What is the cause of Baclofen (GABA receptor agonist) toxicity?

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From the Guidelines

Baclofen toxicity should be managed with supportive care, including airway management and ventilatory support if needed, along with fluid administration, and in severe cases, hemodialysis may be necessary to remove baclofen from the bloodstream. Baclofen toxicity occurs when there are excessive levels of the muscle relaxant baclofen in the body, typically due to overdose, impaired kidney function, or drug interactions. Symptoms of baclofen toxicity include drowsiness, confusion, respiratory depression, seizures, coma, and in severe cases, death. The toxicity develops because baclofen is a GABA-B receptor agonist that inhibits neurotransmission in the central nervous system, and excessive inhibition leads to widespread CNS depression. Risk factors include renal impairment (as baclofen is primarily excreted by the kidneys), older age, concomitant use of other CNS depressants like benzodiazepines or alcohol, and intentional or accidental overdose.

Some key points to consider in the management of baclofen toxicity include:

  • Careful dose titration, especially in patients with kidney disease
  • Monitoring for drug interactions
  • Patient education about proper medication use and storage
  • Prompt recognition and management of baclofen toxicity to prevent serious complications, as noted in studies such as 1 It's also important to note that baclofen can worsen obstructive sleep apnea (OSA) by provoking upper airway collapse during sleep and affecting central apnoeas or hypoventilation during sleep by depressing respiratory drive, as discussed in 1. However, the most recent and highest quality study on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning, 1, does not specifically address baclofen toxicity, but its recommendations on the management of life-threatening toxicity due to poisoning can be applied to baclofen toxicity.

From the FDA Drug Label

WARNINGS a. Neonatal Withdrawal Symptoms:Withdrawal symptoms have been reported starting hours to days after delivery in neonates whose mothers were treated with oral baclofen throughout pregnancy. The symptoms of withdrawal in these infants have included increased muscle tone, tremor, jitteriness, and seizure b. Abrupt Drug Withdrawal:Hallucinations and seizures have occurred on abrupt withdrawal of baclofen c. Impaired Renal Function:Because baclofen is primarily excreted unchanged through the kidneys, it should be given with caution, and it may be necessary to reduce the dosage.

Baclofen toxicity can occur due to several reasons, including:

  • Abrupt withdrawal: Hallucinations and seizures have occurred on abrupt withdrawal of baclofen 2.
  • Impaired renal function: Baclofen should be given with caution in patients with impaired renal function, as it may be necessary to reduce the dosage 2.
  • Neonatal withdrawal: Withdrawal symptoms, including increased muscle tone, tremor, jitteriness, and seizure, have been reported in neonates whose mothers were treated with oral baclofen throughout pregnancy 2.

From the Research

Baclofen Toxicity

Baclofen toxicity can occur due to various reasons, including:

  • Intentional self-poisoning (acute baclofen poisoning) 3
  • Accumulation of therapeutic dose in the setting of impaired kidney function 3
  • Abrupt decrease in the dose of baclofen due to surgery or a rapid tapering program, leading to severe baclofen withdrawal syndrome 4
  • Intrathecal baclofen (ITB) treatment, which can cause life-threatening complications, including respiratory difficulty, generalized seizures, and coma 5

Clinical Presentation

The clinical presentation of baclofen toxicity can include:

  • Coma 3, 6, 5
  • Respiratory depression 3, 6, 5
  • Autonomic disturbances 6
  • Seizures 3, 6, 5
  • Hyporeflexia 4, 6
  • Flaccidity 4, 6
  • Hemodynamic instability, including hypotension and hypertension 4, 7
  • Cardiovascular effects, including ST elevations on ECG and apical ballooning on echocardiogram 7

Management

The management of baclofen toxicity includes:

  • Discontinuation of baclofen 3
  • Respiratory support 3, 6, 5
  • Seizure treatment 3
  • Supportive treatment, including intravenous fluids and hemodialysis 4, 5
  • Extracorporeal treatments (ECTRs) may be considered in certain cases, although their use is controversial 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose.

Journal of toxicology. Clinical toxicology, 1998

Research

Intrathecal baclofen toxicity and deep coma in minutes.

The journal of spinal cord medicine, 2006

Research

An intoxication mimicking brain death: baclofen.

Acta neurologica Belgica, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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