Milnacipran for the Treatment of Fibromyalgia
Purpose of review
This is a comprehensive review of the literature regarding the use of milnacipran in treating fibromyalgia. A chronic pain disorder with other system disturbances, fibromyalgia is often resistant to many therapeutic approaches. This review presents the background, evidence, and indications for using milnacipran as a treatment option for this condition.
Recent Findings
The definition of fibromyalgia has evolved over many years as it is a relatively tricky syndrome to measure objectively. Today, it is characterized by chronic, widespread pain accompanied by alterations in sleep, mood, and other behavioral aspects. A variety of therapeutic regimens currently used to treat the syndrome as a singular approach are rarely effective.
Milnacipran is one of three drugs currently approved by the FDA for the treatment of fibromyalgia. It acts as a serotonin and norepinephrine reuptake inhibitor, which results in decreased pain transmission. Milnacipran remains an effective treatment option for fibromyalgia in adults and needs to be further evaluated with existing therapeutic approaches.
Summary
Fibromyalgia is a broad-spectrum disorder primarily characterized by chronic pain coupled with disturbances in cognitive functioning and sleep. The progression of this syndrome is often debilitating and significantly affects the quality of life. Milnacipran is one of three FDA-approved drugs used to alleviate the symptom burden and is comparatively more therapeutic in specific domains of fibromyalgia. A more holistic approach is needed to treat fibromyalgia effectively and further research, including direct comparison studies, should be conducted to fully evaluate the usefulness of this drug.
1. Perrot S. Fibromyalgia: A misconnection in a multiconnected world? Eur J Pain. 2019;23(5):866-873. doi:10.1002/ejp.1367
2. Arnold LM, Bennett RM, Crofford LJ, et al. AAPT Diagnostic Criteria for Fibromyalgia. J Pain. 2019;20(6):611-628. doi:10.1016/j.jpain.2018.10.008
3. Galvez-Sánchez CM, Duschek S, Del Paso GAR. Psychological impact of fibromyalgia: Current perspectives. Psychol Res Behav Manag. 2019;12:117-127. doi:10.2147/PRBM.S178240
4. Borchers AT, Gershwin ME. Fibromyalgia: A Critical and Comprehensive Review. Clin Rev Allergy Immunol. 2015;49(2):100-151. doi:10.1007/s12016-015-8509-4
5. Uçeyler N, Häuser W, Sommer C. A systematic review on the effectiveness of treatment with antidepressants in fibromyalgia syndrome. Arthritis Rheum. 2008;59(9):1279-1298. doi:10.1002/art.24000
6. Clauw DJ. Fibromyalgia: A clinical review. JAMA - J Am Med Assoc. 2014;311(15):1547-1555. doi:10.1001/jama.2014.3266
7. Cabo-Meseguer A, Cerdá-Olmedo G, Trillo-Mata JL. Fibromyalgia: Prevalence, epidemiologic profiles and economic costs. Med Clin (Barc). 2017;149(10):441-448. doi:10.1016/j.medcli.2017.06.008
8. Queiroz LP. Worldwide epidemiology of fibromyalgia topical collection on fibromyalgia. Curr Pain Headache Rep. 2013;17(8). doi:10.1007/s11916-013-0356-5
9. Verbunt JA, Pernot DHFM, Smeets RJEM. Disability and quality of life in patients with fibromyalgia. Health Qual Life Outcomes. 2008;6:8. doi:10.1186/1477-7525-6-8
10. Creed F. A review of the incidence and risk factors for fibromyalgia and chronic widespread pain in population-based studies. Pain. 2020;161(6):1169-1176. doi:10.1097/j.pain.0000000000001819
11. Imbierowicz K, Egle UT. Childhood adversities in patients with fibromyalgia and somatoform pain disorder. Eur J Pain. 2003;7(2):113-119. doi:10.1016/S1090-3801(02)00072-1
12. Bradley LA. Pathophysiology of Fibromyalgia. Am J Med. 2009;122(12 SUPPL.). doi:10.1016/j.amjmed.2009.09.008
13. Tzadok R, Ablin JN. Current and Emerging Pharmacotherapy for Fibromyalgia. Pain Res Manag. 2020;2020. doi:10.1155/2020/6541798
14. Chinn S, Caldwell W, Gritsenko K. Fibromyalgia Pathogenesis and Treatment Options Update. Curr Pain Headache Rep. 2016;20(4):25. doi:10.1007/s11916-016-0556-x
15. Häuser W, Bernardy K, Uçeyler N, Sommer C. Treatment of fibromyalgia syndrome with gabapentin and pregabalin--a meta-analysis of randomized controlled trials. Pain. 2009;145(1-2):69-81. doi:10.1016/j.pain.2009.05.014
16. 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). doi:10.1002/14651858.CD010292
17. Julien N, Goffaux P, Arsenault P, Marchand S. Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain. 2005;114(1-2):295-302. doi:10.1016/j.pain.2004.12.032
18. Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 2009;10(4):663-672. doi:10.1111/j.1526-4637.2009.00613.x
19. Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013;65(2):529-538. doi:10.1002/art.37734
20. Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318-328. doi:10.1136/annrheumdis-2016-209724
21. Baron EP. Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been …. Headache. 2015;55(6):885-916. doi:10.1111/head.12570
22. Distler O, Eich W, Dokoupilova E, et al. Evaluation of the efficacy and safety of terguride in patients with fibromyalgia syndrome: results of a twelve-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2010;62(1):291-300. doi:10.1002/art.25062
23. Sommer C, Häuser W, Alten R, et al. [Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline]. Schmerz. 2012;26(3):297-310. doi:10.1007/s00482-012-1172-2
24. Calandre EP, Rico-Villademoros F, Slim M. An update on pharmacotherapy for the treatment of fibromyalgia. Expert Opin Pharmacother. 2015;16(9):1347-1368. doi:10.1517/14656566.2015.1047343
25. Häuser W, Urrútia G, Tort S, Üçeyler N, Walitt B. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia syndrome. Cochrane Database Syst Rev. 2013;(1). doi:10.1002/14651858.CD010292
26. Pharmaceuticals A, Limited I. Savella - Highlights of prescribing information. 2016;4(4):1-36. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022256s022lbl.pdf
27. Mochizuki D, Hokonohara T, Kawasaki K, Miki N. Repeated administration of milnacipran induces rapid desensitization of somatodendritic 5-HT1A autoreceptors but not postsynaptic 5-HT1A receptors. J Psychopharmacol. 2002;16(3):253-260. doi:10.1177/026988110201600311
28. Pae CU, Marks DM, Shah M, et al. Milnacipran: beyond a role of antidepressant. Clin Neuropharmacol. 2009;32(6):355-363. doi:10.1097/WNF.0b013e3181ac155b
29. Maj J, Rogóz Z, Dlaboga D, Dziedzicka-Wasylewska M. Pharmacological effects of milnacipran, a new antidepressant, given repeatedly on the alpha1-adrenergic and serotonergic 5-HT2A systems. J Neural Transm. 2000;107(11):1345-1359. doi:10.1007/s007020070022
30. Mongeau R, Weiss M, de Montigny C, Blier P. Effect of acute, short- and long-term milnacipran administration on rat locus coeruleus noradrenergic and dorsal raphe serotonergic neurons. Neuropharmacology. 1998;37(7):905-918. doi:10.1016/s0028-3908(98)00083-5
31. Puozzo C, Panconi E, Deprez D. Pharmacology and pharmacokinetics of milnacipran. Int Clin Psychopharmacol. 2002;17 Suppl 1:S25-35. doi:10.1097/00004850-200206001-00004
32. Puozzo C, Leonard BE. Pharmacokinetics of milnacipran in comparison with other antidepressants. Int Clin Psychopharmacol. 1996;11 Suppl 4:15-27. doi:10.1097/00004850-199609004-00003
33. Puozzo C, Pozet N, Deprez D, Baille P, Ung HL, Zech P. Pharmacokinetics of milnacipran in renal impairment. Eur J Drug Metab Pharmacokinet. 1998;23(2):280-286. doi:10.1007/BF03189352
34. Puozzo C, Lens S, Reh C, et al. Lack of interaction of milnacipran with the cytochrome p450 isoenzymes frequently involved in the metabolism of antidepressants. Clin Psychopharmacol. 2005;44(9):977-988. doi:10.2165/00003088-20054409-00007
35. Arnold LM, Palmer RH, Ma Y. A 3-Year, Open-Label, Flexible-Dosing Study of Milnacipran for the Treatment of Fibromyalgia. Clin J Pain. 2013;29(12):1021-1028. doi:10.1097/AJP.0b013e31828440ab
36. Trugman JM, Palmer RH, Ma Y. Milnacipran effects on 24-hour ambulatory blood pressure and heart rate in fibromyalgia patients: A randomized, placebo-controlled, dose-escalation study. Curr Med Res Opin. 2014;30(4):589-597. doi:10.1185/03007995.2013.861812
37. Behlke LM, Lenze EJ, Carney RM. The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases. CNS Drugs. 2020;34(11):1133-1147. doi:10.1007/s40263-020-00763-z
38. Periclou A, Palmer RH, Zheng H, Lindamood C. Effects of milnacipran on cardiac repolarization in healthy participants. J Clin Pharmacol. 2010;50(4):422-433. doi:10.1177/0091270009346059
39. Mease PJ, Clauw DJ, Gendreau RM, et al. The efficacy and safety of milnacipran for treatment of fibromyalgia. A randomized, double-blind, placebo-controlled trial. J Rheumatol. 2009;36(2):398-409. doi:10.3899/jrheum.080734
40. Abtroun L, Bunouf P, Gendreau RM, Vitton O. Is the efficacy of milnacipran in fibromyalgia predictable? A data-mining analysis of baseline and outcome variables. Clin J Pain. 2016;32(5):435-440. doi:10.1097/AJP.0000000000000284
41. Häuser W, Petzke F, Üeyler N, Sommer C. Comparative efficacy and acceptability of amitriptyline, duloxetine and milnacipran in fibromyalgia syndrome: A systematic review with meta-analysis. Rheumatology. 2011;50(3):532-543. doi:10.1093/rheumatology/keq354
42. Häuser W, Petzke F, Sommer C. Comparative Efficacy and Harms of Duloxetine, Milnacipran, and Pregabalin in Fibromyalgia Syndrome. J Pain. 2010;11(6):505-521. doi:10.1016/j.jpain.2010.01.002
43. Arnold LM, Michael Gendreau R, Palmer RH, Gendreau JF, Wang Y. Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: Results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62(9):2745-2756. doi:10.1002/art.27559