Fibromiyalji Medikal Tedavi
Özet
Fibromiyalji sendromu (FMS), etiyopatogenezi tam olarak aydınlatılamamış, sistemik ve multidisipliner yaklaşım gerektiren kronik bir hastalıktır. Tedavinin temel hedefleri ağrı kontrolü, uyku kalitesinin artırılması, yorgunluk ve depresyonun giderilmesidir. FMS yönetiminde tek başına ilaç tedavilerinin klinik etkinliği sorgulanmakta olup, en iyi sonuçların farmakolojik ve non-farmakolojik yöntemlerin kombinasyonuyla elde edildiği belirtilmektedir. Tedavi protokollerinde monoterapi ve düşük dozlarla başlangıç önerilirken, amaca göre doz titrasyonu yapılmalıdır. Amerikan Gıda ve İlaç Dairesi (FDA) tarafından FMS tedavisinde kullanımı onaylanmış ajanlar pregabalin, duloksetin ve milnasiprandır. Klinik kılavuzlarda antiepileptikler (özellikle pregabalin), trisiklik antidepresanlar (amitriptilin) ve dual geri alım inhibitörleri (SNRI) orta ila güçlü kanıt düzeyleriyle ilk seçenekler arasında yer almaktadır. Buna karşın, hastalıkta enflamasyon bulunmadığı için nonsteroid antiinflamatuar ilaçların ve kortikosteroidlerin etkinliği sınırlıdır ve rutin kullanımı önerilmemektedir. Monoamin oksidaz inhibitörleri (MAOİ) ve siklobenzaprin gibi ajanlar ise yetersiz etkinlik veya ciddi yan etki profilleri nedeniyle kılavuzlarca dışlanmaktadır. Tedavi planlamasında hastaların semptom profili ve komorbid durumları mutlaka dikkate alınmalıdır.
Fibromyalgia syndrome (FMS) is a complex, systemic disorder with an incompletely understood pathophysiology, necessitating a personalized and multidisciplinary treatment approach. The primary therapeutic goals focus on pain management, enhancing sleep quality, and alleviating fatigue and depressive symptoms. Pharmacological monotherapy often demonstrates limited clinical efficacy; therefore, a combination of pharmacological interventions and non-pharmacological therapies is highly recommended for optimal outcomes. Current guidelines favor initiating treatment with low-dose monotherapy followed by gradual titration. Notably, pregabalin, duloxetine, and milnacipran are the only medications explicitly approved by the FDA for FMS treatment. Clinical evidence strongly supports the utilization of tricyclic antidepressants (specifically amitryptiline), serotonin-norepinephrine reuptake inhibitors (SNRIs like duloxetine and milnacipran), and certain antiepileptics (such as pregabalin) to address core symptoms. Conversely, because FMS lacks an inflammatory etiology, conventional analgesics, NSAIDs, and corticosteroids exhibit minimal effectiveness and are generally discouraged. Other investigated agents, including MAOIs, cyclobenzaprine, and various neuromodulators, are either not recommended or limited by their adverse effect profiles and lack of robust clinical data.
Referanslar
Bennett RM, Friend R, Marcus D, et al. Criteria for the diagnosis of fibromyalgia: validation of the modified 2010 preliminary ACR criteria and the development of alternative criteria. Arthritis Care Res (Hoboken). 2014 Sep;66(9):1364-73.
Demir, H., Fibromiyalji Sendromu, in Fiziksel Tıp ve Rehabilitasyon, M. Beyazova and Y.G. Kutsal, Editors. 2016, Güneş Kitabevi: Ankara. p. 1911-20.
Nuesch E, Hauser W, Bernardy K, Barth J, Juni P. Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis. Ann Rheum Dis. 2013;72:955-962.
Kia S, Choy E. Update on treatment guideline in fibromyalgia syndrome with focus on pharmacology. The Biomedicines 2017;5(20): doi:10.3390/biomedicines5020020.
Oncu J. Fibromiyalji sendromunda farmakolojik tedavi. Turkiye Klinikleri J PM&R-Special Topics 2015;8(3):28-35.
Sindel D, Saral İ, Esmaeilzadeh S. Fibromiyalji sendromunda uygulanan tedavi yontemleri. Turk Fiz Tıp Rehab Derg. 2012;58:136-42.
Calandre EP, Rico-Villademoros F, Rodriguez-Lopez CM. Monotherapy or combination therapy for fibromyalgia treatment? Curr Rheumatol Rep. 2012;14:568-575.
Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292:2388-2395.
Häuser W, Thieme K, Turk DC. Guidelines on the management of fibromyalgia syndrome - a systematic review.Eur J pain 2010; 14:5-10.
Halpern R, Shah SN, Cappelleri JC, Masters ET, Clair A. Evaluating guideline-recommended pain medication use among patients with newly diagnosed fibromyalgia. Pain Pract. 2015. doi:10.1111/papr.12364.
Calandre EP, Rico-Villademoros F, Slim M. An update on pharmacotherapy for the treatment of fibromyalgia. Expert Opin Pharmacother. 2015;16:1347–68. An updated review of current evidence for and against pharmacological treatment options for fibromyalgia.
Macfarlane GJ, Kronisch C, Dean LE, Atzeni F, Hauser W, Flus E, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318-328.
Choy E, Marshall D, Gabriel ZL, Mitchell SA, Gylee E, Dakin HA. A systematic review and mixed treatment comparison of the efficacy of pharmacological treatments for fibromyalgia. Semin Arthritis Rheum. 2011;41:335-345.
Derry S, Wiffen PJ, Hauser W, Mucke M, Tolle TR, Bell RF, Moore RA. Oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults. Cochrane Database of Systematic Reviews. 2017; Issue 3. Art. No.: CD012332.
Ngian G S, Guymer E K, Littlejohn G O, The use of opioids in fibromyalgia. Int J Rheum Dis, 2011; 6-11.
Goldenberg D L, Pharmacological treatment of fibromyalgia and other chronic musculoskeletal pain. Best Pract Res Clin Rheumatol, 2007; 499-511.
Schmidt-Wilcke T, Diers M. New insights into the pathophysiology and treatment of fibromyalgia. Biomedicines 2017;5(22): doi:10.3390/biomedicines5020022.
Hauser W, Petzke F, Uceyler N, Sommer C. Comparative efficacy and acceptability of amitriptyline, duloxetine and milnacipran in fibromyalgia syndrome: A systematic review with meta-analysis. Rheumatology (Oxford) 2011;50:532-543.
Moldofsky H, Harris HW, Archambault WT, Kwong T, Lederman S. Effects of bedtime very low dose cyclobenzaprine on symptoms and sleep physiology in patients with fibromyalgia syndrome: a double-blind randomized placebo-controlled study. J Rheumatol. 2011;38(12):2653-63
Arnold LM, Hess EV, Hudson JI, et al. A randomized, placebocontrolled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia. Am J Med. 2002;112: 191–7.
Walitt B, Urrutia G, Nishishinya MB, Cantrell SE, Hauser W. Selective serotonin reuptake inhibitors for fibromyalgia syndrome.Cochrane Database of Systematic Reviews 2015;Issue 6. Art. No.: CD011735.
Häuser W, Urrútia G, Tort S, Üçeyler N, Walitt B. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia syndrome. Cochrane Database Syst Rev. 2013;2013(1), CD010292.
Arnold LM, Clauw D, Wang F, et al. Flexible dosed duloxetine in the treatment of fibromyalgia: a randomized, double-blind, placebocontrolled trial. J Rheumatol. 2010;37:2578–86.
Lunn MPT. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev 2014 Jan 3;(1)
Gendreau R M, Thorn M D, Gendreau J F, et al. Efficacy of milnacipran in patients with fibromyalgia. J Rheumatol, 2005; 1975-85.
Derry S, Gill D, Phillips T, Moore RA. Milnacipran for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2012:14.
Ormseth MJ, Eyler A.E, Hammonds CL, Boomershine CS. Milnacipran for the management of fibromyalgia syndrome. J Pain Res. 2010;3:15-24.
Tort S, Urrútia G, Nishishinya MB, Walitt B. Monoamine oxidase inhibitors (MAOIs) for fibromyalgia syndrome. Cochrane Database Syst Rev 2012 Apr18;(4):CD009807.
Hannonen P Malminiemi K, Yli-Kerttula U, et al. A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder. Br J Rheumatol, 1998; 1279-86.
Koyuncu H, Kılınç F, Aydın T, Nejat F, Uludağ M. Fibromiyalji sendromunda moklobemidin klinik etkinlik ve tolerabilitesi. Turkish Journal of Physical Medicine and Rehabilitation 2004;50:3.
Perrot S, Russell I. More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: A meta-analysis examining six core symptoms. Eur J Pain 2014;18:1067-1080.
McQuay H.Carroll D.,Jadad A.R., et al. Anticonvulsant drugs for management of pain: a systematic review. BMJ, 1995;. 1047-52.
Chinn S, Caldwell W, Gritsenko K. Fibromyalgia Pathogenesis and Treatment Options Update. Curr Pain Headache Rep. 2016 Apr;20(4):25.
Crofford LJ, Mease PJ, Simpson SL. Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo controlled trial with pregabalin. Pain. 2008;136:419–31. A promising, long-term placebo-controlled trial demonstrating how pregabalin improves multiple dimensions of fibromyalgia, including pain, sleep, fatigue, and quality of life.
Üçeyler N, Sommer C, Walitt B, Häuser W. Anticonvulsants for fibromyalgia. Cochrane Database Syst Rev. 2013;2013(10), CD010782. doi:10.1002/14651858.CD010782. A meta-analysis of various anticonvulsant agents for use towards fibromyalgia symptoms.
Pauer L, Winkelmann A, Arsenault P, et al. An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia. J Rheumatol 2011;38(12):2643-52.
Cooper TE, Derry S, Wiffen PJ, Moore RA. Gabapentin for fibromyalgia pain in adults. Cochrane Database of Systematic Reviews 2017; Issue 1. Art. No.: CD012188.
Arnold LM, Goldenberg D, Stanford S, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo- controlled, multicenter trial. Arthritis Rheum. 2007;56: 1336–44.
Skrabek RQ, Galimova L, Ethans K, et al. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008;9:164–73.
Ware MA, Fitzcharles MA, Joseph L, et al. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg. 2010;110:604–10.
Farber L.,Stratz T.H.,Bruckle W., et al. Short-term treatment of primary fibromyalgia with the 5-HT3-receptor antagonist tropisetron. Results of a randomized, double-blind, placebo-controlled multicenter trial in 418 patients. Int J Clin Pharmacol Res, 2001; 1-13.
Späth M, Stratz T, Neeck G,etal. Efficacy and tolerability ofintravenous tropisetron in the treatment of fibromyalgia. Scand J Rheumatol. 2004;33:267–27.
Hocking G.,Cousins M.J., Ketamine in chronic pain management: an evidencebased review. Anesth Analg, 2003; 1730-9.
Graven-Nielsen, T.,Aspegren Kendall S.,Henriksson K.G., et al. Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients. Pain, 2000; 483-91.
Holman A.J.,Myers R.R., A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis Rheum, 2005; 2495-505.
Russel IJ, Holman AJ, Swick TJ, et al. S Sodium oxybate reduces pain, fatigue, and sleep disturbance and improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind, placebo-controlled study. Pain. 2011;152:1007–17.
D. Evcik, A. Ketenci, ve D. Sindel, “Fibromiyalji Tanı ve Tedavi Önerileri Kılavuzu 2018”. Available at: http://www.tftr.org.tr/tr/static/dokumanlar.
Bair MJ, Krebs EE. Fibromyalgia. Ann Intern Med. 2020 Mar 3;172(5):ITC33-ITC48.
