No Specific Antidote Exists
There is no specific reversal agent or antidote for baclofen overdose or toxicity 1. Management is entirely supportive, focusing on discontinuation of the drug and aggressive supportive care.
Management of Baclofen Overdose
Immediate Actions
- Discontinue baclofen immediately upon recognition of toxicity 1
- Provide intensive supportive care including airway management, mechanical ventilation if needed, and hemodynamic support 2, 3
- Consider activated charcoal to reduce absorption in acute oral overdose if presenting early 4
Hemodialysis Considerations
- Hemodialysis is effective for removing baclofen and can shorten recovery time, even in patients with normal renal function 3, 5
- Initiate hemodialysis in severe cases with worsening clinical status, particularly with significant neurologic depression, respiratory failure, or hemodynamic instability 2, 3
- Use high-efficiency, high-flux dialyzers with blood flow rates of 200-250 mL/min 3
- Clinical improvement typically occurs within 3-6 hours of initiating hemodialysis 3
Important caveat: While baclofen is highly protein-bound, making it theoretically difficult to dialyze, clinical case reports demonstrate clear efficacy of hemodialysis in severe toxicity 2, 3, 5.
Management of Intrathecal Baclofen Withdrawal
This is a distinct and potentially catastrophic scenario requiring different management:
Acute Withdrawal Management
- Restore intrathecal baclofen infusion as soon as possible - this is the definitive treatment 4
- High-dose intravenous benzodiazepines can be lifesaving as a temporizing measure before intrathecal therapy is resumed 4
- High-dose oral baclofen may be attempted, though acute withdrawal can still occur despite this intervention 4
- Low-dose propofol infusion in selected cases in intensive care settings 1
Clinical Presentation
Intrathecal baclofen withdrawal evolves over 1-3 days and presents with 4:
- High fever and altered mental status
- Rebound spasticity and muscle rigidity
- Visual and auditory hallucinations
- Anxiety, agitation, delirium
- Tachycardia and seizures
- Can progress to rhabdomyolysis, multiorgan failure, and death
Key Clinical Pitfalls
- Do not rely on oral baclofen alone for intrathecal baclofen withdrawal - it may be insufficient 4
- Baclofen is not dialyzable in standard circumstances due to high protein binding, but hemodialysis remains effective in severe overdose through unclear mechanisms 2, 3
- Dose reduction is critical in renal impairment: reduce dose with eGFR 30-60 mL/min/1.73m², avoid entirely with eGFR <30 mL/min/1.73m² or on dialysis 2
- Monitor for drug interactions: NSAIDs like ibuprofen can precipitate renal insufficiency, reducing baclofen clearance and causing toxicity 6