Current and Emerging Pharmacotherapy for Fibromyalgia
Open accessAbstract
Introduction . Fibromyalgia syndrome (FMS) is a pain disorder with an estimated prevalence of 1–5%. It is associated with a variety of somatic and psychological disorders. Its exact pathogenesis is still unclear but is involved with neural oversensitization and decreased conditioned pain modulation (CPM), combined with cognitive dysfunction, memory impairment, and altered information processing. Connectivity between brain areas involved in pain processing, alertness, and cognition is increased in the syndrome, making its pharmacologic therapy complex. Only three drugs, pregabalin, duloxetine, and milnacipran are currently FDA-approved for FM treatment, but many other agents have been tested over the years, with varying efficacy. Areas Covered . The purpose of this review is to summarize current clinical experience with different pharmacologic treatments used for fibromyalgia and introduce future perspectives in developing therapies. Expert Opinion . Future insights into the fields of cannabinoid and opioid research, as well as an integrative approach towards the incorporation of genetics and functional imaging combined with additional fields of research relevant towards the study of complex CNS disorders, are likely to lead to new developments of novel tailor-made treatments for FMS patients.
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The model is compliant with the generally poor efficacies of drugs currently used in FM therapy, but also with the relatively higher efficacy of gabapentinoids.
“Fourth, it is compliant with the generally poor efficacies of drugs currently used in FM therapy, but also with the relatively higher efficacy of gabapentinoids [7,140].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [140]
The Introduction describes pharmacological treatment for fibromyalgia as having “rather modest rates of success.” Section 3.6 reports benefits from pregabalin and gabapentin for several symptoms, but does not establish that gabapentinoids are more effective than other drugs used for fibromyalgia. The relative-efficacy comparison is therefore unsupported by this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBoth pharmacological and nonpharmacological therapies for FM are generally disappointing, providing very limited benefit to FM patients.
“For what concerns FM, both pharmacological and nonpharmacological therapies are generally disappointing, providing very limited benefit to FM patients [4,140,155,156].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [140]
The Introduction says pharmacological treatment has had generally modest success, supporting that part of the claim. It recommends combining medication with nonpharmacological approaches, but does not say those approaches are generally disappointing or provide very limited benefit. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredEvidence exists that several pharmacological options (antidepressants, anticonvulsants) and nonpharmacological treatments (CBT) are used for fibromyalgia.
“اکنون شواهدی وجود دارد که برای درمان فیبرومیالژیا از چندین گزینه دارویی مثل داروهای ضدافسردگی و ضدتشنج و درمان غیردارویی مثل درمان شناختی رفتاری استفاده میشود ] 8 [ .”
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Cites
Psychosomatic medicine in Germany: more timely than ever
Zipfel, S., Herzog, W., Kruse, J., & Henningsen, P. (2016) · Psychotherapy and Psychosomatics · doi:10.1159/000447701 · Cited by 2,323 · see citing works
Evidence for a central component of post-injury pain hypersensitivity
Woolf, C. J. (1983) · Nature · doi:10.1038/306686a0 · Cited by 2,157 · see citing works
EULAR revised recommendations for the management of fibromyalgia
Macfarlane, G. J., Kronisch, C., Dean, L. E., Atzeni, F., Häuser, W., Fluß, E., Choy, E., Kosek, E., Amris, K., Branco, J., et al. (2017) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-209724 · Cited by 1,566 · cited 2× · see citing works
“did not find them of proven benefit [70], and hence, they are not included in the revised 2016 EULAR recommendations [6].”
BackgroundThe NIMH Research Domain Criteria (RDoC) Project: Precision Medicine for Psychiatry
Insel, T. R. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.14020138 · Cited by 1,472 · cited 1× · see citing works
“One example of such an initiative is the Research Domain Criteria (RDoC) of the NIAMH, which attempts to create an integrative framework for the research, classification, and future treatment of mental disorders, while incorporating evidence ranging from genomics through circuits, with the goal of eventually developin…”
BackgroundEULAR evidence-based recommendations for the management of fibromyalgia syndrome
Carville, S. F., Arendt-Nielsen, S., Bliddal, H., Blotman, F., Branco, J. C., Buskila, D., Da Silva, J. A. P., Danneskiold-Samsøe, B., Dincer, F., Henriksson, C., et al. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.071522 · Cited by 752 · cited 1× · see citing works
“Despite the EULAR recommendations for management of FMS from 2008, recommending the consideration of dopamine agonists [8], a meta-analysis conducted by Sommer et al.”
MethodYarnitsky, D. (2010) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0b013e32833c348b · Cited by 745 · cited 1× · see citing works
“+us, medications that modulate levels of these neurotransmitters in the CNS have the potential to improve CPM and reduce central sensitization [40, 41].”
BackgroundPractical considerations in medical cannabis administration and dosing
MacCallum, C. A., & Russo, E. B. (2018) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2018.01.004 · Cited by 663 · cited 1× · see citing works
“+e THC:CBD therefore determines the product’s overall effect [71].”
BackgroundCrofford, L. J., Rowbotham, M. C., Mease, P. J., Russell, I. J., Dworkin, R. H., Corbin, A. E., Young, J. P., LaMoreaux, L., Martin, S. A., Sharma, U., et al. (2005) · Arthritis & Rheumatism · doi:10.1002/art.20983 · Cited by 651 · cited 1× · see citing works
“However, compared to placebo, it was not found to significantly improve complaints of fatigue in some trials, and none of the trials indicated any improvement in depressive symptoms [20, 21, 53].”
ResultYunus, M. B. (2008) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2007.09.003 · Cited by 648 · see citing works
Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity
Napadow, V., LaCount, L., Park, K., As‐Sanie, S., Clauw, D. J., & Harris, R. E. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27497 · Cited by 645 · cited 2× · see citing works
“Indeed, increased connectivity between different brain areas is a known phenomenon in FMS [46].”
BackgroundWidespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition
Julien, N., Goffaux, P., Arsenault, P., & Marchand, S. (2005) · Pain · doi:10.1016/j.pain.2004.12.032 · Cited by 634 · cited 1× · see citing works
“In humans, such two descending pain inhibitory pathways exist: the noradrenaline/serotonin-mediated pathway and the opioidmediated one [62].”
BackgroundDecreased Central μ-Opioid Receptor Availability in Fibromyalgia
Harris, R. E., Clauw, D. J., Scott, D., McLean, S. A., Gracely, R. H., & Zubieta, J. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2849-07.2007 · Cited by 512 · cited 1× · see citing works
“Reduced availability was inversely correlated with clinical pain ratings [64].”
BackgroundMechanism of action of memantine
Johnson, J. M., & Kotermanski, S. E. (2005) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2005.09.007 · Cited by 500 · cited 1× · see citing works
“Memantine, another receptor antagonist, was suggested to be useful because of its ability to reduce neurotoxicity caused by high levels of glutamate found in different brain areas of FMS patients [31, 32].”
BackgroundJones, G. T., Atzeni, F., Beasley, M., Flüß, E., Sarzi‐Puttini, P., & Macfarlane, G. J. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38905 · Cited by 468 · cited 1× · see citing works
“Fibromyalgia syndrome (FMS) is a common pain disorder, characterized by chronic generalized pain, with a population-estimated prevalence of 1–5% [1].”
BackgroundFitzcharles, M.-A., Ste-Marie, P. A., Goldenberg, D. L., Pereira, J. X., Abbey, S., Choinière, M., Ko, G., Moulin, D. E., Panopalis, P., Proulx, J., et al. (2013) · Pain Research and Management · doi:10.1155/2013/918216 · Cited by 409 · see citing works
Fibromyalgia patients show an abnormal dopamine response to pain
Wood, P. B., Schweinhardt, P., Jaeger, E., Dagher, A., Hakyemez, H., Rabiner, E. A., Bushnell, M. C., & Chizh, B. A. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05623.x · Cited by 406 · cited 1× · see citing works
“Evidence indicating involvement of dopaminergic pathways in the pathophysiology of FMS has led to attempts to develop medications intervening in dopaminergic metabolism [68].”
BackgroundNabilone for the treatment of pain in fibromyalgia.
Skrabek, R. Q., Galimova, L., Ethans, K., & Perry, D. (2008) · The Journal of Pain · doi:10.1016/j.jpain.2007.09.002 · Cited by 384 · cited 1× · see citing works
“reported a reduction in pain, as well as level of anxiety, and an improved quality of life when using nabilone in comparison with placebo [26].”
BackgroundDougherty, P. M., Paleček, J., Palečková, V., Sorkin, L. S., & Willis, W. H. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-08-03025.1992 · Cited by 367 · cited 1× · see citing works
“Activated by a variety of agonists, including substance P and neurokinin, it is known to be involved in the pathogenesis of central sensitization [80], a trait for which efforts were made to develop NMDA antagonists as therapeutic options for FMS, as well as other disorders resulting from central sensitization.”
BackgroundLiu, B., Du, L., & Hong, J.-S. (2000) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39275-4 · Cited by 347 · cited 1× · see citing works
“Inhibition of microglial activation by naltrexone or naloxone therefore has an anti-inflammatory effect through the decrease in production of neurotoxic chemicals [66, 67], which is suggested to contribute to its analgesic effect [25].”
BackgroundElevated insular glutamate in fibromyalgia is associated with experimental pain
Harris, R. E., Sundgren, P. C., Craig, A. D., Kirshenbaum, E., Sen, A., Napadow, V., & Clauw, D. J. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24849 · Cited by 328 · cited 1× · see citing works
“Memantine, another receptor antagonist, was suggested to be useful because of its ability to reduce neurotoxicity caused by high levels of glutamate found in different brain areas of FMS patients [31, 32].”
Backgroundvan de Donk, T., Niesters, M., Kowal, M. A., Olofsen, E., Dahan, A., & van Velzen, M. (2018) · Pain · doi:10.1097/j.pain.0000000000001464 · Cited by 317 · cited 1× · see citing works
“+ey found that THC-containing products increased the pain threshold, whereas CBD-containing products increased plasma-THC levels but diminished THC analgesic effect [75].”
BackgroundClauw, D. J., Arnold, L. M., & McCarberg, B. H. (2011) · Mayo Clinic Proceedings · doi:10.4065/mcp.2011.0206 · Cited by 314 · see citing works
The Effects of Nabilone on Sleep in Fibromyalgia: Results of a Randomized Controlled Trial
Ware, M. A., Fitzcharles, M.-A., Joseph, L., & Shir, Y. (2010) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3181c76f70 · Cited by 313 · see citing works
Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation
Albrecht, D. S., Forsberg, A., Sandström, A., Bergan, C., Kadetoff, D., Protsenko, E., Lampa, J., Lee, Y. C., Höglund, C. O., Catana, C., et al. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.09.018 · Cited by 310 · see citing works
Narrative Review: The Pathophysiology of Fibromyalgia
Abeles, A. M., Pillinger, M. H., Solitar, B. M., & Abeles, M. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-10-200705150-00006 · Cited by 284 · cited 1× · see citing works
“Other neurotransmitters, including GABA, cannabinoid receptors, substance P, NGF, and opioid receptors participate in this complex modulation of pain transmission [42], therefore functioning as optional therapeutic targets.”
BackgroundArnold, L. M., Russell, I. J., Diri, E. W., Duan, W. R., Young, J. P., Sharma, U., Martin, S. A., Barrett, J. A., & Haig, G. (2008) · The Journal of Pain · doi:10.1016/j.jpain.2008.03.013 · Cited by 277 · see citing works
Napadow, V., Kim, J., Clauw, D. J., & Harris, R. E. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34412 · Cited by 276 · see citing works
Treatment of fibromyalgia with cyclobenzaprine: A meta‐analysis
Tofferi, J. K., Jackson, J. L., & O’Malley, P. G. (2004) · Arthritis Care & Research · doi:10.1002/art.20076 · Cited by 268 · cited 1× · see citing works
“A systematic review of the literature reported that it has a moderate benefit in improving sleep disturbances and only a mild improvement in pain [17].”
BackgroundSystematic review with meta-analysis: cytokines in fibromyalgia syndrome
Üçeyler, N., Häuser, W., & Sommer, C. (2011) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-12-245 · Cited by 260 · see citing works
Sosa-Reina, M. D., Nunez-Nagy, S., Gallego-Izquierdo, T., Pecos-Martín, D., Monserrat, J., & Álvarez-Mon, M. (2017) · BioMed Research International · doi:10.1155/2017/2356346 · Cited by 246 · see citing works
Häuser, W., Bernardy, K., Üçeyler, N., & Sommer, C. (2009) · Pain · doi:10.1016/j.pain.2009.05.014 · Cited by 243 · cited 1× · see citing works
“A meta-analysis of randomized controlled trials regarding both pregabalin and gabapentin further emphasized their effect in improving pain, fatigue, sleep, and overall quality of life, in addition to their lack of effect on depressive symptoms and relatively nonsubstantial effect on anxiety [22].”
BackgroundSerotonin-Norepinephrine Reuptake Inhibitors for Pain Control: Premise and Promise
Marks, D., Shah, M., Patkar, A. A., Masand, P. S., Park, G., & Pae, C. (2009) · Current Neuropharmacology · doi:10.2174/157015909790031201 · Cited by 237 · cited 1× · see citing works
“Despite the theoretical assumption, that the combined inhibition of serotonin and noradrenaline is more efficacious than selective serotonin augmentation vis-à-vis the inhibition of pain [51], the use of this class of drugs is recommended in practice guidelines [8–10, 15].”
BackgroundBernardy, K., Klose, P., Welsch, P., & Häuser, W. (2018) · European Journal of Pain · doi:10.1002/ejp.1121 · Cited by 217 · cited 1× · see citing works
“NYX-2925 ((2S,3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo2,5-diazaspiro[3,4]octan-2-yl)butanamide) is a new NMDA receptor modulator which was shown by Khan et al.”
BackgroundFibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study
Younger, J., & Mackey, S. (2009) · Pain Medicine · doi:10.1111/j.1526-4637.2009.00613.x · Cited by 216 · cited 1× · see citing works
“+e beneficial effect of naltrexone on fibromyalgia symptoms was shown by Youner and Mackey in a pilot study in 2009 [24], with a randomized controlled trial published in 2013, finding it to be superior to placebo in reducing pain and associated depressive symptoms [25].”
BackgroundYounger, J., Noor, N., McCue, R., & Mackey, S. (2013) · Arthritis & Rheumatism · doi:10.1002/art.37734 · Cited by 209 · cited 2× · see citing works
“Inhibition of microglial activation by naltrexone or naloxone therefore has an anti-inflammatory effect through the decrease in production of neurotoxic chemicals [66, 67], which is suggested to contribute to its analgesic effect [25].”
BackgroundThe endogenous cannabinoid system and its role in nociceptive behavior
Cravatt, B. F., & Lichtman, A. H. (2004) · Journal of Neurobiology · doi:10.1002/neu.20080 · Cited by 203 · cited 1× · see citing works
“+eir agonists act along sensory pathways as modulators of pain [72].”
BackgroundThe Role of Antidepressants in the Management of Fibromyalgia Syndrome
Häuser, W., Wolfe, F., Tölle, T. R., Üçeyler, N., & Sommer, C. (2012) · CNS Drugs · doi:10.2165/11598970-000000000-00000 · Cited by 199 · cited 1× · see citing works
“+e effect size for improvement in sleep disorders was found to be nonsubstantial [16].”
BackgroundHarris, R. E., Sundgren, P. C., Pang, Y., Hsu, M. C., Petrou, M., Kim, S., McLean, S. A., Gracely, R. H., & Clauw, D. J. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23223 · Cited by 199 · cited 1× · see citing works
“+ese high glutamate levels were found to be related to the severity of FMS symptoms [81].”
BackgroundEmployees With Fibromyalgia: Medical Comorbidity, Healthcare Costs, and Work Loss
White, L. A., Birnbaum, H. G., Kaltenboeck, A., Tang, J., Mallett, D., & Robinson, R. L. (2008) · Journal of Occupational & Environmental Medicine · doi:10.1097/jom.0b013e31815cff4b · Cited by 168 · cited 1× · see citing works
“Comorbid conditions, including mood disorders, anxiety, headaches, irritable bowel syndrome, sleep disturbances, and chronic fatigue syndrome, are found in a large percentage of FMS patients [2, 44, 45].”
BackgroundCerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain
Baraniuk, J. N., Whalen, G., Cunningham, J., & Clauw, D. J. (2004) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-5-48 · Cited by 167 · cited 1× · see citing works
“suggested an excess of endogenous opioids in FMS [63].”
BackgroundSerotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia syndrome
Häuser, W., Urrútia, G., Tort, S., Üçeyler, N., & Walitt, B. T. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010292 · Cited by 164 · cited 2× · see citing works
“A meta-analysis reviewing five different studies regarding duloxetine and five different studies regarding and milnacipran showed that these drugs had positive effects on pain and patient-perceived clinical improvement [12].”
Ablin, J. N., Fitzcharles, M., Buskila, D., Shir, Y., Sommer, C., & Häuser, W. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/485272 · Cited by 161 · see citing works
Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions
Aaron, L. A., & Buchwald, D. (2003) · Best Practice & Research Clinical Rheumatology · doi:10.1016/s1521-6942(03)00033-0 · Cited by 152 · cited 1× · see citing works
“Comorbid conditions, including mood disorders, anxiety, headaches, irritable bowel syndrome, sleep disturbances, and chronic fatigue syndrome, are found in a large percentage of FMS patients [2, 44, 45].”
BackgroundWalitt, B. T., Klose, P., Fitzcharles, M., Phillips, T., & Häuser, W. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011694.pub2 · Cited by 143 · cited 1× · see citing works
“concluded that no convincing evidence suggests that nabilone is useful in treating people with FMS [28].”
BackgroundEfficacy and Safety of Lacosamide in Diabetic Neuropathic Pain
Wymer, J. P., Simpson, J. N., Sen, D. L., & Bongardt, S. (2009) · Clinical Journal of Pain · doi:10.1097/ajp.0b013e318196d2b6 · Cited by 136 · cited 1× · see citing works
“It was also found effective in a placebo-controlled, doubleblind trial for treating neuropathic pain [55].”
BackgroundEmerging Trends in Pain Modulation by Metabotropic Glutamate Receptors
Pereira, V., & Goudet, C. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00464 · Cited by 134 · cited 1× · see citing works
“Central sensitization of pain transmission pathways is associated with hyperexcitability of the glutamatergic system, which leads symptoms observed in persons suffering from chronic pain [79].”
BackgroundSafety and Efficacy of Medical Cannabis in Fibromyalgia
Sagy, I., Schleider, L. B., Abu‐Shakra, M., & Novack, V. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8060807 · Cited by 133 · cited 1× · see citing works
“+e researchers showed a significant reduction in average pain intensity, sleep disturbance, and depression-related symptoms [76].”
BackgroundFiz, J., Durán, M., Capellà, D., Abelló, J. C., & Farré, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018440 · Cited by 132 · cited 1× · see citing works
“reported a significant relief in pain two hours after consumption [74].”
BackgroundResting state connectivity correlates with drug and placebo response in fibromyalgia patients
Schmidt-Wilcke, T., Ichesco, E., Hampson, J. P., Kairys, A., Peltier, S., Harte, S., Clauw, D. J., & Harris, R. E. (2014) · NeuroImage: Clinical · doi:10.1016/j.nicl.2014.09.007 · Cited by 122 · cited 2× · see citing works
“Once such an integrative matrix is put in place, future clinicians will hopefully be able to treat specific patients based on their individual genetic (and pharmcogenetic) characteristics, together with an individualized analysis of connectivity patterns (notably, initial research in this direction is already underway…”
ResultAn update on pharmacotherapy for the treatment of fibromyalgia
Calandre, E. P., Rico‐Villademoros, F., & Slim, M. (2015) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2015.1047343 · Cited by 119 · cited 5× · see citing works
“Several randomized controlled trials, meta-analysis [11, 12]”
BackgroundInfluentialManagement of fibromyalgia: practical guides from recent evidence-based guidelines
Häuser, W., Ablin, J. N., Perrot, S., & Fitzcharles, M. (2017) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.3877 · Cited by 109 · see citing works
Gür, A., Karakoç, M., Nas, K., Çevik, R., Saraç, A. J., & Ataoğlu, S. (2002) · Rheumatology International · doi:10.1007/s00296-002-0221-z · Cited by 107 · see citing works
Lacosamide for neuropathic pain and fibromyalgia in adults
Hearn, L., Derry, S., & Moore, R. A. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009318.pub2 · Cited by 95 · see citing works
Krell, H. V., Leuchter, A. F., Cook, I. A., & Abrams, M. (2005) · Psychosomatics · doi:10.1176/appi.psy.46.5.379 · Cited by 94 · cited 1× · see citing works
“Selective noradrenaline reuptake inhibitors (NRIs), such as reboxetine and its enantiomer esreboxetine, were also suggested as possible treatments for FMS, while the body of evidence regarding the efficacy of reboxetine is rather sporadic and is based mostly on case reports [13], esreboxetine was shown to reduce pain,…”
BackgroundMoldofsky, H., HARRIS, H. W., Archambault, W. T., KWONG, T., & Lederman, S. M. (2011) · The Journal of Rheumatology · doi:10.3899/jrheum.110194 · Cited by 93 · cited 1× · see citing works
“have previously shown that bedtime very low doses of cyclobenzaprine were shown to significantly improve pain and sleep in patients with a specific sleep architecture [18].”
BackgroundEthanol-enhanced GABA release: A focus on G protein-coupled receptors
Kelm, M. K., Criswell, H. E., & Breese, G. R. (2010) · Brain Research Reviews · doi:10.1016/j.brainresrev.2010.09.003 · Cited by 88 · cited 12× · see citing works
“+e two main members of this family of drugs, pregabalin and gabapentin, act by binding to the alpha2delta subunit of voltage-gated calcium channels in the CNS. Originally used as anticonvulsants, they are currently mainly used for the treatment of chronic pain [11].”
BackgroundInfluentialOliván‐Blázquez, B., Herrera‐Mercadal, P., Puebla‐Guedea, M., Pérez‐Yus, M., Andres, E. M., Fayed, N. M., del Hoyo, Y. L., Magallón-Botaya, R. M., Roca, M., & García‐Campayo, J. (2014) · Pain · doi:10.1016/j.pain.2014.09.004 · Cited by 87 · cited 1× · see citing works
“A double-blind, randomized-controlled trial published in 2014 found memantine to achieve a significant reduction in pain [33], with another hypothesis suggesting the combined use of pregabalin and memantine to concomitantly affect voltage-gated calcium channels and NMDA receptors, as a possible therapeutic approach [8…”
BackgroundOhta, H., Oka, H., Usui, C., Ohkura, M., Suzuki, M., & Nishioka, K. (2012) · Arthritis Research & Therapy · doi:10.1186/ar4056 · Cited by 80 · cited 1× · see citing works
“However, compared to placebo, it was not found to significantly improve complaints of fatigue in some trials, and none of the trials indicated any improvement in depressive symptoms [20, 21, 53].”
ResultMirogabalin: First Global Approval
Deeks, E. D. (2019) · Drugs · doi:10.1007/s40265-019-01070-8 · Cited by 80 · cited 1× · see citing works
“A newer gabapentinoid, mirogabalin (DS-5565) was shown to have analgesic qualities in animal models of both central and peripheral neuropathies [56], while approved for the treatment of peripheral neuropathy in Japan, its development as a treatment modality for FMS in the USA and Europe was stopped after it failed in…”
BackgroundKim, C. H., Vincent, A., Clauw, D. J., Luedtke, C. A., Thompson, J. M., Schneekloth, T. D., & Oh, T. H. (2013) · Arthritis Research & Therapy · doi:10.1186/ar4200 · Cited by 77 · cited 1× · see citing works
“+e same association was not observed in heavy drinkers [59].”
BackgroundMedikamentöse Therapie des Fibromyalgiesyndroms
Sommer, C., Häuser, W., Alten, R., Petzke, F. W., Späth, M., Tölle, T. R., Üçeyler, N., Winkelmann, A., Winter, E., & Bär, K. (2012) · Der Schmerz · doi:10.1007/s00482-012-1172-2 · Cited by 75 · cited 1× · see citing works
“did not find them of proven benefit [70], and hence, they are not included in the revised 2016 EULAR recommendations [6].”
BackgroundChang, R. C., Rota, C., Glover, R. E., Mason, R. P., & Hong, J. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02267-2 · Cited by 73 · cited 1× · see citing works
“Inhibition of microglial activation by naltrexone or naloxone therefore has an anti-inflammatory effect through the decrease in production of neurotoxic chemicals [66, 67], which is suggested to contribute to its analgesic effect [25].”
BackgroundActions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model
Barnes, N. S. A., Mitchell, V. A., Kazantzis, N. P., & Vaughan, C. W. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13337 · Cited by 70 · cited 1× · see citing works
“Endocannabinoids such as anandamide are metabolized by specific enzymes including fatty acid amide hydrolase (FAAH) and monacylglycerol lipase (MAGL), and agents capable of inhibiting these enzymes are being tested as novel analgesic targets [78].”
BackgroundCohen, S. P., Verdolin, M. H., Chang, A. S., Kurihara, C., Morlando, B. J., & Mao, J. (2006) · Journal of Pain · doi:10.1016/j.jpain.2005.12.010 · Cited by 66 · cited 1× · see citing works
“Ketamine, an NMDA antagonist, was found to reduce muscular and referred pain in FMS patients [30].”
BackgroundManagement of fibromyalgia syndrome – an interdisciplinary evidence-based guideline
Häuser, W., Arnold, B., Eich, W., Felde, E., Flügge, C., Henningsen, P., Herrmann, M., Köllner, V., Kühn, E., Nutzinger, D. O., et al. (2008) · Europe PMC (PubMed Central) · doi:10.3205/000059 · Cited by 60 · see citing works
Weber, J., Schley, M. T., Casutt, M., Gerber, H., Schuepfer, G., Rukwied, R., Schleinzer, W., Ueberall, M. A., & Konrad, C. J. (2009) · Anesthesiology Research and Practice · doi:10.1155/2009/827290 · Cited by 56 · cited 2× · see citing works
“showed dronabinol significantly reduce pain and depressive symptoms in FMS patients with neuropathic pain [29].”
BackgroundFibromyalgia Syndrome: A Discussion of the Syndrome and Pharmacotherapy
Smith, H. S., & Barkin, R. L. (2010) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e3181df8e1b · Cited by 55 · cited 2× · see citing works
“Comorbid conditions, including mood disorders, anxiety, headaches, irritable bowel syndrome, sleep disturbances, and chronic fatigue syndrome, are found in a large percentage of FMS patients [2, 44, 45].”
BackgroundKhan, M. A., Houck, D. R., Gross, A. L., Zhang, X.-L., Cearley, C. N., Madsen, T. M., Kroes, R. A., Stanton, P. K., Burgdorf, J. S., & Moskal, J. R. (2017) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx096 · Cited by 55 · cited 1× · see citing works
“+is finding led to the hypothesis that it would be effective in NMDA receptorassociated CNS disorders [83].”
BackgroundAntihyperalgesic efficacy of lacosamide in a rat model for muscle pain induced by TNF
Beyreuther, B. K., Geis, C., Stöhr, T., & Sommer, C. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.01.012 · Cited by 51 · cited 1× · see citing works
“In animal models, it effectively reduced muscular hyperalgesia and was more effective than gabapentin and pregabalin [54].”
BackgroundShor, D. B., Weitzman, D., Dahan, S., Gendelman, O., On, Y. B., Amital, D., Shalev, V., Chodick, G., & Amital, H. (2017) · The Journal of Rheumatology · doi:10.3899/jrheum.170098 · Cited by 49 · cited 2× · see citing works
“NYX-2925 ((2S,3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo2,5-diazaspiro[3,4]octan-2-yl)butanamide) is a new NMDA receptor modulator which was shown by Khan et al.”
BackgroundCalandre, E. P., Rico‐Villademoros, F., Galan, J. L., Molina-Barea, R., Vilchez, J. S., Rodriguez-lopez, C. M., Hidalgo‐Tallon, J., & Morillas-Arques, P. (2014) · Psychopharmacology · doi:10.1007/s00213-013-3422-0 · Cited by 48 · see citing works
THE EFFECT OF ETHANOL ON THE CONCENTRATION OF γ-AMINOBUTYRIC ACID IN THE RAT BRAIN
Gordon, E. R. (1967) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y67-107 · Cited by 46 · see citing works
Arnold, L. M., Hirsch, I., Sanders, P. W., Ellis, A., & Hughes, B. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34390 · Cited by 40 · cited 1× · see citing works
“Selective noradrenaline reuptake inhibitors (NRIs), such as reboxetine and its enantiomer esreboxetine, were also suggested as possible treatments for FMS, while the body of evidence regarding the efficacy of reboxetine is rather sporadic and is based mostly on case reports [13], esreboxetine was shown to reduce pain,…”
BackgroundMirtazapine for fibromyalgia in adults
Welsch, P., Bernardy, K., Derry, S., Moore, A., & Häuser, W. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012708.pub2 · Cited by 38 · see citing works
Arnold, L. M., Whitaker, S., Hsu, C., Jacobs, D. R., & Merante, D. (2019) · Current Medical Research and Opinion · doi:10.1080/03007995.2019.1629757 · Cited by 33 · see citing works
Smith, S. C., & Wagner, M. (2014) · PubMed · Cited by 32 · see citing works
Distler, O., Eich, W., Dokoupilová, E., Dvorak, Z., Fleck, M., Gaubitz, M., Hechler, M., Jansen, J., Krause, A., Bendszus, M., et al. (2009) · Arthritis & Rheumatism · doi:10.1002/art.25062 · Cited by 29 · cited 1× · see citing works
“With most evidence about the benefit of dopaminergic agonists being sporadic, it is worth mentioning tergulide, which in a randomized, double-blind placebo-controlled trial, was found to improve FMS symptoms in a subgroup of patients with spinal stenosis (as opposed to the comparing all tergulide-assigned patients to…”
BackgroundSaeki, K., Yasuda, S.-I., Kato, M., Kano, M., Domon, Y., Arakawa, N., & Kitano, Y. (2019) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-019-01628-z · Cited by 29 · cited 1× · see citing works
“A newer gabapentinoid, mirogabalin (DS-5565) was shown to have analgesic qualities in animal models of both central and peripheral neuropathies [56], while approved for the treatment of peripheral neuropathy in Japan, its development as a treatment modality for FMS in the USA and Europe was stopped after it failed in…”
BackgroundGhoreishi-Haack, N. S., Priebe, J. M., Aguado, J. D., Colechio, E. M., Burgdorf, J. S., Bowers, M. S., Cearley, C. N., Khan, M. A., & Moskal, J. R. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.249409 · Cited by 27 · cited 2× · see citing works
“Animal models, pending clinical trials in humans [35, 36] Pain Research and Management 3”
BackgroundMethodRecla, J. M., & Sarantopoulos, C. D. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.01.052 · Cited by 26 · cited 1× · see citing works
“A double-blind, randomized-controlled trial published in 2014 found memantine to achieve a significant reduction in pain [33], with another hypothesis suggesting the combined use of pregabalin and memantine to concomitantly affect voltage-gated calcium channels and NMDA receptors, as a possible therapeutic approach [8…”
BackgroundA systematic review and meta‐analysis of memantine for the prevention or treatment of chronic pain
Kurian, R., Raza, K., & Shanthanna, H. (2019) · European Journal of Pain · doi:10.1002/ejp.1393 · Cited by 26 · cited 1× · see citing works
“A recent meta-analysis of 15 studies regarding the benefit of memantine in treating chronic pain (either neuropathic or FMS) concluded that the current evidence regarding memantine for chronic pain is limited and reported an increase in dizziness as a side effect of the medication [34].”
BackgroundHouck, D. R., Sindelar, L., Sanabria, C. R., Stanworth, S. H., Krueger, M., Suh, M., & Madsen, T. M. (2018) · Clinical and Translational Science · doi:10.1111/cts.12584 · Cited by 21 · cited 2× · see citing works
“Animal models, pending clinical trials in humans [35, 36] Pain Research and Management 3”
BackgroundMethodMirtazapine for fibromyalgia in adults
Welsch, P., Bernardy, K., Derry, S., Moore, R. A., & Häuser, W. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012708 · Cited by 20 · see citing works
An update on emerging drugs for fibromyalgia treatment
Atzeni, F., Gerardi, M. C., Masala, I. F., Alciati, A., Batticciotto, A., & Sarzi‐Puttini, P. (2017) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2017.1418323 · Cited by 16 · cited 1× · see citing works
“+us, medications that modulate levels of these neurotransmitters in the CNS have the potential to improve CPM and reduce central sensitization [40, 41].”
BackgroundKonuk, N., Ortancıl, Ö., Bostancı, B., Kıran, S., & Sapmaz, P. (2010) · Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology · doi:10.1080/10177833.2010.11790631 · Cited by 11 · see citing works
Lederman, S. M., Clauw, D. J., Gendreau, J., Arnold, L. M., Moldofsky, H., Mease, P. J., Daugherty, B. L., & Gendreau, R. M. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2015-eular.2014 · Cited by 6 · cited 1× · see citing works
“8mg) has been reported to improve nonrestorative sleep in FMS patients [19]; however, this formulation has 2 Pain Research and Management”
Background
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Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update
Siracusa, R., Paola, R. D., Cuzzocrea, S., & Impellizzeri, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083891 · Cited by 710 · see citing works
Löscher, W., & Klein, P. (2021) · CNS Drugs · doi:10.1007/s40263-021-00827-8 · Cited by 381 · see citing works
Management of Fibromyalgia: An Update
Jones, E. A., Asaad, F. S., Patel, N., Jain, E., & Abd-Elsayed, A. A. (2024) · Biomedicines · doi:10.3390/biomedicines12061266 · Cited by 66 · see citing works
“In a double-blind randomized trial, memantine was found to produce a significant reduction in pain, with a hypothesis that the combination of memantine with pregabalin could achieve therapeutic results in the treatment of fibromyalgia [47].”
BackgroundPain Biomarkers in Fibromyalgia Syndrome: Current Understanding and Future Directions
Favretti, M., Iannuccelli, C., & Franco, M. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310443 · Cited by 68 · see citing works
Khurshid, H., Qureshi, I. A., Jahan, N., Went, T. R., Sultan, W., Sapkota, A., & Alfonso, M. (2021) · Cureus · doi:10.7759/cureus.17332 · Cited by 59 · see citing works
“Regarding the complex function of the endocannabinoid system in pain modulation, it is hypothesized that lack of endocannabinoids activity is among the underlying pathophysiology of FM but there is no clear evidence to support this assumption [1,9,11,15].”
BackgroundInfluentialFibromyalgia and Inflammation: Unrevealing the Connection
García‐Domínguez, M. (2025) · Cells · doi:10.3390/cells14040271 · Cited by 63 · see citing works
Duloxetine for fibromyalgia syndrome: a systematic review and meta-analysis
Migliorini, F., Maffulli, N., Eschweiler, J., Baroncini, A., Bell, A., & Colarossi, G. (2023) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-023-03995-z · Cited by 40 · see citing works
“Three drugs has been currently approved for the pharmacological management of fibromyalgia: duloxetine, milnacipran, and pregabalin [41].”
BackgroundReview of Fibromyalgia (FM) Syndrome Treatments
Cohen-Biton, L., Buskila, D., & Gannot, R. N. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph191912106 · Cited by 36 · see citing works
“Abbreviations FM Fibromyalgia CPM Conditioned pain modulation FSMP Fibromyalgia Self-Management Program CBT Cognitive behavioral therapy MBI Mindfulness-based intervention TEI Trait emotional intelligence SWL Satisfaction with life MBSR Mindfulness-based stress reduction TAU Treatment-as-usual BDNF Brain-derived neuro…”
BackgroundMilnacipran for the Treatment of Fibromyalgia
Gupta, H., Girma, B., Jenkins, J. S., Kaufman, S. E., Lee, C. A., & Kaye, A. D. (2021) · Health Psychology Research · doi:10.52965/001c.25532 · Cited by 35 · see citing works
Bruun, K. D., Christensen, R., Amris, K., Vægter, H. B., Blichfeldt‐Eckhardt, M. R., Bye-Møller, L., Holsgaard‐Larsen, A., & Toft, P. (2023) · The Lancet Rheumatology · doi:10.1016/s2665-9913(23)00278-3 · Cited by 33 · see citing works
Nociplastic pain concept, a mechanistic basis for pragmatic approach to fibromyalgia
Bidari, A., & Ghavidel‐Parsa, B. (2022) · Clinical Rheumatology · doi:10.1007/s10067-022-06229-5 · Cited by 31 · see citing works
Mechanism-based nonopioid analgesic targets
Zeng, X., Powell, R., & Woolf, C. J. (2025) · Journal of Clinical Investigation · doi:10.1172/jci191346 · Cited by 33 · see citing works
“Gabapentinoids (i.e., gabapentin and pregabalin) target the α 2 δ subunit and are widely used for neuropathic pain management with potential applicability for fibromyalgia (27, 91).”
Alfaro-Rodríguez, A., Reyes-Long, S., Roldán-Valadéz, E., González‐Torres, M., Bonilla‐Jaime, H., Bandala, C., Ávila-Luna, A., Bueno-Nava, A., Cabrera-Ruiz, E., Sánchez-Aparicio, P., et al. (2024) · Pharmaceuticals · doi:10.3390/ph17091205 · Cited by 27 · see citing works
“This evidence supports the significant role that these receptors may play in FM [48–50].”
BackgroundCliment‐Sanz, C., Hamilton, K. R., Martínez-Navarro, O., Briones‐Vozmediano, E., Gracia-Lasheras, M., Fernández‐Lago, H., Valenzuela‐Pascual, F., & Finan, P. H. (2023) · Disability and Rehabilitation · doi:10.1080/09638288.2023.2280057 · Cited by 25 · see citing works
“The US Food and Drug Administration approved the use of amitriptyline, duloxetine, and pregabalin for the treatment of fibromyalgia [59].”
Diagnosis and Management of Neuropathic Pain in Spine Diseases
Bielewicz, J., Kamieniak, M., Szymoniuk, M., Litak, J., Czyżewski, W., & Kamieniak, P. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12041380 · Cited by 29 · see citing works
Psychoeducation for Patients with Fibromyalgia: A Systematic Review
Gómez-de-Regil, L. (2021) · Healthcare · doi:10.3390/healthcare9060737 · Cited by 24 · see citing works
“Regardless all efforts, the efficacy of pharmacological treatment is rather modest, often leading to voluntary discontinuation of medication intake as patients with FM perceive little amelioration [11,12].”
BackgroundElkholy, N. S., Shafaa, M. W., & Mohammed, H. S. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166150 · Cited by 22 · see citing works
Pregabalin administration in patients with fibromyalgia: a Bayesian network meta-analysis
Migliorini, F., Maffulli, N., Knobe, M., Tenze, G., Aljalloud, A., & Colarossi, G. (2022) · Scientific Reports · doi:10.1038/s41598-022-16146-x · Cited by 22 · see citing works
“Fibromyalgia – are there any new approaches?”
Martinez, J. E., & Guimarães, I. (2024) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2024.101933 · Cited by 22 · see citing works
Wang, C., Erridge, S., Holvey, C., Coomber, R., Usmani, A., Sajad, M., Guru, R., Holden, W., Rucker, J., Platt, M. W., et al. (2023) · Brain and Behavior · doi:10.1002/brb3.3072 · Cited by 22 · see citing works
“It has been hypothesized that a deficiency of endocannabinoid activity may play a role in the pathophysiology of fibromyalgia (Cameron & Hemingway, 2020; Tzadok & Ablin, 2020).”
BackgroundLow-dose naltrexone’s utility for non-cancer centralized pain conditions: a scoping review
Rupp, A., Young, E. E., & Chadwick, A. L. (2023) · Pain Medicine · doi:10.1093/pm/pnad074 · Cited by 24 · see citing works
Effect of Resistance Exercises on Function and Pain in Fibromyalgia
Wang, J.-J., Tam, K., Hsiao, H., Liou, T., Rau, C.-L., & Hsu, T.-H. (2023) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000002318 · Cited by 19 · see citing works
Mind-body therapy for treating fibromyalgia: a systematic review
Steen, J. P., Kannan, V., Zaidi, A., Cramer, H., & Ng, J. Y. (2024) · Pain Medicine · doi:10.1093/pm/pnae076 · Cited by 27 · see citing works
Gómez-Pérez, M. C., García-Palacios, A., Castilla, D., Zaragozá, I., & Suso-Ribera, C. (2020) · Pain Research and Management · doi:10.1155/2020/7897268 · Cited by 18 · see citing works
“, Cognitive Behavioral ,erapy, CBT) options for FM [6, 7].”
BackgroundExploring the anti-hyperalgesic effects of ethyl gallate in fibromyalgia-like behaviors in mice
Gonçalves, E. C. D., Gonçalves, T. R., Raposo, N. R. B., Simonelli, M., Capasso, R., & Dutra, R. C. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118685 · Cited by 16 · see citing works
Fibromyalgia pathogenesis explained by a neuroendocrine multistable model
Demori, I., Losacco, S., Giordano, G., Mucci, V., Blanchini, F., & Burlando, B. (2024) · PLOS ONE · doi:10.1371/journal.pone.0303573 · Cited by 14 · see citing works
Demori, I., Giordano, G., Mucci, V., Losacco, S., Marinelli, L., Massobrio, P., Blanchini, F., & Burlando, B. (2022) · Journal of Computational Neuroscience · doi:10.1007/s10827-022-00826-8 · Cited by 14 · see citing works
“It is noteworthy that gabapentinoids and NMDA antagonists both act by depressing the glutamatergic function in favor of the GABAergic one, and in addition that pregabalin is one of the three drugs that have been approved in the treatment of FM by the US FDA (Tzadok & Ablin, 2020).”
BackgroundInfluentialHenley, P. P., Martins, T., & Zamani, R. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20247185 · Cited by 14 · see citing works
“Subsequently, over the past 20 years, there have been many clinical trials investigating the repurposing of existing pharmaceutical treatments for managing fibromyalgia pain and accompanying symptoms [21–23].”
BackgroundPlacebo effect in pharmacological management of fibromyalgia: a meta-analysis
Migliorini, F., Maffulli, N., Eschweiler, J., Betsch, M., Tingart, M., & Colarossi, G. (2021) · British Medical Bulletin · doi:10.1093/bmb/ldab015 · Cited by 14 · see citing works
Rivas, L. M., & Alcocer, I. L. A. (2022) · Rehabilitation and Sports Medicine · doi:10.56294/ri202223 · Cited by 13 · see citing works
Dorta, D. C., Colavolpe, P. O., Lauria, P. S. S., Fonseca, R. B., Brito, V. C. S. G., & Villarreal, C. F. (2024) · EXPLORE · doi:10.1016/j.explore.2024.103016 · Cited by 16 · see citing works
A Comprehensive Analysis of Fibromyalgia and the Role of the Endogenous Opioid System
García‐Domínguez, M. (2025) · Biomedicines · doi:10.3390/biomedicines13010165 · Cited by 13 · see citing works
Efficacy of cannabinoids in fibromyalgia: a literature review
Anaya, H. J. M., Ortiz, M. P. T., Valencia, D. H. F., & Ribero, O. F. G. (2021) · Colombian Journal of Anesthesiology · doi:10.5554/22562087.e980 · Cited by 13 · see citing works
“(3) Fibromyalgia affects between 2-5 % of the population (4,5) and is more frequent in women with a mean age between 30 and 50 years.”
BackgroundDu, M., Hou, X., Lu, S., Kang, T., Li, Y., & Wang, R. (2023) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.14924 · Cited by 12 · see citing works
Munipalli, B., Chauhan, M., Morris, A. M., Ahmad, R., Fatima, M., Allman, M. E., Niazi, S. K., & Bruce, B. K. (2024) · Journal of Primary Care & Community Health · doi:10.1177/21501319241281221 · Cited by 15 · see citing works
“11 The understanding of FM has undergone a significant evolution.”
BackgroundIlari, S., Passacatini, L. C., Malafoglia, V., Oppedisano, F., Maiuolo, J., Gliozzi, M., Palma, E., Tomino, C., Fini, M., Raffaeli, W., et al. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106547 · Cited by 12 · see citing works
The Association of Current Tobacco Status With Pain and Symptom Severity in Fibromyalgia Patients
Croghan, I. T., Hurt, R. T., Ganesh, R., Bhagra, O., Fischer, K. M., Vincent, A., Hays, J. T., Bierle, D. M., Schroeder, D. R., Fuehrer, D. L., et al. (2021) · Mayo Clinic Proceedings Innovations Quality & Outcomes · doi:10.1016/j.mayocpiqo.2021.03.008 · Cited by 10 · see citing works
“Fibromyalgiaspecific pharmacotherapy indicates use of US Food and Drug Administrationeapproved medications for fibromyalgia, including duloxetine, milancipram, pregabalin, and other medications such as gabapentin, tricyclics, and low-dose naltrexone that are supported by evidence.(20) Opioid medications that were used…”
BackgroundTranchida, N., Inferrera, F., Impellizzeri, D., D’Amico, R., Siracusa, R., Fusco, R., Cuzzocrea, S., Cordaro, M., & Paola, R. D. (2024) · Journal of Functional Foods · doi:10.1016/j.jff.2024.106387 · Cited by 9 · see citing works
Shing, C. H., Wang, F., Lau, L. N. L., Lam, P. M., Ho, H. C., & Wong, S. S. C. (2024) · Regional Anesthesia & Pain Medicine · doi:10.1136/rapm-2024-105776 · Cited by 8 · see citing works
“While certain studies (such as studies 9, 10, and 14) exhibited higher influence metrics, their exclusion did not substantially alter the overall results of the meta-analyses (online supplemental file 9 and 10).”
Kamal, M.-A. M., Essam, R. M., Abdelkader, N. F., & Zaki, H. F. (2025) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-025-10194-6 · Cited by 10 · see citing works
“Only pre-gabalin, duloxetine, and milnacipran have received FDA approval to manage FMS (Tzadok and Ablin 2020).”
Managing Pain in Fibromyalgia: Current and Future Options
Clarke, H. A., Peer, M., Miles, S. J., & Fitzcharles, M. (2025) · Drugs · doi:10.1007/s40265-025-02204-x · Cited by 9 · see citing works
“This suboptimal effect of current drugs for FM is reflected by fewer than half of rheumatologists believing that effective treatments for FM exist [12, 108].”
Depression in Fibromyalgia Patients May Require Low-Dose Naltrexone to Respond: A Case Report
Siembida, J., & Johnson, B. (2022) · Cureus · doi:10.7759/cureus.22677 · Cited by 8 · see citing works
“An additional mechanism of naltrexone’s therapeutic actions may involve decreasing the inflammatory response in fibromyalgia by antagonizing microglial toll-like receptors [11].”
BackgroundRosenberg, V., Tzadok, R., Chodick, G., & Kariv, R. (2021) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.5352 · Cited by 8 · see citing works
Self-citationFibromyalgia Animal Models Using Intermittent Cold and Psychological Stress
Ueda, H., & Neyama, H. (2023) · Biomedicines · doi:10.3390/biomedicines12010056 · Cited by 9 · see citing works
“In the US, there are only three FDA-approved pharmacological treatments for FM [17].”
BackgroundWhole-Body Cryostimulation: An Effective Complementary Treatment in Fibromyalgia? A Follow Up Study
Verme, F., Majdič, N., Modaffari, G., Alito, A., Scarpa, A., Piterà, P., Brunani, A., Fontana, J. M., & Capodaglio, P. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14080836 · Cited by 7 · see citing works
“The typical components of these multidisciplinary programmes for FM usually include educational, cognitive and behavioural interventions, physical training [22], and medication [23].”
BackgroundVarallo, G., Cattivelli, R., Giusti, E. M., Landi, G., Spatola, C. A. M., Ruggiero, G. M., Franceschini, C., Tossani, E., Grandi, S., Capodaglio, P., et al. (2023) · Clinical and Experimental Rheumatology · doi:10.55563/clinexprheumatol/7hvaya · Cited by 7 · see citing works
Neural indices of multimodal sensory and autonomic hyperexcitability in fibromyalgia
Marinković, K., Woodruff, D., White, D. R., Caudle, M. M., & Cronan, T. A. (2023) · Neurobiology of Pain · doi:10.1016/j.ynpai.2023.100140 · Cited by 7 · see citing works
“Gabapentinoid medications are commonly prescribed for the treatment of FM (Cooper et al., 2017; Tzadok and Ablin, 2020).”
BackgroundPharmacological Treatment of Fibromyalgia
Guymer, E. K., & Littlejohn, G. O. (2021) · Springer eBooks · doi:10.1007/978-3-030-78638-0_4 · Cited by 7 · see citing works
Perimenopause in women with rheumatologic diseases: a spotlight on an under-addressed transition
Shimol, J. B. (2023) · Climacteric · doi:10.1080/13697137.2023.2276201 · Cited by 6 · see citing works
“Nonetheless, compliance with these drugs has remained low as a result of limited efficacy and multiple side effects [67].”
BackgroundSeekins, C. A., Welborn, A. M., Schwarz, A. M., & Streicher, J. M. (2024) · Pharmacological Reports · doi:10.1007/s43440-024-00687-1 · Cited by 6 · see citing works
“Serotonin-Norepineph-rine Reuptake Inhibitors (SNRI) such as duloxetine and milnacipran are often prescribed to manage fibromyalgia symptoms, as many patients have dysregulated monoamine neurotransmitters [ 12 , 13].”
Minakawa, Y., Saito, S., Matsumoto, Y., Oka, H., Miki, K., Yukioka, M., & Itoh, K. (2022) · Medical Acupuncture · doi:10.1089/acu.2022.0005 · Cited by 6 · see citing works
Mao, S., Qian, G., Xiao, K., Xu, H., Zhang, S., & Zhou, W.-S. (2024) · Perceptual and Motor Skills · doi:10.1177/00315125241291080 · Cited by 6 · see citing works
“Regarding FMS treatment, no single therapy or medication regimen has consistently yielded highly effective results (Tzadok & Ablin, 2020).”
Inferrera, F., Tranchida, N., Fusco, R., Cuzzocrea, S., Impellizzeri, D., Siracusa, R., D’Amico, R., Rashan, L. J., Badaeva, A. V., Danilov, A. B., et al. (2025) · Neurochemistry International · doi:10.1016/j.neuint.2025.106057 · Cited by 5 · see citing works
Rasmussen, M. U., Christensen, R., Wæhrens, E. E., Henriksen, M., Duhn, P. H., Bliddal, H., & Amris, K. (2025) · Annals of the Rheumatic Diseases · doi:10.1016/j.ard.2025.07.008 · Cited by 5 · see citing works
Maggi, B. G., Lima, N. L., de Lara, L. H. C., Moura, M. J. H., Grüdtner, D. O. M., & Hillal, J. P. D. (2025) · Pain Management · doi:10.1080/17581869.2025.2569299 · Cited by 4 · see citing works
Vatvani, A. D., Patel, P., Hariyanto, T. I., & Yanto, T. A. (2024) · The Korean journal of pain · doi:10.3344/kjp.24202 · Cited by 4 · see citing works
Castaldo, G., Marino, C., D’Elia, M., Grimaldi, M., Napolitano, E., D’Ursi, A. M., & Rastrelli, L. (2024) · Nutrients · doi:10.3390/nu16234161 · Cited by 4 · see citing works
Latifoglou, E., Çınar, E., Tanıgör, G., & On, A. Y. (2022) · Disability and Rehabilitation · doi:10.1080/09638288.2022.2127931 · Cited by 5 · see citing works
Duloxetine induced tachycardia: A rare side effect
Yalçınkaya, B., Tüten, B., Yazar, B., Demirel, K., & Ocak, H. (2022) · Pain Practice · doi:10.1111/papr.13174 · Cited by 4 · see citing works
Body reprogramming for fibromyalgia and central sensitivity syndrome: A preliminary evaluation
Lanario, J. W., Hudson, E. F., Locher, C., Dee, A., Elliot, K., & Davies, A. F. (2023) · SAGE Open Medicine · doi:10.1177/20503121231207207 · Cited by 4 · see citing works
Guerin, C., Attli, B., Cooley, K., Hassan, S. I., Sarebanha, S., Sadrolsadot, P., & Chung, C. (2022) · Journal of Integrative and Complementary Medicine · doi:10.1089/jicm.2021.0231 · Cited by 4 · see citing works
Assessment of physicians’ knowledge and awareness of fibromyalgia: a cross-sectional study
Emorinken, A., Dic‐Ijiewere, M. O., Agbadaola, O. R., Oseni, T. I. A., Echekwube, P. O., Ugheoke, A. J., & Aikhuomogbe, O. M. (2022) · International Journal of Advances in Medicine · doi:10.18203/2349-3933.ijam20220435 · Cited by 3 · see citing works
Prevalence and Clinical Significance of Metabolic Syndrome in Fibromyalgia Patients
Yahia, M., Makboul, K. S., & Ali, H. F. (2021) · Aktuelle Rheumatologie · doi:10.1055/a-1463-2253 · Cited by 3 · see citing works
“However, reduced conditioned pain modulation and neural over-sensitization are suggested mechanisms [2].”
BackgroundYeh, Y.-A., Hsu, H., Lin, M., Chen, T., Lin, W.-C., Huang, H., & Lin, Y. (2024) · Life · doi:10.3390/life14111499 · Cited by 3 · see citing works
Kinin B1 receptor is involved in mechanical nociception in a fibromyalgia-like model in mice
Dagnino, A. P. A., Azevedo, V. M., Oliboni, P., Campos, M. M., & Maciel, I. D. S. (2020) · Journal for Reproducibility in Neuroscience · doi:10.31885/jrn.1.2020.1431 · Cited by 3 · see citing works
“Additionally, fibromyalgia treatment is complex, and the current pharmacological options available display limited effects and often have adverse side effects (7,8) .”
BackgroundPain Management in Fibromyalgia: Evaluating the Roles of Pregabalin, Duloxetine, and Milnacipran
Ejaz, K. F., Wani, R., Akbar, A., Khan, Q. U., Ishtiaq, H., Amir, M., Ali, A. I., & Khan, S. U. (2024) · Cureus · doi:10.7759/cureus.76631 · Cited by 3 · see citing works
Fibromyalgia from a psychiatric point of view
Hasterok, M., Piegza, M. J., & Dębski, P. G. (2021) · Psychiatria i Psychologia Kliniczna · doi:10.15557/pipk.2021.0014 · Cited by 3 · see citing works
Barrot, M., Basile, H.-P., & Kremer, M. (2025) · Advances in neurobiology · doi:10.1007/978-3-031-96364-3_12 · Cited by 2 · see citing works
The 4th International Virtual Congress on Controversies in Fibromyalgia
Ablin, J. N., & Sarzi‐Puttini, P. (2022) · Clinical and Experimental Rheumatology · doi:10.55563/clinexprheumatol/ajiygc · Cited by 2 · see citing works
“The complexity of the fatigue experience in patients with RA, encompassing physical, cognitive, daily living and emotional impacts, can be difficult to be managed (11, 12).”
BackgroundPrevalência da dor e percepção do tratamento em pacientes com fibromialgia
de Araújo, L. V. F., Caires, P. T. P. R. C., Pinheiro, T. G., Gusmão, L. C., Santos, L. A., Souza, D. C., de Lima, C. R. C., Correia, F. S. A., de Oliveira, D. A., & Lessa, R. S. (2022) · Revista Eletrônica Acervo Saúde · doi:10.25248/reas.e10856.2022 · Cited by 2 · see citing works
Uma abordagem geral da Fibromialgia: revisão de literatura
de Athayde, I. B., Marques, E. T. D. F., & Côrtes, J. P. D. R. (2022) · Revista Eletrônica Acervo Médico · doi:10.25248/reamed.e10934.2022 · Cited by 2 · see citing works
Identification of the Involvement of Potassium Channels in Fibromyalgia
Lawson, K. (2022) · Frontiers in Bioscience-Scholar · doi:10.31083/j.fbs1404029 · Cited by 2 · see citing works
“The benefits reported have been dose-related pain alleviation with improvement in quality of life and sleep [40].”
BackgroundPfalzgraf, A. R., Friend, R. M., & Jones, K. D. (2023) · Pain Management Nursing · doi:10.1016/j.pmn.2023.10.005 · Cited by 2 · see citing works
Zhang, C. Y., Zhang, P., Zhao, Y., Liu, Y., Yun, H., Zhu, Z., & Xiao, H. (2025) · Journal of Medical Internet Research · doi:10.2196/71624 · Cited by 2 · see citing works
“…with fibromyalgia who have been taking medication for a long time have adverse reactions such as dizziness, drowsiness, nausea, and vomiting, and some even stop taking the drug on their own because they cannot tolerate the adverse reactions [6,7], which results in the continued use of medication.”
Häuser, W. (2020) · Aktuelle Rheumatologie · doi:10.1055/a-1182-5630 · Cited by 2 · see citing works
“Die Liste der Medikamente, welche in RCTs keine Überlegenheit gegenüber Placebo zeigten bzw. in keinen weiteren Studien getestet wurden, ist lang [ 48 ].”
Duloxetine: an effective treatment for fibromyalgia syndrome?
Elahi, N., & Ellahi, A. (2023) · International Journal of Surgery Global Health · doi:10.1097/gh9.0000000000000093 · Cited by 2 · see citing works
Tobajas, Y., Alemany-Fornés, M., Samarra, I., Romero‐Giménez, J., Castellana, J. C., Tintoré, M., del Pino, A., Canela-Canela, N., Bas-Prior, J. M. D., Ortega-Olivé, N., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13030792 · Cited by 2 · see citing works
“Fibromyalgia management often involves medications related to mental health or neurological conditions (antidepressants or anticonvulsants are also prescribed to reduce pain and enhance mood) [31–33] and their classifications reflect their mechanisms of action and therapeutic purposes.”
BackgroundAkbarian, M., PhD Candidate, D. O. H. P., Saeidi, N., MSc, D. O. M. H., Borjali, A., Professor, D. O. C. P., Abolghasemi, S., Assistant Professor, D. O. I. M., Hassanabadi, H. R., & Associate Professor, D. O. E. P. (2022) · Avicenna Journal of Clinical Medicine · doi:10.52547/ajcm.28.4.244 · Cited by 1 · see citing works
Cohen-Biton, L., Buskila, D., & Gannot, R. N. (2024) · BioMed · doi:10.3390/biomed4020006 · Cited by 1 · see citing works
“FM is associated with neurosensitivity and reduced conditioned pain modulation (CPM) [9].”
BackgroundEffects of connective tissue massage and kinesiotaping in patients with fibromyalgia
Turksen, G., Kısa, E. P., Kaya, B. K., Muammer, K., & Muammer, R. (2024) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2024.07.009 · Cited by 2 · see citing works
The medico-legal pertinence of musculoskeletal nociplastic pain
Fitzcharles, M., & Assis, R. D. (2025) · Medico-Legal Journal · doi:10.1177/00258172241285986 · Cited by 1 · see citing works
Shtoots, L., Halpert, G., Partouche, R., Levy, D. A., Amital, H., & Shoenfeld, Y. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149980 · Cited by 1 · see citing works
Bertin, C., Dupouy, J., Authier, N., Michenot, N., Verdier, S., Chappuy, M., & Trouvin, A. (2026) · Pain and Therapy · doi:10.1007/s40122-026-00853-8 · Cited by 2 · see citing works
Santos, T. C. A., Gomes, I. A., & Menezes, P. D. P. (2022) · Research Society and Development · doi:10.33448/rsd-v11i9.31684 · Cited by 1 · see citing works
Intervenciones farmacológicas en fibromialgia; consideraciones actuales
Gálvez, L. A., & Vega, D. A. M. (2022) · Revista de la Sociedad Española del Dolor · doi:10.20986/resed.2022.4001/2022 · Cited by 1 · see citing works
Chronic Neuropathic Pain: Fibromyalgia
Miedany, Y. M. E. (2022) · Contemporary rheumatology · doi:10.1007/978-3-031-10687-3_11 · Cited by 1 · see citing works
Fibromialgia e disfunção temporomandibular: uma revisão de escopo
Bosco, T. D., Torres, I. L. D. S., Stein, D. J., & de Oliveira, F. F. (2023) · Clinical & Biomedical Research · doi:10.22491/2357-9730.128039 · Cited by 2 · see citing works
Das Fibromyalgiesyndrom als Schmerzsyndrom in der Rheumatologie
Krasselt, M., & Baerwald, C. (2023) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-1965-6870 · Cited by 1 · see citing works
“Frü-her durchgeführte Untersuchungen erbrachten zum Teil widersprüchliche Ergebnisse [24].”
BackgroundVilalta‐Abella, F., Porras-García, B., Ghiţă, A., Vacas, M., Prat, M., & Gutiérrez‐Maldonado, J. (2023) · British Journal of Pain · doi:10.1177/20494637231210391 · Cited by 1 · see citing works
Effect of Steroids on Patients With Fibromyalgia/Chromic Widespread Pain: An Observational Study
Gurunathan, O. S., Eswaradass, C., Thirunavukkarasu, S., Thermalingem, S., & Eswaradass, P. V. (2024) · Cureus · doi:10.7759/cureus.53736 · Cited by 1 · see citing works
Imamura, M., Robertson, C., Hudson, J., Whibley, D., Aucott, L. S., Gillies, K., Beasley, M., Stevens, M., Manson, P. D., Dulake, D., et al. (2025) · Health Technology Assessment · doi:10.3310/gtbr7561 · Cited by 2 · see citing works
Prevalence, Diagnostic Challenges and Management of Fibromyalgia
Baoum, S. O., AlShaikh, S., Albaqsh, N., AlAmry, S., AlHussain, M., Almehmadi, A., Al-Asmari, Y. A., Albeetar, W. M., Azi, N., Alkathiri, O., et al. (2023) · Journal of Healthcare Sciences · doi:10.52533/johs.2023.30108 · Cited by 1 · see citing works
Understanding Fibromyalgia 2020
Schreibman, C. (2020) · Physician Assistant Clinics · doi:10.1016/j.cpha.2020.09.002
Kalcev, G., Testa, G., Manconi, M., Bacchetta, G., Scano, A., Orrù, G., Deidda, M. C., Finco, G., & Carta, M. G. (2020) · Biointerface Research in Applied Chemistry · doi:10.33263/briac113.99289938
Alves, M. F., Silva, A. B. D. B., Ferreira, K. G., Cruz, B. G. R., Machado, L. C. D. S., de Souza, M. C. M. C., Júdice, M. G., & da Silva, R. C. D. (2020) · Journal Health NPEPS
Comborbid fibromyalgia with depression in geriatric
Natanael, R. J. M., Diniari, N. K. S., & Kuswardhani, R. A. T. (2022) · International journal of health & medical sciences · doi:10.21744/ijhms.v5n4.1996
Fibromyalgia in the light of different methods of treatment
Szota, M., Modlińska, A., Rogacka, K., & Kędziora–Kornatowska, K. (2022) · Journal of Education Health and Sport · doi:10.12775/jehs.2022.12.12.050
“Endokannabinoidy uwalniane są na skutek depolaryzacji komórek, a ich obecność prowadzi do pobudzenia receptora CB1, który hamuje presynaptyczne przekaźnictwo GABA-ergiczne i glutaminergiczne [13].”
BackgroundKhaliq, R. Z., Manzoor, Y., Shehzad, M., & Zaman, T. (2022) · International Journal of Natural Medicine and Health Sciences · doi:10.52461/ijnms.v2i1.1366
Pharmacologic Treatment Options in Functional Illness
Abijay, C. A., & Agan, A. D. (2023) · Springer eBooks · doi:10.1007/978-3-031-12998-8_20
Pain makes me anxious, and anxiety gives me pain
Jackson, D., & Pal, S. (2024) · Cambridge University Press eBooks · doi:10.1017/9781108623872.017
- Authors
- Tzadok, R., & Ablin, J. N.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Tzadok, Roie
- Venue
- Pain Research and Management
- Publisher
- Wiley
- Published
- 2020-02-11
- Volume
- 2020
- Pages
- 1-9
- ISSN
- 1203-6765 (ISSN-L)
- 1918-1523
- PMC
- PMC7036118
- OpenAlex
- W3005953215
- Cited by
- 122
- References
- 86
- Citations by year
- 2026: 7 · 2025: 24 · 2024: 25 · 2023: 23 · 2022: 24 · 2021: 13 · 2020: 6
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Pain Research and Management (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- fibromyalgia, pharmacotherapy, pregabalin, duloxetine, milnacipran, conditioned pain modulation, cognitive impairment, pain processing, cannabinoid therapy, opioid therapy, personalized treatment, functional imaging
- MeSH terms
- Analgesics, Female, Fibromyalgia, Humans, Chronic Pain, Pain Management
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