Flexeril - SSRI Interaction Details (With Alternative Options)

In our latest question and answer, our pharmacist discusses the interaction between Flexeril and SSRIs and gives some alternative muscle relaxant options.


Good morning! I was wondering if there are any muscle relaxants or similar medications that can be used in conjunction with SSRIs. I am currently on Lexapro, and my doctor prescribed me Flexeril, but I have read that the two medications can interact. Are there safer alternatives that can help with muscular/nerve pain?

Asked by Erin On Mar 30, 2023

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Apr 04, 2023
Last updated Sep 26, 2023

Key points

  • Flexeril has a complex mechanism of action and can affect serotonin levels, potentially causing serotonin syndrome when taken with SSRIs like Lexapro.
  • Other muscle relaxants like methocarbamol, chlorzoxazone, and orphenadrine are less likely to interact with SSRIs than Flexeril because they do not significantly affect serotonin levels in the brain, making them potentially safer options.


Thanks for reaching out to us! This is a fantastic question and one I am happy to answer for you.

Flexeril With SSRI Interaction Details

You are correct that there is an interaction between Flexeril (cyclobenzaprine) and SSRIs, like Lexapro (escitalopram).

Flexeril is a muscle relaxer that has a complex mechanism of action. It is structurally similar to tricyclic antidepressants, which are known to affect serotonin levels.

Numerous studies have found that Flexeril likely works through several different actions, including central actions at the brain stem, and also via activity on several neurotransmitters, including norepinephrine, acetylcholine, and serotonin.

Since Flexeril can affect serotonin (it generally is reported to have a serotonin augmenting effect), it can interact with other medications that affect serotonin levels, such as SSRIs like Lexapro. When taken together, the risk of serotonin syndrome, a potentially life-threatening condition, may increase.

The prescribing information for Flexeril warns about this explicitly:

The development of a potentially life-threatening serotonin syndrome has been reported with cyclobenzaprine when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors.
Amrix (cyclobenzaprine) Prescribing Information

While there certainly are instances where the combination of Flexerial and an SSRI can be used and represents an acceptable therapy for some. they shouldn't be combined unless directed by your doctor.

What Muscle Relaxants Are Safer Than Flexeril With SSRIs?

Flexeril is one of the more commonly prescribed muscle relaxants, but there are other choices out there. Other prescription muscle relaxants include:

  • Robaxin (methocarbamol)
  • Soma (carisoprodol)
  • Baclofen
  • Chlorzoxazone
  • Skelaxin (metaxalone)
  • Orphenadrine
  • Tizanidine

Not all muscle relaxers affect serotonin as Flexeril does.

In fact, essentially every muscle relaxer on the list above, such as methocarbamol, chlorzoxazone, and orphenadrine, is less likely to interact with SSRIs than Flexeril because they do not significantly affect serotonin levels in the brain.

This makes them all potentially safer options for individuals who are taking SSRIs like Lexapro.

Methocarbamol is a muscle relaxer that works by blocking nerve impulses that are sent to the brain. It does not affect serotonin levels in the brain.

Chlorzoxazone is another muscle relaxer that works by blocking nerve impulses and likely does not affect serotonin.

Orphenadrine is a muscle relaxer that works primarily by working on motor centers in the brain and by blocking acetylcholine, a neurotransmitter that is involved in muscle contraction.

Tizanidine is thought to work primarily by affecting alpha-2 receptors.

Metaxalone is thought to work via the general CNS (central nervous system) depression.

Carisoprodol works by affecting communication between nerves in the central nervous system, but it does not directly affect serotonin levels in the brain.

Baclofen is structurally similar to the inhibitory neurotransmitter GABA and likely does not affect serotonin levels.

Out of all the muscle relaxants I've mentioned in this answer, only Flexeril has a warning about serotonin syndrome in the prescribing information for the drug.

Additional Thoughts From The Pharmacist

You mentioned your doctor prescribed you Flexeril as a muscle relaxant and for nerve pain. Based on how Flexeril works, this makes sense, since it likely affects norepinephrine, which is thought to be involved in causing nerve-type pain.

While some of the other options I talked about may help your pain, nerve pain can be difficult to treat and most muscle relaxants wouldn't be a great choice for that type of pain.

If you are looking to avoid drugs that significantly affect serotonin, some options include:

  • Gabapentin
  • Lyrica (pregabalin)
  • Capsaicin
  • Lidocaine
  • Anticonvulsants (e.g., carbamazepine, oxcarbazepine, topiratmate)

All of the above options do not affect serotonin to a significant degree.

Final Words

I hope you found this helpful!

I highly suggest talking to your doctor about what options are best for your particular medical situation. Thanks for contacting us!


  • Pharmacologic management of neuropathic pain: evidence-based recommendations, PubMed
  • Amrix Prescribing Information, AccessFDA
  • Soma Prescribing Information, AccessFDA
  • Zanaflex Prescribing Information, AccessFDA
  • Norflex Prescribing Information, AccessFDA

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at Hello@HelloPharmacist.com! You can also connect with Dr. Brian Staiger on LinkedIn.

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