Do orphenadrine or methocarbamol lower the seizure threshold?

Orphenadrine vs. Methocarbamol and Seizure Threshold

Neither orphenadrine nor methocarbamol are specifically associated with lowering the seizure threshold, though orphenadrine carries a slightly higher theoretical risk due to its anticholinergic properties.

Orphenadrine and Seizure Risk

• Orphenadrine is a centrally acting skeletal muscle relaxant structurally similar to diphenhydramine with anticholinergic properties 1
• While not explicitly listed as lowering seizure threshold in guidelines, orphenadrine's anticholinergic effects (confusion, anxiety, tremors) suggest a theoretical potential to affect CNS excitability 1
• Orphenadrine should be used with caution in patients with:
  • Cardiac conditions (tachycardia, cardiac decompensation, coronary insufficiency, arrhythmias) 1
  • Elderly patients 1
  • Patients with myasthenia gravis 1
• No specific warnings about seizure threshold are mentioned in the Mayo Clinic Proceedings consensus guidelines 1

Methocarbamol and Seizure Risk

• Methocarbamol is an oral or intravenous centrally acting skeletal muscle relaxant and sedative 1
• The FDA drug label for methocarbamol mentions seizures only in the context of overdose, not as a risk at therapeutic doses 2
• Overdose symptoms include "nausea, drowsiness, blurred vision, hypotension, seizures, and coma" 2
• Methocarbamol's adverse effects primarily include drowsiness, dizziness, and cardiovascular effects (bradycardia and hypotension) 1
• No specific warnings about lowering seizure threshold at therapeutic doses are mentioned in guidelines 1

Comparison of Seizure Risk

• Neither drug is specifically identified as having high seizure risk in major guidelines 1
• In general, psychotropic drugs that lower seizure threshold do so in a dose-dependent manner 3
• Risk factors for drug-induced seizures include:
  • History of epilepsy or previous seizures 4, 3
  • Cancer 4
  • Blood-brain barrier dysfunction 4
  • Neurological diseases 4
  • Mental disorders 4
  • Very young or elderly age 4
  • Liver or kidney disease 4
  • Polypharmacy 4

Clinical Implications

• For patients with epilepsy or seizure risk factors, consider:
  • Avoiding high doses of either medication 4, 3
  • Starting with lower doses and titrating slowly 3
  • Monitoring for signs of increased CNS excitability 4
• In patients with 22q11.2 deletion syndrome who have a lower seizure threshold, caution should be exercised with all centrally acting medications 1
• For patients requiring muscle relaxants who have seizure disorders, methocarbamol may be slightly preferred over orphenadrine based on mechanism of action and side effect profile 1, 2

Perioperative Considerations

• Both medications are recommended to be held on the day of surgical procedures according to the Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement 1
• This recommendation is based on sedative properties rather than seizure risk 1

Alternative Muscle Relaxants

• For patients with seizure disorders requiring muscle relaxants, consider:
  • Tizanidine (alpha-2 adrenergic agonist) - not known to lower seizure threshold
  • Baclofen (GABA-B receptor agonist) - may have anticonvulsant properties at therapeutic doses
• Avoid cyclobenzaprine in patients taking monoamine oxidase inhibitors due to serotonin syndrome risk 1
• Tramadol should be avoided in patients with seizure history as it explicitly lowers seizure threshold 1