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06. Pharmacologic Therapies for Fibromyalgia

Published on July 1, 2023 Certification expiration date: July 1, 2026

Daniel J. Clauw, M.D.

Professor of anesthesiology & Psychiatry at the University of Michigan - Georgetown University

Key Points

The recommended pharmacologic therapies for nociplastic pain include:
-Tricyclic drugs.
-SNRIs.
-Gabapentinoids.

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Pharmacologic therapies for fibromyalgia or centralized pain.

Pharmacologic Therapies for Fibromyalgia Slide 1 of 13

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The three classes of drugs that seem to be most effective are tricyclic drugs which would include amitriptyline and cyclobenzaprine. A low dose of cyclobenzaprine is one of my favorite drugs for fibromyalgia, 2.5, 5 mg, 7.5 mg of cyclobenzaprine a couple of hours before bedtime can be really helpful.

References:

Clauw D. J. (2014). Fibromyalgia: A clinical review. JAMA, 311(15), 1547–1555.

Pharmacologic Therapies for Fibromyalgia Slide 2 of 13

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The serotonin-norepinephrine reuptake inhibitors, the ones that are more noradrenergic like milnacipran and duloxetine seem to be more effective.

References:

Clauw D. J. (2014). Fibromyalgia: A clinical review. JAMA, 311(15), 1547–1555.

Pharmacologic Therapies for Fibromyalgia Slide 3 of 13

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And then the gabapentinoids, such as pregabalin and gabapentin, these drugs can be quite helpful. They're probably working at least in part by helping improve sleep. And one of the things you should know about these drugs is you often can get by just using a single nighttime dose of these drugs rather than giving them two to three times a day and often that will have the same beneficial effect with less of the side effects we see with other drugs.

References:

Clauw D. J. (2014). Fibromyalgia: A clinical review. JAMA, 311(15), 1547–1555.

Pharmacologic Therapies for Fibromyalgia Slide 4 of 13

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Other drugs for fibromyalgia include tramadol, older less selective SSRIs, gamma-hydroxybutyrate, low-dose naltrexone.

References:

Clauw D. J. (2014). Fibromyalgia: A clinical review. JAMA, 311(15), 1547–1555.

Pharmacologic Therapies for Fibromyalgia Slide 5 of 13

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The body's own endogenous opioid system or internal opioid system is hyperactive in people with fibromyalgia. We should be blocking the endogenous opioid system in people with conditions like fibromyalgia, not giving them opioids.

References:

Clauw D. J. (2014). Fibromyalgia: A clinical review. JAMA, 311(15), 1547–1555.

Pharmacologic Therapies for Fibromyalgia Slide 6 of 13

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We actually might likely be making conditions like fibromyalgia worse by giving someone an opioid. We've historically focused on the fact that opioids don't make people better but there's a lot of evidence and continuing to emerge that a lot of individuals with chronic pain that are given opioids that develop opioid-induced hyperalgesia and their pain is literally made worse by that class of drugs not, simply not made better.

References:

Clauw D. J. (2014). Fibromyalgia: A clinical review. JAMA, 311(15), 1547–1555.

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And we actually know that a lot of the neurotransmitters that control pain and sensory transmission are out of balance in conditions like fibromyalgia. Some of the neurotransmitters that increase pain and sensory sensitivity like glutamate, substance P, and nerve growth factor are too high in conditions like fibromyalgia. Other neurotransmitters that decrease pain and sensory sensitivity like norepinephrine, serotonin, GABA are too low.

References:

Clauw D. J. (2014). Fibromyalgia: A clinical review. JAMA, 311(15), 1547–1555.

Pharmacologic Therapies for Fibromyalgia Slide 8 of 13

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Why it's really complicated to give someone an opioid to treat chronic pain. The longer people take opioids, the more the body adjusts to those opioids. People become tolerant to the opioids. They develop opioid-induced hyperalgesia. And it's almost impossible to get a lot of these patients off opioids, not because they're working well but because they become dependent on the opioid and it's permanently changed the way their endogenous opioid system works.

References:

Clauw, D. (2017). Hijacking the endogenous opioid system to treat pain: Who thought it would be so complicated? Pain, 158(12), 2283-2284.

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This study is a particularly cautionary tale. We did PET with carfentanil which is a highly potent opioid at the same time as we did functional MRI in people with fibromyalgia. And it looked as though these individuals with fibromyalgia are overproducing endogenous opioids like endorphins and enkephalins in brain regions and that might be driving the worsening of fibromyalgia.

References:

Schrepf, A., Harper, D. E., Harte, S. E., Wang, H., Ichesco, E., Hampson, J. P., Zubieta, J. K., Clauw, D. J., & Harris, R. E. (2016). Endogenous opioidergic dysregulation of pain in fibromyalgia: A PET and fMRI study. Pain, 157(10), 2217–2225.

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You should be particularly careful with giving individuals with fibromyalgia an opioid because, again, you may not just not make it better. You may make it worse.

References:

Schrepf, A., Harper, D. E., Harte, S. E., Wang, H., Ichesco, E., Hampson, J. P., Zubieta, J. K., Clauw, D. J., & Harris, R. E. (2016). Endogenous opioidergic dysregulation of pain in fibromyalgia: A PET and fMRI study. Pain, 157(10), 2217–2225.

Pharmacologic Therapies for Fibromyalgia Slide 11 of 13

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The drugs you should be using for nociplastic pain right now are low doses of tricyclic drugs given at bedtime, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids.

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Next Section

07. Fibromyalgia and Medical Cannabis

Learning Objectives:

After completing this activity, the learner will be able to:

Delve into the pain mechanisms and appreciate their clinical relevance.
Learn the essential steps for recognizing and accurately diagnosing patients with fibromyalgia.
Execute impactful pharmacologic and nonpharmacologic interventions for chronic pain management.

Original Release Date: July 1, 2023

Review and Re-release Date: March 1, 2024

Expiration Date: July 1, 2026

Expert: Daniel Clauw, M.D.

Medical Editor: Paz Badía, M.D.

Relevant Financial Disclosures:

Daniel Clauw declares the following interests:

- Pfizer: Consultant
- Tonix: Consultant, research support
- Virios: Consultant

All of the relevant financial relationships listed above have been mitigated by Medical Academy and the Psychopharmacology Institute.

Contact Information: For questions regarding the content or access to this activity, contact us at support@psychopharmacologyinstitute.com

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