Which muscle relaxant, chlorzoxazone or tizanidine, has a lower risk of causing drowsiness?

Comparison of Chlorzoxazone vs Tizanidine for Drowsiness Risk

Tizanidine has a significantly higher risk of causing drowsiness compared to chlorzoxazone, making chlorzoxazone the preferred option when sedation is a concern.

Mechanism and Sedation Profile

Tizanidine

• Centrally acting α2-adrenergic agonist approved for spasticity
• Associated with significant central nervous system adverse effects, particularly sedation 1
• Causes substantial sedative and hypotensive effects, especially problematic in elderly patients 1
• Requires careful consideration in perioperative settings due to sedative properties

Chlorzoxazone

• Centrally acting muscle relaxant with different mechanism of action
• Associated with hepatotoxicity that is generally reversible and usually not serious 1
• Lower incidence of drowsiness compared to tizanidine
• Less central nervous system depression overall

Evidence for Drowsiness Risk

Skeletal muscle relaxants as a class are associated with central nervous system adverse events at a rate approximately twice that of placebo (RR 2.04, CI 1.23 to 3.37) 1. However, the specific risk profile differs between agents:

• Tizanidine is specifically noted for "significant sedative and hypotensive effects" 1
• Clinical guidelines recommend continuing tizanidine preoperatively due to risk of withdrawal, despite its sedative effects 1
• Chlorzoxazone, while still having CNS effects, has a more favorable drowsiness profile

Clinical Decision Algorithm

When choosing between these muscle relaxants with drowsiness as a concern:

1. First choice: Chlorzoxazone - when sedation must be minimized

   • Better option for patients who need to remain alert (e.g., those who drive, operate machinery)
   • Consider for daytime use when alertness is required

2. Use tizanidine with caution:

   • May be appropriate for nighttime dosing when sedation could be beneficial
   • Consider dose reduction in elderly patients or those sensitive to CNS effects
   • Monitor for excessive drowsiness, especially when combined with other CNS depressants

3. For both medications:

   • Start with lower doses to assess individual response
   • Avoid combination with other CNS depressants when possible
   • Counsel patients about potential drowsiness and precautions

Important Considerations

• Both medications can cause drowsiness, but tizanidine's α2-adrenergic mechanism produces more pronounced sedation
• Efficacy appears similar between muscle relaxants for acute low back pain 1
• The American College of Physicians/American Pain Society guidelines note that "there is no compelling evidence that skeletal muscle relaxants differ in efficacy," but acknowledge that "risk-benefit profiles could in theory vary substantially" 1
• Chlorzoxazone has been studied in combination with NSAIDs for back pain with good tolerability 2

Pitfalls to Avoid

• Don't assume all muscle relaxants have identical side effect profiles despite similar efficacy
• Avoid abrupt discontinuation of tizanidine in long-term users (can cause rebound hypertension and tachycardia) 1
• Be aware that both medications can cause liver enzyme elevations, though this is generally reversible
• Consider that individual patient response to sedative effects may vary considerably

When sedation is a primary concern, chlorzoxazone offers a more favorable profile than tizanidine while maintaining comparable efficacy for muscle spasm relief.