Is Flexeril (cyclobenzaprine) effective for temporary relief of restless leg syndrome?

Flexeril (Cyclobenzaprine) for Restless Leg Syndrome

Flexeril (cyclobenzaprine) is not recommended for the treatment of restless leg syndrome (RLS), as it is not included in any current treatment guidelines and may potentially worsen symptoms due to its antihistaminergic properties. 1, 2

First-Line Treatment Options for RLS

• Alpha-2-delta ligands are strongly recommended as first-line therapy for RLS by the American Academy of Sleep Medicine due to their efficacy and lower risk of augmentation compared to dopaminergic agents 2

  • Gabapentin is strongly recommended with moderate certainty of evidence 2
  • Pregabalin is strongly recommended with moderate certainty of evidence 2
  • Gabapentin enacarbil (extended-release) is strongly recommended with moderate certainty of evidence 2

• Iron supplementation should be considered if serum ferritin ≤75 ng/mL or transferrin saturation <20%, as iron deficiency can exacerbate RLS symptoms 1, 2

  • Oral ferrous sulfate is conditionally recommended for patients with appropriate iron parameters 2
  • IV ferric carboxymaltose is strongly recommended for patients who don't respond to oral therapy 2

Medications to Avoid in RLS

• The American Academy of Sleep Medicine recommends against using antihistaminergic medications in RLS patients as they may worsen symptoms 2
• Cyclobenzaprine (Flexeril) has antihistaminergic properties that could potentially exacerbate RLS symptoms rather than relieve them 2
• The American Academy of Sleep Medicine specifically recommends against several medications for RLS, including clonazepam, valproic acid, and other medications not specifically studied for RLS 2

Second-Line Treatment Options

• For patients with moderate to severe symptoms who don't respond to first-line treatments:
  • Opioids (extended-release oxycodone and others) are conditionally recommended, particularly for refractory cases 2, 3
  • Dopaminergic agents (with caution due to augmentation risk):
    • The American Academy of Sleep Medicine suggests against standard use of dopamine agonists including levodopa, pramipexole, ropinirole, and rotigotine due to risk of augmentation 2, 4
    • If used, they should be started at low doses and monitored closely 4

Non-Pharmacological Approaches

• The American Academy of Sleep Medicine recommends implementing non-pharmacological approaches including 1, 2:
  • Moderate exercise
  • Smoking cessation
  • Alcohol avoidance
  • Caffeine reduction or elimination
  • Discontinuation of medications that may worsen RLS
• Bilateral high-frequency peroneal nerve stimulation is conditionally recommended as a non-pharmacological option 2

Treatment Algorithm for RLS

1. Assess and address iron status (supplement if ferritin ≤75 ng/mL or transferrin saturation <20%) 1, 2
2. Identify and discontinue medications that may exacerbate RLS symptoms, including antihistamines like cyclobenzaprine 1, 2
3. Implement non-pharmacological approaches 1, 2
4. For pharmacological treatment, start with alpha-2-delta ligands (gabapentin, pregabalin, or gabapentin enacarbil) 2
5. For refractory cases, consider opioids 2, 3

Caution

• Cyclobenzaprine (Flexeril) is a muscle relaxant with antihistaminergic properties that may potentially worsen RLS symptoms 2
• The American Academy of Sleep Medicine specifically recommends against using medications with antihistaminergic properties in RLS patients 2
• No clinical studies support the use of cyclobenzaprine for RLS treatment 5, 3