What is the relationship between baclofen (GABA receptor agonist) and seizure risk?

From the Guidelines

Baclofen can cause seizures, particularly when abruptly discontinued after long-term use, and patients should be cautious when taking this medication, especially those with a history of epilepsy or seizures. According to the study published in Mayo Clinic Proceedings in 2021 1, significant withdrawal symptoms, including seizures, can occur when baclofen is discontinued abruptly, especially in patients who have been taking it long-term.

Key Points to Consider

• Baclofen withdrawal symptoms can be life-threatening, especially when the medication is stopped abruptly after long-term use
• Seizures are a potential symptom of baclofen withdrawal, along with visual and auditory hallucinations, anxiety, agitation, delirium, fever, tremors, and tachycardia
• Perioperative management of patients receiving intrathecal baclofen should be planned with input from a specialist in this area to minimize the risk of withdrawal symptoms, including seizures
• The risk of seizures is higher in patients who have been taking high doses of baclofen (>100mg daily) for extended periods

Recommendations for Use

• Patients with epilepsy or a history of seizures should use baclofen with caution, as it may lower the seizure threshold
• When starting baclofen, it's typically recommended to begin with a low dose (5-10mg three times daily) and gradually increase to minimize side effects, including seizure risk
• If a patient has been taking baclofen regularly, abrupt discontinuation should be avoided; instead, the medication should be tapered slowly over 1-2 weeks to prevent withdrawal symptoms, which can include seizures, hallucinations, and agitation
• Patients experiencing any unusual neurological symptoms while taking baclofen should seek immediate medical attention, as reported in the study 1

From the FDA Drug Label

In patients with epilepsy, the clinical state and electroencephalogram should be monitored at regular intervals, since deterioration in seizure control and EEG have been reported occasionally in patients taking baclofen. 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 Abrupt Drug Withdrawal:Hallucinations and seizures have occurred on abrupt withdrawal of baclofen

• Baclofen and seizures: The FDA drug label warns that baclofen may cause deterioration in seizure control in patients with epilepsy 2.
• Seizures as a withdrawal symptom: Seizures have also been reported as a withdrawal symptom in neonates whose mothers were treated with oral baclofen throughout pregnancy, as well as in patients who undergo abrupt withdrawal of baclofen 2 2.
• Clinical decision: Baclofen should be used with caution in patients with a history of seizures or epilepsy, and the clinical state and electroencephalogram should be monitored at regular intervals. Abrupt withdrawal of baclofen should be avoided to prevent seizures and other withdrawal symptoms.

From the Research

Baclofen and Seizures

• Baclofen is a medication used to treat muscle spasticity, and its relationship with seizures has been studied in various contexts.
• According to a study published in 1998 3, baclofen withdrawal syndrome can manifest with seizures, hallucinations, delirium, and high fever, especially when the dose is abruptly decreased or tapered rapidly.
• However, a study from 1983 4 found that baclofen does not appear to have a deleterious effect on seizure frequency in patients with epilepsy, and may even have an anticonvulsant effect in some cases.
• Another study from 2021 5 mentions that baclofen therapy is associated with potential complications, including life-threatening toxicity and withdrawal syndrome, but does not specifically discuss the relationship between baclofen and seizures.
• Other studies 6, 7 focus on the management of spasticity and the pharmacological treatments available, but do not provide direct evidence on the relationship between baclofen and seizures.

Baclofen Withdrawal and Seizures

• Baclofen withdrawal syndrome is a serious condition that can occur when the medication is suddenly stopped or tapered too quickly.
• Seizures are a potential symptom of baclofen withdrawal syndrome, as reported in the 1998 study 3.
• The management of baclofen withdrawal syndrome typically involves re-initiation or supplementation of baclofen dosing, as well as administration of other pharmacologic adjuncts to treat associated withdrawal symptoms 5.