In which patients is baclofen (GABA receptor agonist) contraindicated?

Baclofen Contraindications

Baclofen is absolutely contraindicated in patients with severely impaired renal function (eGFR <30 mL/min/1.73m²) and those on renal replacement therapy, and should be avoided in patients with rheumatic skeletal muscle spasm, stroke, cerebral palsy, and Parkinson's disease where efficacy is not established. 1, 2

Absolute Contraindications

Severe Renal Impairment

• Patients with eGFR <30 mL/min/1.73m² or on dialysis should not receive baclofen due to extremely high risk of neurotoxicity, even at low doses 2
• Baclofen is primarily excreted unchanged through the kidneys, leading to dangerous accumulation in renal failure 1, 3
• Toxicity develops rapidly—often within 48 hours of initiating even low-dose therapy (as little as 1 mg/kg total daily dose in children) 4, 5
• Clinical manifestations include encephalopathy, altered consciousness, hypotonia, areflexia, respiratory depression, seizures, and hemodynamic instability 3, 4, 2

Non-Indicated Conditions (FDA Label)

• Rheumatic skeletal muscle spasm—baclofen is not indicated and should not be used 1
• Stroke patients—baclofen has not significantly benefited these patients and they show poor tolerability 1
• Cerebral palsy—efficacy not established 1
• Parkinson's disease—efficacy not established 1

Relative Contraindications and High-Risk Populations

Hepatic Dysfunction

• Patients with significant hepatic impairment are at increased risk for CNS effects and should avoid baclofen 6, 7
• The European Association for the Study of the Liver notes baclofen may be used cautiously in alcohol-related liver disease for alcohol use disorder treatment, but this is a specialized indication 8, 9

Elderly Patients

• Higher risk for CNS side effects including drowsiness, dizziness, sedation, and hypotensive effects 7
• The American Geriatrics Society recommends considering alternative therapies before initiating baclofen in elderly patients 7
• When used, start at the lowest dose (5 mg/day) and titrate slowly 6

Respiratory Compromise

• Baclofen can cause respiratory depression as a manifestation of CNS toxicity, particularly in overdose 6
• Use extreme caution in patients with compromised respiratory function, similar to contraindications for beta-blockers in reactive airway disease and COPD 8, 6
• Baclofen may worsen obstructive sleep apnea by promoting upper airway collapse during sleep 6

Pregnancy

• Baclofen increases the incidence of omphaloceles (ventral hernias) in animal studies at 13 times the maximum human dose 1
• Neonatal withdrawal symptoms (increased muscle tone, tremor, jitteriness, seizures) occur in infants whose mothers received baclofen throughout pregnancy 1
• If continued during pregnancy, gradually reduce and discontinue before delivery; if not feasible, warn parents/caregivers of potential neonatal withdrawal 1

Critical Safety Warnings

Abrupt Discontinuation

• Never abruptly discontinue baclofen in any patient on chronic therapy—withdrawal can be life-threatening 6, 7, 1
• Withdrawal symptoms include hallucinations, seizures, high fever, altered mental status, rebound spasticity, muscle rigidity, tachycardia, and potentially death 6, 7, 1
• This is particularly catastrophic with intrathecal baclofen, where withdrawal can cause multiorgan failure 7
• Taper slowly over weeks if discontinuation is necessary 6

Drug Interactions

• Baclofen increases sedation risk when combined with opioids or other CNS depressants 7
• Avoid concurrent use with benzodiazepines during stroke recovery due to deleterious effects 6
• The combination with other CNS depressants requires extreme caution due to additive sedation 6, 7

Common Pitfalls to Avoid

• Do not prescribe baclofen for any dose in patients with severely impaired renal function—even 5 mg can cause toxicity 4, 2
• Do not use baclofen beyond 10-14 days for alcohol withdrawal syndrome due to abuse potential 8
• Do not confuse short-term AWS treatment with long-term alcohol use disorder maintenance therapy—these are distinct indications 9
• Do not use baclofen as first-line for focal spasticity—botulinum toxin is more effective and better tolerated 6
• Recognize that abdominal pain is a common presenting feature of baclofen toxicity in renal failure patients, in addition to altered consciousness 4