Flexeril (Cyclobenzaprine) For Migraines?

In our latest question and answer, the pharmacist discusses the use of Flexeril (cyclobenzaprine) for migraines.

Jul 29, 2018

Jen asked

My mother’s doctor (pain mgmt) told her that Flexeril would also help her headaches because it has a 'Triptan' in it. I told her this was ridiculous, that Flexeril is NOT a triptan drug, and she does not believe me swearing that the doctor says it is. Please settle this.

Answer

You are correct in saying that Flexeril (cyclobenzaprine) is not a 'Triptan' drug. Flexeril is a skeletal muscle relaxant drug while 'Triptans' are a class of medications (containing several) used for the treatment of migraine headaches. 

There may be some confusion here in terms of what Flexeril is. Flexeril is only indicated for the treatment of muscle spasm. It is rarely even used 'off-label' for other indications, but it has been used for fibromyalgia.


However, there is some thought Flexeril may help prevent chronic migraines based on its mechanism of action. In fact, there were clinical trials investigating this: Efficacy and Safety of Cyclobenzaprine Hydrochloride Extended Release for the Treatment of Chronic Migraine. There are no current clinical trials underway.

How Does Flexeril Work?

Cyclobenzaprine is a skeletal muscle relaxant, indicated for the relief of muscle spasm associated with musculoskeletal conditions. It is chemically related to a class of medications known as tricyclic antidepressants. Although it does not possess antidepressant activity, is does share some pharmacologic effects.

The exact mechanism of action of Flexeril isn't well known, but it does appear to have a variety of effects, including:

  • Action primarily within the central nervous system at brain stem
  • Anticholinergic activity
  • Increase in norepinephrine
  • Augmentation of serotonin

The serotonin effects of Flexeril (cyclobenzaprine) may be the reason why your mothers doctor likened it to "Triptan" drugs.

Triptan drugs (which include Imitrex, Relpax and Maxalt) stimulate serotonin receptors, which is why it helps with the pain from migraines. Serotonin stimulation has a variety of effects, including:

  • Inhibition of vasodilation (i.e. vasoconstrictor properties)
  • Inhibition of inflammation
  • Inhibit nociceptive neurotransmission (i.e. decrease pain signals)

Again, the full effects on serotonin by Flexeril aren't known. Some studies report that it can increase, or at least, augment the actions of serotonin, which is why it has been linked to drug interactions causing serotonin syndrome when used with other serotonergic drugs. Other studies however, report that it antagonizes certain serotonin receptors in the spinal cord.

Depending on the cause of migraines in a certain individuals, a reduction in muscle tone or spasticity by Flexeril may certainly help relieve migraines or prevent them from occurring as often. However, as discussed above, this is not an FDA approved indication for Flexeril.

The key takeaways are:

  • Flexeril (cyclobenzaprine) is not a 'Triptan' drug and is not structurally related to them.
  • Triptan drugs are a specific class of medication used for migraine headaches.
  • Flexeril is not indicated for the treatment of migraines.
  • Flexeril may share some similar properties to Triptan drugs (e.g. serotonin effects), but the exact mechanism behind this isn't well known.

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