Skeletal Muscle Relaxants

Skeletal muscle relaxants reduce muscle spasm and tone in painful musculoskeletal conditions through central nervous system depression or direct muscle action. Evidence for most is limited, and benefit is short term.

Classification. Centrally acting relaxants (cyclobenzaprine, methocarbamol, orphenadrine, tizanidine, chlorzoxazone, thiocolchicoside, eperisone), benzodiazepines (diazepam), and the direct-acting relaxant dantrolene.

Pharmacokinetics. Mostly hepatic metabolism with half lives of 1 to 8 hours. Tizanidine is cleared by CYP1A2.

• Cyclobenzaprine 5 to 10 mg three times daily; maximum 30 mg daily; 2 to 3 weeks only.
• Methocarbamol 1.5 g four times daily for 2 to 3 days, then 1 g four times daily.
• Orphenadrine 100 mg twice daily.
• Tizanidine 2 mg at night or three times daily, increased to 4 mg three times daily.
• Chlorzoxazone 250 to 500 mg three to four times daily.
• Thiocolchicoside 4 to 8 mg twice daily for up to 7 days.
• Eperisone 50 mg three times daily.
• Diazepam 2 to 5 mg three times daily for up to 1 week.
• Dantrolene 25 mg daily, increased to 100 mg four times daily; maximum 400 mg daily.

Differences. Diazepam adds dependence risk. Chlorzoxazone and dantrolene can cause hepatotoxicity. Thiocolchicoside has genotoxic concerns, so duration is limited.

• Acute low back pain and muscle spasm: short course alongside NSAIDs, heat and early movement.
• Chronic back pain: not advised.
• Nocturnal cramps: stretching; no drug has strong support.
• Tetanus, neuroleptic malignant syndrome, malignant hyperthermia: specialist use of diazepam or dantrolene (malignant hyperthermia 2.5 mg/kg intravenously, repeated to effect).

Selection. Use the lowest dose for the shortest time; sedation is the main limit.

Contraindications. Myasthenia gravis, severe liver disease (dantrolene, chlorzoxazone, tizanidine), respiratory depression, sleep apnoea, and pregnancy (thiocolchicoside).

Adverse effects. Drowsiness, dizziness, dry mouth, hypotension, confusion, falls. Hepatotoxicity (chlorzoxazone, dantrolene, tizanidine), seizures with thiocolchicoside, anticholinergic effects (cyclobenzaprine, orphenadrine), serotonin syndrome with cyclobenzaprine.

Interactions. Ciprofloxacin and fluvoxamine are contraindicated with tizanidine. Additive sedation with alcohol, opioids and benzodiazepines. Cyclobenzaprine with MAO inhibitors.

Special groups.

• Pregnancy: avoid.
• Breastfeeding: avoid.
• Children: avoid except specialist use.
• Older adults: avoid cyclobenzaprine, orphenadrine and diazepam.
• Kidney impairment: reduce tizanidine in creatinine clearance under 25 mL/min.
• Liver impairment: avoid.

Monitoring. Sedation, falls, liver enzymes with prolonged use.

Referral and escalation. Back pain with neurological deficit, bladder or bowel disturbance, fever or weight loss needs investigation rather than relaxants.