What is the recommended dose of baclofen (GABA receptor agonist) for treating spasticity?

Baclofen Dosing for Spasticity

Oral Baclofen Dosing

For spasticity of spinal origin, start baclofen at 5 mg three times daily in older adults, with gradual titration to an effective dose that rarely exceeds 30-40 mg per day in elderly patients. 1

Initial Dosing Strategy

• Start with 5 mg up to three times daily for older adults or those at higher risk of adverse effects 1
• Monitor closely for muscle weakness, urinary dysfunction, cognitive effects, and sedation during initiation 1
• The standard starting approach involves low-dose initiation with incremental increases to minimize side effects 2

Dose Titration and Maintenance

• Titrate gradually upward from the starting dose, as most adverse effects are dose-related and appear at doses >60 mg/day 2
• The effective dose range in clinical practice is typically 10-80 mg daily in divided doses, though the FDA-approved maximum is 80 mg/day 2
• Older adults rarely tolerate doses greater than 30-40 mg per day and should remain at the lower end of the dosing spectrum 1
• In open-label studies, oral baclofen improved spasticity in 70-87% of patients and spasms in 75-96% of patients 2

Critical Dosing Considerations

• Adverse effects occur in 10-75% of patients and include sedation, excessive weakness, dizziness, mental confusion, and somnolence 2, 3
• The incidence of treatment discontinuation due to intolerable adverse effects ranges from 4-27% 3
• Never discontinue baclofen abruptly - taper gradually to avoid withdrawal symptoms including seizures, psychic symptoms, and hyperthermia 1, 2

Special Populations

• Patients with renal disease carry unnecessarily high risk with baclofen administration due to impaired clearance 2
• In patients on stable dosing regimens, baclofen blood levels may rise gradually over time due to impaired renal clearance, particularly in those with neurogenic bladder 4
• Patients with brain damage and the elderly are at higher risk for seizures, psychic symptoms, and hyperthermia even when not related to withdrawal 2

Modified-Release Formulations

• Once-daily baclofen sustained release (SR) or gastric retentive system (GRS) formulations at the same total daily dose as immediate-release baclofen are efficacious alternatives 5
• These formulations provide uniform effect throughout the day and are associated with significantly decreased sedation scores compared to immediate-release formulations 5
• Modified-release formulations improve medication compliance by eliminating the need for three-times-daily dosing 5

Intrathecal Baclofen Therapy

Indications

Intrathecal baclofen is indicated for patients with spasticity of spinal origin unresponsive to maximum doses of oral baclofen, tizanidine, and/or dantrolene, or who experience intolerable side effects from oral medications. 1, 3

Screening and Initiation

• Candidates must have no contraindications to intrathecal catheter insertion (anticoagulant therapy, coagulopathy, local/systemic infection, spinal anatomical abnormality) 3
• Start with an effective bolus screening dose to determine response before pump implantation 6
• The starting daily dose should be twice the effective bolus screening dose, or equal to the screening dose if the patient had a prolonged response (>8 hours) or negative reactions 6
• Initiate with the 500 mcg/mL concentration and begin pump fill and drug delivery intraoperatively with monitoring for at least 8 hours 6

Dose Titration

• For adults with spinal-origin spasticity: increase daily dose by 10-30% once every 24 hours 6
• For adults with cerebral-origin spasticity: increase daily dose by 5-15% once every 24 hours 6
• For children: increase daily dose by 5-15% once every 24 hours 6
• Assessment should occur within 24 hours of each dose change 6

Clinical Outcomes

• >80% of patients experience improvement in muscle tone and >65% show improvement in spasms with continuous intrathecal baclofen infusion 2
• Intrathecal administration uses concentrations less than one-hundredth of oral doses while achieving higher CSF levels 3
• Central side effects (drowsiness, confusion) are minimized compared to oral administration 3

Critical Safety Warnings

• The main risks are overdose and withdrawal, with withdrawal being more dangerous due to severe clinical effects and possibility of death 2
• Overdose primarily occurs from test doses or human error during pump refill/programming 2
• Withdrawal most commonly results from delivery system problems 2
• Oral antispasmodics should be weaned one drug at a time, beginning with oral baclofen, after intrathecal therapy begins 6

Alternative Use: Alcohol Abstinence

• Baclofen at 10 mg three times daily (30 mg/day total) for 12 weeks effectively maintained abstinence in patients with liver cirrhosis and alcohol use disorder 1
• This represents the only pharmacotherapy for alcohol use disorder tested in patients with advanced liver disease 1
• Patients with hepatic encephalopathy should be excluded as baclofen may impair mentation 1