• Baclofen is a muscle relaxant & antispasmodic commonly used as an adjust therapy for patients with chronic pain and/or spasticity associated with spinal-cord disease.
• It primarily targets receptors in the spinal cord resulting in muscle relaxation. At higher doses it loses this specificity and distributes to the brain causing sedative effects.
• Baclofen toxicity can be life-threatening and is often associated with depressed consciousness, coma, and seizures.
• Patients at greatest risk for Baclofen toxicity are those with acute oral ingestions >200mg; have underlying or new renal impairment; or use intrathecal pumps.

Pathophysiology

• Baclofen is a GABA agonist that binds to GABA-B receptors in the brain and spinal cord.
• At therapeutic concentrations, Baclofen targets the spinal cord to cause muscle relaxation.
• At toxic concentrations, Baclofen loses specificity for the spinal cord and begins to exert greater effect on the brain.

Toxicokinetic 

• High bioavailability with rapid absorption and time to peak effect <2hrs.
• Half-life is ~2-6hrs in healthy patients but can be markedly prolonged in the context of overdose or renal impairment.
• Largely renally excreted with the remainder being hepatically metabolized.
• Intrathecal administration has a slower onset and time to peak effect.

History and Physical

• Symptoms and severity can vary widely.
• Mild toxicity usually presents with nonspecific CNS depression (lethargy, confusion, headaches, and nausea) which can progress to myoclonus and hypotonia.
• Moderate-to-severe toxicity is associated with severe CNS depression, respiratory failure, nonconvulsive status, complete flaccidity, and coma with loss brainstem reflexes mimicking brain death.
• Autonomic abnormalities include hypothermia, hypotension, and bradycardia; but paradoxical hypertension and tachycardia have also been reported.
• Cardiac conduction abnormalities include heart block, prolonged QT interval, premature atrial contractions, or SVT.

Investigations

• Measuring plasma concentration is possible, but not routine and does not change management.
• EEG can assist with diagnosis and identify complications (i.e., nonconvulsive status epilepticus).

• Discuss case with poison center.
• There is no specific antidote for baclofen toxicity.
• Supportive care includes:
  • Activated charcoal 1g/kg PO/NG can be considered if the timeline is appropriate and airway is protected, but its efficacy in adults is unclear.
  • CNS and/or respiratory depression may require securing airway.
  • Treat hypotension with IV fluids. Reserve vasopressors for refractory cases.
  • Treat bradycardia with atropine if symptomatic.
  • Treat seizures with benzodiazepines.

• Dialysis
  • HD has been shown to dramatically reduce drug half-life in patients with renal impairment while evidence demonstrating statistically significant reductions in drug half-life in patients with normal renal function is mixed.

• In cases of rapid clearance (hemodialysis) or abrupt cessation (i.e., stopping an intrathecal pump), clinicians should be prepared to manage Baclofen withdrawal as this is also life threatening.

Disposition

• Admit symptomatic ingestions and consult ICU for cases with airway compromise, hemodynamic instability, or significant CNS manifestations.
• For oral ingestions, baclofen should be held, but restarted when symptoms have resolved to avoid life-threatening withdrawals.
• For overdoses related to an intrathecal pump malfunction, the pump should be stopped. Re-initiation should be planned within 48 hours of stoppage to prevent withdrawal.

Prognosis

• Outcomes are good if patients are stabilized early.
• Most patients will demonstrate improvement of their mental status within 24 – 48 hours.
• Large overdoses (up to 1 to 2g) are more likely to be fatal.
• Overdoses stemming from intrathecal pump malfunction tend to have poorer outcomes.

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4. Dease NM, Kershner EK, Wills BK. Baclofen Toxicity. [Updated 2023 Mar 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK580550/

   
   

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