Drugs for Spasticity

Drugs for spasticity reduce velocity-dependent increase in muscle tone caused by upper motor neurone lesions in multiple sclerosis, spinal cord injury, stroke, cerebral palsy and brain injury. Treatment aims to improve comfort, care and function, not to abolish tone that supports standing.

Classification. GABA-B agonists (baclofen), alpha2 agonists (tizanidine), peripheral relaxants (dantrolene), benzodiazepines (diazepam), botulinum toxin, and cannabinoids.

• Baclofen 5 mg three times daily, increased by 5 mg every 3 days to 30 to 80 mg daily; maximum 100 mg daily. Intrathecal after a test dose of 50 microgram, maintenance 300 to 800 microgram daily.
• Tizanidine 2 mg at night, increased to 4 mg three times daily; maximum 36 mg daily.
• Dantrolene 25 mg daily, increased weekly to 100 mg four times daily; maximum 400 mg daily.
• Diazepam 2 to 10 mg at night.
• Botulinum toxin A injected into affected muscles, with dose set by muscle; total maximum 400 units.

Differences. Baclofen is first-line for generalised spasticity. Tizanidine causes less weakness but more sedation. Botulinum toxin suits focal spasticity. Dantrolene is the only drug acting on muscle but is hepatotoxic.

• Before drugs: remove triggers (urinary infection, constipation, pressure sores, pain, tight clothing) and give physiotherapy and stretching.
• Generalised spasticity: baclofen; add tizanidine or a benzodiazepine at night.
• Focal spasticity: botulinum toxin A.
• Severe disabling spasticity: intrathecal baclofen in specialist centres.
• Baclofen withdrawal: never stop abruptly; abrupt cessation or pump failure causes rebound spasticity, seizures, hallucinations, hyperthermia and rhabdomyolysis. Restart oral baclofen, give benzodiazepines, and seek intensive care for pump failure.

Selection. Start low; tone may be useful for transfers and standing.

Contraindications. Tizanidine with ciprofloxacin or fluvoxamine. Dantrolene in liver disease. Baclofen in peptic ulcer (caution) and seizure disorders (caution).

Adverse effects. Drowsiness, weakness, dizziness, confusion, hypotension, urinary retention, constipation. Hepatotoxicity (tizanidine, dantrolene). Baclofen overdose causes coma, respiratory depression and seizures.

Interactions. Additive sedation with alcohol, opioids and benzodiazepines. Tizanidine levels rise sharply with CYP1A2 inhibitors.

Special groups.

• Kidney impairment (baclofen): neurotoxicity occurs at usual doses; reduce the dose by one third at creatinine clearance 50 to 80 mL/min, by half at 30 to 50 mL/min, and by two thirds below 30 mL/min; avoid in dialysis.
• Pregnancy: limited data; avoid unless needed.
• Breastfeeding: baclofen acceptable in small doses.
• Children: weight-based specialist dosing.
• Older adults: lower doses; confusion and falls.
• Liver impairment: avoid dantrolene; reduce tizanidine.

Monitoring. Tone, function, sedation, mood, bladder emptying, and liver enzymes for tizanidine and dantrolene (baseline, then monthly for 3 months).

Referral and escalation. Sudden worsening of tone (look for infection, constipation, a pressure sore), symptoms of baclofen withdrawal, or need for intrathecal therapy.