Fibromyalgie: wetenschappelijke onderzoek

Het protocol voor de behandeling fibromyalgie is op basis van wetenschappelijke publicaties ontwikkeld. Hierbij is gebruik gemaakt van hoog gekwalificerd recent onderzoek dat wordt gepubliceerd in de PubMed database. placebo controlled onderzoek, meta analyses en reviews hebben de voorkeur. Dit soort onderzoek valt onder Evidence Based Medicine.

Pathologie van fibromaylgie

Centrale zenuwgestel



REVIEW

1. Staud R, Spaeth M. CNS Spectr. 2008 Mar;13(3 Suppl 5):12-7. Psychophysical and neurochemical abnormalities of pain processing in fibromyalgia
   Many recent fibromyalgia studies have demonstrated central nervous system (CNS) pain processing abnormalities, including abnormal temporal summation of pain.[/fusion_builder_column]
   [Abstract]
2. Gur A, Oktayoglu P. Curr Pharm Des. 2008;14(13):1274-94. Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment
   Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are poorly understood disorders that share similar demographic and clinical characteristics. The etiology and pathophysiology of these diseases remain unclear. Because of the similarities between both disorders it was suggested that they share a common pathophysiological mechanisms, namely, central nervous system (CNS) dysfunction.[Abstract]

STUDY

3. M. Petroua, R.E. Harrisb, B.R. Foerstera, S.A. Mcleanc, A. Send, D.J. Clauwb and P.C. Sundgrena PC AJNR Am J Neuroradiol. 2008 May;29(5):913-8. doi: 10.3174/ajnr.A0959. Epub 2008 Mar 13. Proton MR Spectroscopy in the Evaluation of Cerebral Metabolism in Patients with Fibromyalgia: Comparison with Healthy Controls and Correlation with Symptom Severity
   Widespread pain sensitivity in patients with fibromyalgia (FM) suggests a central nervous system (CNS)-processing problem.[Article]
4. Emad Y, Ragab Y, Zeinhom F, El-Khouly G, Abou-Zeid A, Rasker JJ. Hippocampus dysfunction may explain symptoms of fibromyalgia syndrome. A study with single-voxel magnetic resonance spectroscopy
   The hippocampus was dysfunctional in patients with FM, as shown by lower NAA levels compared to controls, representing neuronal or axonal metabolic dysfunction. As the hippocampus plays crucial roles in maintenance of cognitive functions, sleep regulation, and pain perception, we suggest that metabolic dysfunction of hippocampus may be implicated in the appearance of these symptoms associated with this puzzling syndrome.[Abstract]

Slaapstoornissen

REVIEW

5. Spaeth M, Rizzi M, Sarzi-Puttini P. Best Pract Res Clin Rheumatol. 2011 Apr;25(2):227-39. doi: 10.1016/j.berh.2011.03.004. Fibromyalgia and sleep
   Chronic pain in fibromyalgia patients, together with its associated symptoms and co-morbidities, is now considered a result of dysregulated mechanisms in the central nervous system (CNS). As fibromyalgia patients often report sleep problems, the physiological processes that normally regulate sleep may be disturbed and overlap with other CNS dysfunctions.[Abstract]
6. Moldofsky H. CNS Spectr. 2008 Mar;13(3 Suppl 5):22-6. The significance, assessment, and management of nonrestorative sleep in fibromyalgia syndrome
   People with fibromyalgia syndrome (FMS) experience unrefreshing sleep, aches, hypersensitivity, and cognitive and emotional difficulties. Although no specific causative factor or biological agent is known to account for all of the features of FMS and these related diagnoses, the generalized hypersensitivity of the body is considered to be affected by disturbances in central nervous system (CNS) functions.[Abstract]
7. Prados G, Miro E. Rev Neurol. 2012 Feb 16;54(4):227-40. Fibromyalgia and sleep: a review
   The importance of sleep in this syndrome is increasingly being understood thanks to the progress made in research on fibromyalgia and the use of biopsychosocial explanatory models. Many studies have shown complex inter-actions between sleep disturbances, neuroendocrine and immune abnormalities and the clinical symptoms present in fibromyalgia.[Abstract]
8. Roizenblatt S, Neto NS, Tufik S. Curr Pain Headache Rep. 2011 Oct;15(5):347-57. doi: 10.1007/s11916-011-0213-3. Sleep disorders and fibromyalgia
   Disordered sleep is such a prominent symptom in fibromyalgia that the American College of Rheumatology included symptoms such as waking unrefreshed, fatigue, tiredness, and insomnia in the 2010 diagnostic criteria for fibromyalgia.[Abstract]

Serotoninestoornis

REVIEW

9. Juhl JH. Altern Med Rev. 1998 Oct;3(5):367-75. Fibromyalgia and the serotonin pathway
   Fibromyalgia syndrome is a musculoskeletal pain and fatigue disorder manifested by diffuse myalgia, localized areas of tenderness, fatigue, lowered pain thresholds, and nonrestorative sleep. Evidence from multiple sources support the concept of decreased flux through the serotonin pathway in fibromyalgia patients. Serotonin substrate supplementation, via L-tryptophan or 5-hydroxytryptophan (5-HTP), has been shown to improve symptoms of depression, anxiety, insomnia and somatic pains in a variety of patient cohorts. Identification of low serum tryptophan and serotonin levels may be a simple way to identify persons who will respond well to this approach.[Article]

STUDY

10. Frank B, Niesler B, Bondy B, Späth M, Pongratz DE, Ackenheil M, Fischer C, Rappold G. Clin Rheumatol. 2004 Aug;23(4):338-44. Epub 2004 May 7. Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients
    Dysfunction of serotonergic neurotransmission is thought to play a major role in the pathophysiology of the fibromyalgia syndrome (FMS) which is characterised by non-restorative sleep and severe pain.[Abstract]

Tekorten aan bio-energie

REVIEW

11. Le Goff P. Joint Bone Spine. 2006 May;73(3):239-42. Epub 2005 Nov 9. Is fibromyalgia a muscle disorder?
    Biochemical studies and P 31 magnetic resonance spectroscopy show inconstant abnormalities of ATP and phosphocreatine levels. Mitochondrial abnormalities reduced capillary circulation and thickened capillary endothelium may result in decreased availability of oxygen and impaired oxidative phosphorylation as well as ATP synthesis.[Abstract]
12. Bengtsson A, Henriksson KG. J Rheumatol Suppl. 1989 Nov;19:144-9. The muscle in fibromyalgia–a review of Swedish studies
    These studies have shown changes indicating disturbed microcirculation, mitochondrial damage and a reduced content of high energy phosphates. Thus, there may be an energy deficiency state in the resting painful muscle in fibromyalgia.[Abstract]
13. Cordero MD, de Miguel M, Carmona-López I, Bonal P, Campa F, Moreno-Fernández AM. Neuro Endocrinol Lett. 2010;31(2):169-73 Oxidative stress and mitochondrial dysfunction in fibromyalgia
    Recently have been showed CoQ10 deficiency in blood mononuclear cells in FM patients, so if the hypothesis that mitochondrial dysfunction is the origin of oxidative stress in FM patients is demonstrated, could help to understand the complex pathophysiology of this disorder and may lead to development of new therapeutic strategies for prevention and treatment of this disease.[Abstract]

STUDY

14. Bazzichi L, Giannaccini G, Betti L, Fabbrini L, Schmid L, Palego L, Giacomelli C, Rossi A, Giusti L, De Feo F, Giuliano T, Mascia G, Bombardieri S, Lucacchini A. Clin Biochem. 2008 Sep;41(13):1084-90. doi: 10.1016/j.clinbiochem.2008.06.012. Epub 2008 Jul 2. ATP, calcium and magnesium levels in platelets of patients with primary fibromyalgia
    This preliminary study suggests that disturbances in the homeostasis of platelet ATP metabolism-signaling and calcium-magnesium flows might have a relevance in the pathogenesis of FMs.[Abstract]

Stress

REVIEW

15. Van Houdenhove B, Luyten P. Acta Neurol Belg. 2006 Dec;106(4):149-56.
    There is increasing evidence that stress and depression may play a crucial role in the aetiology and pathophysiology of fibromyalgia (FM).[Abstract]
16. Van Houdenhove B, Egle UT. Psychother Psychosom. 2004 Sep-Oct;73(5):267-75. Fibromyalgia: a stress disorder? Piecing the biopsychosocial puzzle together
    Although the exact aetiology and pathogenesis of FM are still unknown, it has been suggested that stress may play a key role in the syndrome.[Abstract]
17. Lyon P, Cohen M, Quintner J. Pain Med. 2011 Aug;12(8):1167-78. doi: 10.1111/j.1526-4637.2011.01168.x. An evolutionary stress-response hypothesis for chronic widespread pain (fibromyalgia syndrome)
    Drawing on diverse findings in neurobiology, immunology, physiology, and comparative biology, we suggest that the form of central sensitization that leads to the profound phenomenological features of chronic widespread pain is part of a whole-organism stress response, which is evolutionarily conserved, following a general pattern found in the simplest living systems.[Abstract]

Genetische predispositie

18. Buskila D, Sarzi-Puttini P, Ablin JN. Pharmacogenomics. 2007 Jan;8(1):67-74. The genetics of fibromyalgia syndrome
    The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS.[Abstract]
19. Buskila D, Sarzi-Puttini P. Arthritis Res Ther. 2006;8(5):218. Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome
    Genetic and environmental factors may play a role in the etiopathology of fibromyalgia syndrome (FMS) and other related syndromes. There is a high aggregation of FMS in families of FMS patients.[Article]
20. Buskila D, Neumann L. Curr Pain Headache Rep. 2005 Oct;9(5):313-5. Genetics of fibromyalgia
    The pathogenesis of fibromyalgia (FM) and related conditions is not entirely understood. Recent evidence suggests that these syndromes may share heritable pathophysiologic features. Familial studies suggest that genetic and familial factors may play a role in the etiopathogenesis of these conditions.[Abstract]
21. Ablin JN, Cohen H, Buskila D. Nat Clin Pract Rheumatol. 2006 Dec;2(12):671- Mechanisms of Disease: genetics of fibromyalgi
    Fibromyalgia is characterized by widespread pain and tenderness, and has a significant familial component.[Abstract]

Tekorten aan aminozuren

22. Bazzichi L, Palego L, Giannaccini G, Rossi A, De Feo F, Giacomelli C, Betti L, Giusti L, Mascia G, Bombardieri S, Lucacchini A. Clin Biochem. 2009 Jul;42(10-11):1064-70. doi: 10.1016/j.clinbiochem.2009.02.025. Epub 2009 Mar 10. Altered amino acid homeostasis in subjects affected by fibromyalgia
    Our results suggest probable defects of gut malabsorption of certain AAs in FM patients. Moreover, given the reduced Tyr CAA’ ratio in FM patients, a possible impairment of the cathecolaminergic system in the FM syndrome may be suggested.[Abstract]
23. Maes M, Verkerk R, Delmeire L, Van Gastel A, van Hunsel F, Scharpé S. Psychiatry Res. 2000 Dec 4;97(1):11-20. Serotonergic markers and lowered plasma branched-chain-amino acid concentrations in fibromyalgia
    Patients with fibromyalgia had significantly lower plasma concentrations of the three BCAAs (valine, leucine and isoleucine) and phenylalanine than normal controls. It is hypothesized that the relative deficiency in the BCAAs may play a role in the pathophysiology of fibromyalgia, since the BCAAs supply energy to the muscle and regulate protein synthesis in the muscles.[Abstract]

Tekorten aan mineralen

24. Sendur OF, Tastaban E, Turan Y, Ulman C. Rheumatol Int. 2008 Sep;28(11):1117-21. doi: 10.1007/s00296-008-0593-9. Epub 2008 May 22. The relationship between serum trace element levels and clinical parameters in patients with fibromyalgia
    Serum levels of zinc (P = 0.001) and magnesium (P = 0.002) were significantly decreased by FM groups, whereas there was no considerable difference with selenium levels of both groups (P > 0.05). Association between serum zinc level and number of tender points (P = 0.008) and that between fatigue and magnesium level (P = 0.003) was found as meaningful. According to the results of this study, it was asserted that serum magnesium and zinc levels may play an important role in the pathophysiology of FM.[Abstract]
25. Eisinger J, Plantamura A, Marie PA, Ayavou T. Magnes Res. 1994 Dec;7(3-4):285-8.
    Selenium and magnesiu Selenium and magnesium status in fibromyalgia
    Muscle pain has been associated with magnesium (Mg) and selenium (Se) deficiency: magnesium and selenium status were investigated in fibromyalgia (FM).[Abstract]
26. Reinhard P, Schweinsberg F, Wernet D, Kötter I. Toxicol Lett. 1998 Aug;96-97:177-80. Selenium status in fibromyalgia
    There was a statistical significant difference (P < 0.05) in serum Se between control (median 77 microg/l; range: 50-118 microg/l) and patients (median 71 microg/l; range: 39-154 microg/l) groups in the region of Tübingen, Germany.[Abstract]

Tekorten aan vitamine D

27. Olama SM, Senna MK, Elarman MM, Elhawary G. Rheumatol Int. 2013 Jan;33(1):185-92. doi: 10.1007/s00296-012-2361-0. Serum vitamin D level and bone mineral density in premenopausal Egyptian women with fibromyalgia
    This study confirmed high prevalence of hypovitaminosis D among in patients with PFMS.[Abstract]
28. Bhatty SA, Shaikh NA, Irfan M, Kashif SM, Vaswani AS, Sumbhai A, Gunpat. J Pak Med Assoc. 2010 Nov;60(11):949-51. Vitamin D deficiency in fibromyalgia
    itamin D deficiency is frequently seen in patients diagnosed as fibromyalgia and nonspecific musculoskeletal pain in our population. Although the sample size of the study is small, but the figures are so alarming that it is an eye opener towards the need of a population based study, including normal population as well as those presenting with musculoskeletal pain.[Abstract]

REVIEW

29. Gerwin RD. Acupunct Med. 2005 Sep;23(3):121-34. A review of myofascial pain and fibromyalgia–factors that promote their persistence
    Precipitating or perpetuating causes of chronic myalgia include structural or mechanical causes like scoliosis, localised joint hypomobility, or generalised or local joint laxity; and metabolic factors like depleted tissue iron stores, hypothyroidism or Vitamin D deficiency. Sometimes, correction of an underlying cause of myalgia is all that is needed to resolve the condition.[Article]
30. 
    .[Abstract]

Verwante stoornissen

31. Buskila D, Odes LR, Neumann L, Odes HS. J Rheumatol. 1999 May;26(5):1167-71. Fibromyalgia in inflammatory bowel diseas
    FM is common in IBD, particularly Crohn’s disease. The lower pain threshold in Crohn’s disease may suggest a disease-specific effect. Recognizing FM in patients with IBD will prevent misdiagnosis and ensure correct treatment.[Abstract]
32. Ifergane G, Buskila D, Simiseshvely N, Zeev K, Cohen H. Cephalalgia. 2006 Apr;26(4):451-6. Prevalence of fibromyalgia syndrome in migraine patients
    A high incidence of FMS was found among female migraine patients but not in males.[Abstract]

OTHER

33. Rodrigo L, Blanco I, Bobes J, de Serres FJ. Arthritis Res Ther. 2013;15(6):R201. Remarkable prevalence of coeliac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study
    The findings of this screening indicate that a non-negligible percentage of IBS/FMS patients are CD patients, whose symptoms can improve and in whom long-term CD-related complications might possibly be prevented with a strict lifelong GFD.[Article]

Behandeling van fibromaylgie

META

1. Häuser W, Bernardy K, Uçeyler N, Sommer C. JAMA. 2009 Jan 14;301(2):198-209. doi: 10.1001/jama.2008.944. Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis
   Antidepressant medications are associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related quality of life in patients with FMS.[Article]

Amitriptyline

META

2. Häuser W, Wolfe F, Tölle T, Uçeyler N, Sommer C. CNS Drugs. 2012 Apr 1;26(4):297-307. doi: 10.2165/11598970-000000000-00000. The role of antidepressants in the management of fibromyalgia syndrome: a systematic review and meta-analysis
   The TCA amitriptyline and the SNRIs duloxetine and milnacipran are first-line options for the treatment of FMS patients. Physicians and patients should be realistic about the potential benefits of antidepressants in FMS. A small number of patients experience a substantial symptom relief with no or minor adverse effects. However, a remarkable number of patients dropout of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects.[Abstract]

REVIEW

3. Uçeyler N, Häuser W, Sommer C. Arthritis Rheum. 2008 Sep 15;59(9):1279-98. doi: 10.1002/art.24000. A systematic review on the effectiveness of treatment with antidepressants in fibromyalgia syndrome
   Amitriptyline 25-50 mg/day reduces pain, fatigue, and depressiveness in patients with FMS and improves sleep and quality of life. [Abstract]

Duloxetine

META

4. Sommer C, Häuser W, Alten R, Petzke F, Späth M, Tölle T, Uçeyler N, Winkelmann A, Winter E, Bär KJ; Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften. Schmerz. 2012 Jun;26(3):297-310. doi: 10.1007/s00482-012-1172-2. Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline
   Amitriptyline and-in case of comorbid depressive disorder or generalized anxiety disorder-duloxetine are recommended.[Abstract]

RCT

5. Arnold LM, Lu Y, Crofford LJ, Wohlreich M, Detke MJ, Iyengar S, Goldstein DJ. Arthritis Rheum. 2004 Sep;50(9):2974-84. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder
   In this randomized, controlled, 12-week trial (with a 1-week placebo lead-in phase), duloxetine was an effective and safe treatment for many of the symptoms associated with fibromyalgia in subjects with or without major depressive disorder, particularly for women, who had significant improvement across most outcome measures.[Article]

Pregabaline

META

6. Arnold LM, Emir B, Murphy TK, Zeiher BG, Pauer L, Scott G, Petersel D. Clin Ther. 2012 May;34(5):1092-102. doi: 10.1016/j.clinthera.2012.03.003. Safety profile and tolerability of up to 1 year of pregabalin treatment in 3 open-label extension studies in patients with fibromyalgia
   The data from these extension studies suggest that the adverse event safety profile and tolerability of patients with FM treated with open-label pregabalin (75-300 mg BID) for up to 1 year were stable and were consistent with those of previous studies.[Abstract]
7. Roskell NS, Beard SM, Zhao Y, Le TK. Pain Pract. 2011 Nov-Dec;11(6):516-27. doi: 10.1111/j.1533-2500.2010.00441.x. Epub 2010 Dec 28. A meta-analysis of pain response in the treatment of fibromyalgia
   When compared with placebo, statistically significant pain responses (improvement of 30% and 50%) were observed for patients treated with duloxetine, milnacipran 200 mg/day, pregabalin 300 or 450 mg/day, and tramadol plus paracetamol. Treatment with fluoxetine, gabapentin, or milnacipran 100 mg/day resulted in significant findings for the 30% improvement in pain response.[Abstract]
8. Tzellos TG, Toulis KA, Goulis DG, Papazisis G, Zampeli VA, Vakfari A, Kouvelas D. J Clin Pharm Ther. 2010 Dec;35(6):639-56. doi: 10.1111/j.1365-2710.2009.01144.x. Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis
   The analysis indicates that PB at a dose of 450 mg per day is most likely effective in treating FBM, although AE are not negligible.[Article]
9. Straube S, Derry S, Moore RA, Paine J, McQuay HJ. BMC Musculoskelet Disord. 2010 Jul 5;11:150. doi: 10.1186/1471-2474-11-150. Pregabalin in fibromyalgia–responder analysis from individual patient data
   Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time.[Article]
10. Häuser W, Petzke F, Sommer C. J Pain. 2010 Jun;11(6):505-21. doi: 10.1016/j.jpain.2010.01.002. Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome
    Significant differences in average symptom reduction were found: DLX and PGB were superior to MLN in reduction of pain and sleep disturbances. DLX was superior to MLN and PGB in reducing depressed mood. MLN and PGB were superior to DLX in reducing fatigue. The risk of headache and nausea with DLX and MLN was higher compared with PGB. The risk of diarrhea was higher with DLX compared to MLN and PGB.[Abstract]
11. Straube S, Derry S, Moore RA, McQuay HJ. Rheumatology (Oxford). 2010 Apr;49(4):706-15. doi: 10.1093/rheumatology/kep432. Pregabalin in fibromyalgia: meta-analysis of efficacy and safety from company clinical trial reports
    Pregabalin is effective in treating FM and is relatively safe.[Article]
12. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007076. doi: 10.1002/14651858.CD007076.pub2. Pregabalin for acute and chronic pain in adults
    Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events.[Abstract]
13. Häuser W, Bernardy K, Uçeyler N, Sommer C. Pain. 2009 Sep;145(1-2):69-81. doi: 10.1016/j.pain.2009.05.014. Treatment of fibromyalgia syndrome with gabapentin and pregabalin–a meta-analysis of randomized controlled trials
    There was strong evidence for a reduction of pain, improved sleep, and improved health-related quality of life, but not for depressed mood. There was strong evidence for a non-substantial reduction of fatigue and of anxiety.[Abstract]

milnacipran

CLINICAL

14. Arnold LM1, Palmer RH, Ma Y. Clin J Pain. 2013 Dec;29(12):1021-8. doi: 10.1097/AJP.0b013e31828440ab. A 3-year, open-label, flexible-dosing study of milnacipran for the treatment of fibromyalgia
15. 
    In all patient cohorts, these improvements were observed by month 3 and remained relatively constant over time. At final study visit in the 3-year cohort, 70.3% of patients rated their overall fibromyalgia as “much improved” or “very much improved.[Abstract]
16. 
    .[Abstract]

5-HTP

REVIEW

17. Altern Med Rev. 1998 Jun;3(3):224-6. 5-hydroxytryptophan
    .[Article]
18. Birdsall TC. Altern Med Rev. 1998 Aug;3(4):271-80. 5-Hydroxytryptophan: a clinically-effective serotonin precursor
    5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness.[Article]
19. Turner EH, Loftis JM, Blackwell AD. Pharmacol Ther. 2006 Mar;109(3):325-38. Epub 2005 Jul 14. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan
    Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome.[Abstract]
20. Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V. J Int Med Res. 1990 May-Jun;18(3):201-9. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome
    A double-blind, placebo-controlled study of the efficacy and tolerability of 5-hydroxytryptophan (5-HTP) was conducted in 50 patients with primary fibromyalgia syndrome. All the clinical parameters studied were significantly improved by treatment with 5-HTP and only mild and transient side-effects were reported. Further controlled studies are required to define properly the value of 5-HTP in patients with primary fibromyalgia syndrome.[Abstract]

STUDY

21. Sarzi Puttini P, Caruso I. J Int Med Res. 1992 Apr;20(2):182-9. Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study
    It is concluded that 5-HTP is effective in improving the symptoms of primary fibromyalgia syndrome and that it maintains its efficacy throughout the 90-day period of treatment.[Abstract]

CLINICAL TRIAL

22. Nicolodi M, Sicuteri F. Adv Exp Med Biol. 1996;398:373-9. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy
    Enhancing serotonergic analgesia while increasing adrenergically mediated analgesia seems to be an important tool in fibromyalgia. Treatment consisting with the association MAOIs/5-HTP is aimed at enhancing serotonergic/adrenergic transmission by inducing an up-regulation of serotonergic/adrenergic receptors and a simultaneous increase of serotonin levels in the central nervous .[Abstract]

Hypericum

META

23. Rahimi R, Nikfar S, Abdollahi M Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):118-27. doi: 10.1016/j.pnpbp.2008.10.018. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis
    Hypericum does not differ from SSRIs according to efficacy and adverse events in MDD. Lower withdrawal from study due to adverse events by Hypericum is an advantage in management of MDD.[Abstract]

REVIEW

24. Müller WE. Pharmacol Res. 2003 Feb;47(2):101-9. Current St John’s wort research from mode of action to clinical efficacy
    In summary, pharmacological activity and therapeutic efficacy of St. John’s wort extract as an antidepressant are supported by a large number of scientific publications.[Abstract]

STUDY

25. Olajide OA. J Diet Suppl. 2009;6(1):28-32. doi: 10.1080/19390210802687247. Inhibitory effects of St. John’s Wort on inflammation: ignored potential of a popular herb
    Although not commonly known for this use, St John’s wort is also reputed for its usefulness in inflammatory conditions such as sciatica and fibromyalgia.[Abstract]
26. Laakmann G, Jahn G, Schüle C. Nervenarzt. 2002 Jul;73(7):600-12. Hypericum perforatum extract in treatment of mild to moderate depression. Clinical and pharmacological aspects
    Hypericum extracts can be regarded as well tolerated, and they extend the variety of pharmacotherapeutical options in the treatment of depression, especially in outpatients. However, interactions in combination treatments are possible by interference with the cytochrom P450 system, thereby changing plasma levels of other medications.[Abstract]

Vitamine D

27. Abokrysha NT. Pain Med. 2012 Mar;13(3):452-8. doi: 10.1111/j.1526-4637.2011.01304.x. Vitamin D deficiency in women with fibromyalgia in Saudi Arabia
    Effective treatment with high-dose vitamin D could lead to resolution of almost all symptoms. Further study of these populations and fortification of foods with vitamin D may be essential.[Abstract]

REVIEW

28. importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar;79(3):362-71. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis
    Vitamin D deficiency is often misdiagnosed as fibromyalgia. .[Article]

CLINICAL TRIAL

29. Matthana MH. Saudi Med J. 2011 Sep;32(9):925-9. The relation between vitamin D deficiency and fibromyalgia syndrome in women
    Among the 100 fibromyalgia women, there were 61 women with 25(OH) D deficiency; with vitamin D supplementation, only 42 women showed a significant improvement when their blood level of 25(OH) D became>or=30 ng/mL, this improvement became more significant when their blood level of 25(OH) D exceeded 50 ng/ mL. Vitamin D deficiency has to be considered in the management of fibromyalgia syndrome. [Abstract]

Myers’ Cocktail

30. From Wikipedia, the free encyclopedia Myers’ cocktail
    “Myers’ cocktail” is the colloquial name for an intravenous nutrient mixture invented by Baltimore physician John Myers containing magnesium, calcium, various B vitamins and vitamin C that is promoted as an alternative treatment for a broad range of conditions. It is included in Quackwatch’s index of questionable treatments.[1] Evidence to support its use is largely anecdotal with very few scientific publications supporting its use.[Article]

RCT

31. Ali A, Njike VY, Northrup V, Sabina AB, Williams AL, Liberti LS, Perlman AI, Adelson H, Katz DL. J Altern Complement Med. 2009 Mar;15(3):247-57. doi: 10.1089/acm.2008.0410. Intravenous micronutrient therapy (Myers’ Cocktail) for fibromyalgia: a placebo-controlled pilot study
    This first controlled pilot study established the safety and feasibility of treating FMS with IVMT. Most subjects experienced relief as compared to baseline.[Article]
32. Russell IJ, Michalek JE, Flechas JD, Abraham GE. J Rheumatol. 1995 May;22(5):953-8. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study
    These data suggest that Super Malic is safe and may be beneficial in the treatment of patients with FM. Future placebo-controlled studies should utilize up to 6 tablets of Super Malic bid and continue therapy for at least 2 months.[Abstract]

CLINICAL TRIAL

33. Massey PB. Altern Ther Health Med. 2007 May-Jun;13(3):32-4. Reduction of fibromyalgia symptoms through intravenous nutrient therapy: results of a pilot clinical trial
    IVNT appears to be safe to reduce FM symptoms.[Abstract]
34. Gaby AR. Altern Med Rev. 2002 Oct;7(5):389-403. Intravenous nutrient therapy: the “Myers’ cocktail”
    The modified “Myers’ cocktail,” which consists of magnesium, calcium, B vitamins, and vitamin C, has been found to be effective against acute asthma attacks, migraines, fatigue (including chronic fatigue syndrome), fibromyalgia, acute muscle spasm, upper respiratory tract infections, chronic sinusitis, seasonal allergic rhinitis, cardiovascular disease, and other disorders.[Article]



Magnesium

REVIEW

35. Porter NS, Jason LA, Boulton A, Bothne N, Coleman B. J Altern Complement Med. 2010 Mar;16(3):235-49. doi: 10.1089/acm.2008.0376. Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia
    Likewise, magnesium, l-carnitine, and S-adenosylmethionine are nonpharmacological supplements with the most potential for further research.[Abstract]

D-Ribose

REVIEW

36. Gilula MF. Expert Rev Med Devices. 2007 Jul;4(4):489-95. Cranial electrotherapy stimulation and fibromyalgia
    D-ribose supplementation may prove to significantly enhance energy, sleep, mental clarity, pain control and well-being in FM patients.[Abstract]

CLINICAL TRIAL

37. Teitelbaum JE, Johnson C, St Cyr J J Altern Complement Med. 2006 Nov;12(9):857-62. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study
    D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome.[Abstract]

STUDY

38. Gebhart B, Jorgenson JA. Pharmacotherapy. 2004 Nov;24(11):1646-8. Benefit of ribose in a patient with fibromyalgia
    Ribose was added to the existing treatment regimen of a woman with fibromyalgia, resulting in a decrease in symptoms.[Abstract]

CoQ10

RCT

39. Miyamae T, Seki M, Naga T, Uchino S, Asazuma H, Yoshida T, Iizuka Y, Kikuchi M, Imagawa T, Natsumeda Y, Yokota S, Yamamoto Y. Redox Rep. 2013;18(1):12-9. doi: 10.1179/1351000212Y.00000000 Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation
    Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.[Abstract]

CLINICAL TRIAL

40. Cordero MD, Alcocer-Gómez E, de Miguel M, Cano-García FJ, Luque CM, Fernández-Riejo P, Fernández AM, Sánchez-Alcazar JA. Mitochondrion. 2011 Jul;11(4):623-5. doi: 10.1016/j.mito.2011.03.122 Coenzyme Q(10): a novel therapeutic approach for Fibromyalgia? case series with 5 patients
    Patients with CoQ(10) deficiency showed a statistically significant reduction on symptoms after CoQ(10) treatment during 9 months (300 mg/day). Determination of deficiency and consequent supplementation in FM may result in clinical improvement. Further analysis involving more scientifically rigorous methodology will be required to confirm this observation.[Abstract]
41. Lister RE. J Int Med Res. 2002 Mar-Apr;30(2):195-9. An open, pilot study to evaluate the potential benefits of coenzyme Q10 combined with Ginkgo biloba extract in fibromyalgia syndrome
    A progressive improvement in the quality-of-life scores was observed over the study period and at the end, the scores showed a significant difference from those at the start. This was matched by an improvement in self-rating with 64% claiming to be better and only 9% claiming to feel worse.[Article]

REVIEW

42. Cordero MD, de Miguel M, Carmona-López I, Bonal P, Campa F, Moreno-Fernández AM. Neuro Endocrinol Lett. 2010;31(2):169-73 Oxidative stress and mitochondrial dysfunction in fibromyalgia
    Recently have been showed CoQ10 deficiency in blood mononuclear cells in FM patients, so if the hypothesis that mitochondrial dysfunction is the origin of oxidative stress in FM patients is demonstrated, could help to understand the complex pathophysiology of this disorder and may lead to development of new therapeutic strategies for prevention and treatment of this disease.[Abstract]

STUDY

43. Cordero MD, De Miguel M, Moreno Fernández AM, Carmona López IM, Garrido Maraver J, Cotán D, Gómez Izquierdo L, Bonal P, Campa F, Bullon P, Navas P, Sánchez Alcázar JA. Arthritis Res Ther. 2010;12(1):R17. doi: 10.1186/ar2918. Epub 2010 Jan 28. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease
    We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy.[Article]
44. Cordero MD, Moreno-Fernández AM, deMiguel M, Bonal P, Campa F, Jiménez-Jiménez LM, Ruiz-Losada A, Sánchez-Domínguez B, Sánchez Alcázar JA, Salviati L, Navas P. Clin Biochem. 2009 May;42(7-8):732-5. doi: 10.1016/j.clinbiochem.2008.12.010. Coenzyme Q10 distribution in blood is altered in patients with fibromyalgi
    The distribution of CoQ(10) in blood components was altered in FM patients. Also, our results confirm the oxidative stress background of this disease probably due to a defect on the distribution and metabolism of CoQ(10) in cells and tissues. The protection caused in mononuclear cells by CoQ(10) would indicate the benefit of its supplementation in FM patients.[Abstract]
45. Cordero MD, De Miguel M, Moreno Fernández AM, Carmona López IM, Garrido Maraver J, Cotán D, Gómez Izquierdo L, Bonal P, Campa F, Bullon P, Navas P, Sánchez Alcázar JA. Arthritis Res Ther. 2010;12(1):R17. doi: 10.1186/ar2918. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease
    We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients.[Article]

Melatonine

RCT

46. Hussain SA, Al-Khalifa II, Jasim NA, Gorial FI. J Pineal Res. 2011 Apr;50(3):267-71. doi: 10.1111/j.1600-079X.2010.00836.x. Adjuvant use of melatonin for treatment of fibromyalgia
    In conclusion, administration of melatonin, alone or in a combination with fluoxetine, was effective in the treatment of patients with FMS.[Abstract]
47. Citera G, Arias MA, Maldonado-Cocco JA, Lázaro MA, Rosemffet MG, Brusco LI, Scheines EJ, Cardinalli DP. Clin Rheumatol. 2000;19(1):9-13 The effect of melatonin in patients with fibromyalgia: a pilot study
    Although this is an open study, our preliminary results suggest that melatonin can be an alternative and safe treatment for patients with FM. Double-blind placebo controlled studies are needed.[Abstract]

REVIEW

48. Reiter RJ, Acuna-Castroviejo D, Tan DX. Curr Pain Headache Rep. 2007 Oct;11(5):339-4 Melatonin therapy in fibromyalgia
    Although melatonin is commonly known as a sleep aid (sleep/wake problems are common in FM sufferers), it has a variety of other beneficial effects that may account for its potential benefits in the treatment of FM.[Abstract]
49. Rohr UD, Herold J. Maturitas. 2002 Apr 15;41 Suppl 1:S85-104. Melatonin deficiencies in women
    It can be expected that melatonin will receive wide consideration for treatment of sleeping disturbances, jet lag, and fibromyalgia once an oral formulation becomes available in Europe.[Abstract]
50. Wilhelmsen M, Amirian I, Reiter RJ, Rosenberg J, Gögenur I. J Pineal Res. 2011 Oct;51(3):270-7. doi: 10.1111/j.1600-079X.2011.008 Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies
    In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). [Abstract]
51. Ambriz-Tututi M, Rocha-González HI, Cruz SL, Granados-Soto V. Life Sci. 2009 Apr 10;84(15-16):489-98. doi: 10.1016/j.lfs.2009.01.024. Melatonin: a hormone that modulates pain
    Melatonin receptors constitute attractive targets for developing analgesic drugs, and their activation may prove to be a useful strategy to generate analgesics with a novel mechanism of action.[Abstract]

STUDY

52. Wikner J, Hirsch U, Wetterberg L, Röjdmark S. Clin Endocrinol (Oxf). 1998 Aug;49(2):179- Fibromyalgia–a syndrome associated with decreased nocturnal melatonin secretion
    Patients with fibromyalgic syndrome have a lower melatonin secretion during the hours of darkness than healthy subjects. This may contribute to impaired sleep at night, fatigue during the day, and changed pain perception.[Abstract]

Carnitine

RCT

53. Rossini M, Di Munno O, Valentini G, Bianchi G, Biasi G, Cacace E, Malesci D, La Montagna G, Viapiana O, Adami S. Clin Exp Rheumatol. 2007 Mar-Apr;25(2):182-8. Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients
    Although this experience deserves further studies, these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients.[Article]

STUDY

54. Dupond JL, de Wazières B, Monnier G, Closs F, Desmurs H. Presse Med. 1992 Jun 6;21(21):974-8. Silent exercise-induced enzymatic myopathies at rest in adults. A cause of confusion with fibromyalgia
    Exercise-induced enzymatic myopathies include carnitine palmityl transferase deficiency and, among muscular glycogenoses, Mac Ardle’s and Tarui diseases. These diseases are usually recognized when exercise-induced myalgias, myoglobinuria and raised creatinine kinase (CK) levels are present.[Abstract]

MSM

REVIEW

55. Parcell Altern Med Rev. 2002 Feb;7(1):22-44. Sulfur in human nutrition and applications in medicine
    MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders.[Article]

Mindfulness

56. Fjorback LO. Dan Med J. 2012 Nov;59(11):B4547. Mindfulness and bodily distress
    In conclusion, the social and economic consequences of BDS are significant and mindfulness therapy may have a potential to significantly improve function, quality of life and symptoms, prevent a social decline, and reduce societal costs.[Abstract]
57. Merkes M. Aust J Prim Health. 2010;16(3):200-10. doi: 10.1071/PY09063. Mindfulness-based stress reduction for people with chronic diseases
    The studies included different research designs, and used self-report and physiological outcome measures. Participants’ clinical diagnoses included fibromyalgia, chronic pain, rheumatoid arthritis, type 2 diabetes, chronic fatigue syndrome, multiple chemical sensitivity, and cardiovascular diagnoses. All 15 studies found that participation in an MBSR program resulted in improvements.[Abstract]