Why do Some Drugs Work in Some and not Others with Fibromyalgia?<\/h2>\n\n\n\n
Dr. Daniel Clauw highlights that drugs for fibromyalgia are not inherently less effective than those for other chronic pain conditions, rather, the challenge lies in the lack of a precision medicine approach.<\/p>\n\n\n\n
Fibromyalgia is a heterogeneous condition, meaning different patients have different brain chemistry and pain mechanisms. This variation leads to inconsistent drug responses across individuals.<\/p>\n\n\n\n
For example, pregabalin reduces glutamate in the brain, but only patients with elevated glutamate levels in pain-processing areas benefit.<\/p>\n\n\n\n
Current treatments like tricyclic antidepressants, gabapentinoids, and SNRIs offer modest effects overall, but results could improve if we could match treatments to specific patient subtypes.<\/p>\n\n\n\n
Emerging research using brain imaging and machine learning shows promise in predicting who will respond to which drug.<\/p>\n\n\n\n
Until precision tools become practical in clinical settings, fibromyalgia treatment will continue to involve trial and error.<\/p>\n\n\n\n
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- Fibromyalgia drug studies are similar to other chronic pain condition studies\n
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- A low to modest effect with tricyclic antidepressants (amitriptyline), gabapentinoids (gabapentin, pregabalin) and SNRIs (duloxetine)<\/li>\n<\/ul>\n<\/li>\n\n\n\n
- Because we do not have a \u201cprecision medicine\u201d approach\n
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- We would have greater success with drug treatments if we knew ahead of time who would respond well to which drug<\/li>\n<\/ul>\n<\/li>\n\n\n\n
- Patients with fibromyalgia are heterogeneous (people have different phenotypes, therefore respond to different drugs with different effects on pain pathways in the Central Nervous System (CNS).\n
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- But currently it is not practical to do phenotyping in fibromyalgia patients<\/li>\n\n\n\n
- Phenotyping in FM is empirical currently and lags behind study in other chronic pain conditions (eg. chronic low back pain).<\/li>\n<\/ul>\n<\/li>\n\n\n\n
- As as example;\n
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- if a patient has a high amount of glutamate in the insula part of the brain then they will respond to pregabalin because pregabalin works by lowering glutamate in the brain.<\/li>\n\n\n\n
- if a patient has normal amounts of glutamate in the insula then they will get no response to pregabalin.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n
![\"\"](\"https:\/\/fibrocanada.ca\/wp-content\/uploads\/2022\/01\/image.png\")
<\/figure>\n\n\n\nNeurotransmitters in the CNS that Influence Pain<\/u><\/h2>\n\n\n\n
There are two pathways that influence whether you feel pain<\/p>\n\n\n\n
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- The path that generally facilitates or increases transmission of pain\n
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- Fibromyalgia patients have increased levels of\n
- \n
- Glutamate<\/li>\n\n\n\n
- Substance P<\/li>\n\n\n\n
- Nerve Growth Factor (NGF)<\/li>\n<\/ul>\n<\/li>\n\n\n\n
- Serotonin types 2a and 3a<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n
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- The path that generally inhibits or decreases transmission of pain\n
- \n
- Fibromyalgia patients have decreased levels of\n
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- Norepinephrine<\/li>\n\n\n\n
- Serotonin types 1a and 1b<\/li>\n\n\n\n
- Dopamine<\/li>\n\n\n\n
- GABA (gamma-aminobutyric acid)<\/li>\n<\/ul>\n<\/li>\n\n\n\n
- Fibromyalgia patients have increased levels of\n
- \n
- Opioids<\/li>\n\n\n\n
- Cannabinoids work on this pathway<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n
REF: Nat Rev Rheumatol 2011;Jul 19;7(9):518-27.
JAMA 2014;Apr 16;311(15):1547-55.<\/p>\n\n\n\nWhat Drugs Work on Which Transmitters to Decrease Pain Transmission?<\/h2>\n\n\n\n
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- Decrease glutamate levels = gabapentin, pregabalin, ketamine, memantine<\/li>\n\n\n\n
- Affect serotonin 2a,3a = anti-migraine drugs (triptans), cyclobenzaprine<\/li>\n\n\n\n
- Increase norepinephrine-serotonin 1a,b and dopamine = tricyclics, SNRIs, Tramadol<\/li>\n\n\n\n
- Opioids = low dose naltrexone<\/li>\n\n\n\n
- GABA = gammahydroxybutyrate (sodium oxybate)<\/li>\n<\/ul>\n\n\n\n
New drug called NYX-2925 researched for Fibromyalgia<\/h2>\n\n\n\n
- \n
- NYX-2925 is a non-opioid small-molecule modulator of the N-methyl-D-aspartate receptor<\/li>\n\n\n\n
- Double-blind Phase 2 trial in 22 females treated with once daily dosing of placebo x 2 weeks then 20mg NYX x 2 weeks then 200mg NYX x 2 weeks<\/li>\n\n\n\n
- At beginning and during each second week of each treatment patients had functional MRIs and proton magnetic resonance spectroscopy completed<\/li>\n\n\n\n
- Results showed compared to placebo NYX-2925 20mg statistically decreased the glutamate levels and ratio of glutamate to creatine levels in pain areas of the brain associated with patient reported reductions in sensitivity to evoked pain<\/li>\n\n\n\n
- A decrease in connectivity between the different regions of the brain responsible for pain was statistically significant.<\/li>\n<\/ul>\n\n\n\n
REF: Harte SE et al. abstract from the 2019 American College of Rheumatology meeting<\/p>\n\n\n\n
Prediction of Drug Response in FM using Functional Neuroimaging Biomarkers and Support Vector Machine Algorithm<\/h2>\n\n\n\n
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- Used brain functional connectivity patterns (fMRI) to predict if patient would respond differentially to either pregabalin (13 patients) or milnacipran (15 patients)<\/li>\n\n\n\n
- Double-blind placebo-controlled crossover study<\/li>\n\n\n\n
- At least a 20% improvement in pain was classified as a responder to the drug<\/li>\n\n\n\n
- Brain connectivity results showed with 77% accuracy or 92% accuracy a pregabalin responder versus a milnacipran responder depending on the areas of the brain reviewed.<\/li>\n\n\n\n
- Conclusion: these findings show promise of machine learning in prediction of pain prognosis and treatment<\/li>\n<\/ul>\n\n\n\n
REF: Arthritis & Rheumatology 2021; doi 10.1002\/art.41781<\/p>\n\n\n\n
Summary:<\/h2>\n\n\n\n
- \n
- Drugs for fibromyalgia are not any less effective than drugs for other chronic pain conditions<\/li>\n\n\n\n
- Low to modest effect sizes seen with drugs studied<\/li>\n\n\n\n
- A precision medicine approach is necessary for all chronic pain conditions since there are different causes needing different treatments.<\/li>\n<\/ul>\n\n\n\n
Reported by Janice Sumpton October 29, 2021<\/em><\/p>\n\n\n\n\n- <\/ul>\n\n\n\n
- <\/ul>\n\n","protected":false},"excerpt":{"rendered":"
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- Fibromyalgia patients have decreased levels of\n
- The path that generally inhibits or decreases transmission of pain\n
- Fibromyalgia patients have increased levels of\n
- The path that generally facilitates or increases transmission of pain\n