What are the symptoms of Baclofen (GABA receptor agonist) toxicity?

From the Guidelines

Baclofen toxicity should be managed with immediate discontinuation of the drug, supportive care, and in severe cases, hemodialysis, while being vigilant for withdrawal symptoms, especially in patients with chronic use, as abrupt discontinuation can lead to life-threatening complications 1.

Key Considerations

• Baclofen toxicity can occur due to overdose or impaired clearance, and symptoms can range from mild to severe, including drowsiness, confusion, respiratory depression, seizures, coma, and cardiovascular collapse.
• Treatment is primarily supportive, focusing on maintaining airway, breathing, and circulation, and flumazenil is not effective for baclofen toxicity as it works on GABA-B receptors rather than GABA-A.
• Patients with renal impairment are at higher risk for toxicity, and dosage adjustments are necessary in these populations.
• Recovery typically occurs within 24-48 hours after discontinuation in most cases, though prolonged symptoms may occur with sustained-release formulations or in patients with kidney dysfunction.

Management of Withdrawal Symptoms

• Abrupt discontinuation of baclofen after chronic use can cause withdrawal symptoms, including seizures and psychosis, and clinicians should be vigilant for these complications.
• Resuming the intrathecal infusion as soon as possible is the best management strategy for intrathecal baclofen withdrawal syndrome, and other supportive measures, such as high-dose benzodiazepine intravenous infusion or baclofen, may be lifesaving before intrathecal baclofen therapy can be resumed 1.

Important Precautions

• Personal protective equipment (PPE) should be used when performing procedures on patients with intrathecal pumps, and equipment should be protected from contamination using an appropriate cover.
• Required medications and equipment should be ready and transported in a fully covered plastic bag, with the bag and its medications handled with sterile gloves in a clean area.

From the FDA Drug Label

ADVERSE REACTIONS The most common is transient drowsiness (10% to 63%). In one controlled study of 175 patients, transient drowsiness was observed in 63% of those receiving baclofen compared to 36% of those in the placebo group. Other common adverse reactions are dizziness (5% to 15%), weakness (5% to 15%) and fatigue (2% to 4%) Others reported: Neuropsychiatric:Confusion (1% to 11%), headache (4% to 8%), insomnia (2% to 7%); and, rarely, euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, coordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizure 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

Baclofen toxicity can manifest as various adverse reactions, including:

• Neuropsychiatric symptoms: confusion, headache, insomnia, hallucinations, and epileptic seizure
• Withdrawal symptoms: increased muscle tone, tremor, jitteriness, and seizure, especially in neonates whose mothers were treated with oral baclofen throughout pregnancy
• Other symptoms: dizziness, weakness, fatigue, and rare instances of dyspnea, palpitation, chest pain, and syncope

It is essential to be cautious when using baclofen, especially in patients with impaired renal function, and to gradually reduce the dose when discontinuing the drug to avoid abrupt withdrawal symptoms 2 2.

From the Research

Baclofen Toxicity Overview

• Baclofen toxicity can result from intentional self-poisoning or accumulation of therapeutic doses in patients with impaired kidney function 3.
• Symptoms of baclofen poisoning can progress rapidly, and toxicity has been observed even with doses as low as 150 mg 4.

Clinical Presentation

• Patients with severe baclofen poisoning may present with deep coma, respiratory depression, seizures, and cardiovascular events such as mild hypo- or hypertension and bradycardia 4.
• Baclofen intoxication can mimic brain death, characterized by transient deep coma and absence of brainstem reflexes 5.
• Unique cardiovascular effects, including ST elevations on ECG and apical ballooning on echocardiogram, have been reported in cases of baclofen overdose 6.

Treatment

• Standard care for baclofen toxicity includes discontinuation of baclofen, respiratory support, and seizure treatment 3.
• The use of extracorporeal treatments (ECTRs) is controversial, but may be beneficial in reducing the duration of toxic encephalopathy in patients with impaired kidney function 3.
• Activated charcoal may be beneficial in reducing the final amount absorbed, especially if administered soon after ingestion 7.
• Gastric emptying is not recommended as a routine approach, but may be considered in certain circumstances, such as symptomatic patients presenting in the first hour after ingestion 7.

Management

• Patients with severe baclofen poisoning should be observed and treated in an intermediate- or intensive care unit 4.
• Maintenance of a protected airway and respiration is crucial in the management of baclofen toxicity 4.
• Early recognition and anticipation of complications, including haemodynamic volatility, are essential for effective management of baclofen overdose 6.