Is Tizanidine (a muscle relaxant) effective for headache prevention?

Tizanidine for Headache Prevention

Tizanidine is not recommended as a first-line agent for headache prevention, as it lacks inclusion in established clinical guidelines that identify beta-blockers, tricyclic antidepressants, and anticonvulsants as evidence-based first-line therapies. 1

Guideline-Recommended First-Line Agents

The U.S. Headache Consortium and American College of Physicians have established clear evidence-based recommendations for migraine and chronic headache prevention that do not include tizanidine:

Beta-blockers (strongest evidence):

• Propranolol 80-240 mg/day has consistent evidence for efficacy 1, 2
• Timolol 20-30 mg/day has consistent evidence for efficacy 1, 2
• Propranolol is superior for migraine alone, while amitriptyline is better for mixed migraine and tension-type headache 1, 2

Tricyclic antidepressants:

• Amitriptyline 30-150 mg/day is the only antidepressant with consistent evidence supporting efficacy 1, 2
• Common side effects include drowsiness, weight gain, and anticholinergic symptoms 1, 2

Anticonvulsants:

• Divalproex sodium and sodium valproate have good evidence for efficacy 1, 2
• These may be especially useful in patients with prolonged or atypical migraine aura 1

Evidence for Tizanidine

While tizanidine is not mentioned in major headache prevention guidelines 1, 2, research studies have examined its potential role:

Positive findings from research trials:

• One double-blind, placebo-controlled trial (n=92 completers) showed tizanidine reduced headache index by 54% versus 19% for placebo (P=0.0025) in chronic daily headache 3
• Mean dose was 18 mg/day (range 2-24 mg) divided over three doses 3
• Improvements were seen in headache frequency, intensity, and duration 3
• An open-label study (n=31) showed 67% of patients improved more than 50% by weeks 9-12 4
• A small crossover trial (n=37) in women with chronic tension-type headache showed tizanidine was more effective than placebo 5

Mechanism of action:

• Tizanidine is an alpha-2 adrenergic agonist that inhibits norepinephrine release at the spinal cord and brain, with antinociceptive effects independent of the opioid system 3, 6
• It acts as a central muscle relaxant but may also have central effects on neuropeptides involved in migraine pathogenesis 6

Adverse effects:

• Somnolence (47%), dizziness (24%), dry mouth (23%), and asthenia (19%) were reported in clinical trials 3
• These side effects were usually mild to moderate 3, 4, 5
• Dropout rates due to adverse events did not differ significantly from placebo 3

Clinical Algorithm for Headache Prevention

Step 1: Start with guideline-recommended first-line agents:

• For migraine alone: Propranolol 80-240 mg/day 1, 2
• For mixed migraine and tension-type headache: Amitriptyline 30-150 mg/day 1, 2
• For patients with prolonged aura: Consider divalproex sodium 1

Step 2: Allow adequate trial period of 2-3 months at therapeutic dosing before declaring treatment failure 2

Step 3: If first-line agents fail or are contraindicated, consider alternative evidence-based options before tizanidine 1

Step 4: Tizanidine may be considered as an adjunctive or alternative agent only after failure of guideline-recommended therapies, particularly in chronic daily headache 3, 6

Critical Pitfalls to Avoid

• Do not use tizanidine as first-line therapy when evidence-based options with stronger guideline support are available and not contraindicated 1, 2
• The absence of tizanidine from major headache prevention guidelines (U.S. Headache Consortium, American College of Physicians) despite its research evidence suggests insufficient data to recommend it over established therapies 1
• Tizanidine's primary FDA indication is for spasticity management, not headache prevention 7
• Somnolence occurs in nearly half of patients, which may limit tolerability despite low dropout rates 3