Fibromyalgia Treatment Requires Medication Trial and Error

Pharmacy TimesMarch 2020
Volume 88
Issue 3

Many options are available, but no single one is effective for all symptoms of this disorder.

Fibromyalgia is a chronic disorder that manifests as widespread concentration difficulties, fatigue, headaches, mood changes, pain, sleep disruption,1-3 and tenderness.

Patients may also have anxiety, depression, functional impairment of daily activities, and other unexplained symptoms. Emotional distress, endocrine disorders, immune activation, and physical trauma have the potential to trigger fibromyalgia. Women are affected more often than men, and fibromyalgia generally presents in middle-aged or young patients.4,5 Its prevalence in the United States has been estimated at about 2%, but thought leaders indicate that this figure is low.6


Although the exact causes of fibromyalgia are unknown, experts suspect a combination of environmental and genetic factors. Researchers indicate that the condition may emanate from 2 mechanisms that affect the central nervous system (CNS): CNS hyperreactivity and a decreased pain modulation capacity in the CNS, probably associated with decreased activity of serotonergic/noradrenergic pathways.5,7 Patients with fibromyalgia may have lower cerebrospinal fluid levels of noradrenaline metabolites and lower levels of 5-hydroxyindoleacetic acid, serum serotonin, and tryptophan than people who do not have fibromyalgia. They may also have higher levels of nerve growth factor, pronociceptive (pain sensing) neurotransmitters, and substance P. Additionally, patients tend to have functionally impaired and lower-density small nerve fibers.8 Researchers are also looking at other possible causes or contributing factors, such as aberrant sleep architecture, abnormal autonomic nervous system functioning, dysfunctional dopaminergic neurotransmission, catechol-O-methyltransferase gene polymorphisms, and hypothalamic—pituitary–adrenal axis changes. Psychological and physical factors also seem to affect each patient’s fibromyalgia presentation.9

The overall approach to treating fibromyalgia is described in the figure.10,11 A main strategy in treating fibromyalgia is to use interventions to limit peripheral input that increases allodynia, hyperal gesia, and pain. Further, it is important to address sources of comorbid pain.12 The table13 lists the categories of medications used most often, and pharmacists should note that they are typically used in combination. As patients often cannot tolerate recommended doses, the principle of “start low, go slow” needs to be applied.

Many patients with fibromyalgia experience depression. Treating depression will not cure fibromyalgia but it may improve patients’ sleep and reduce pain.14 The FDA has approved 3 drugs specifically for fibromyalgia: the antidepressants duloxetine and milnacipran to relieve fatigue, pain, and sleep problems, and pregabalin to improve sleep and reduce pain.15

Clinicians often employ gabapentin and pregabalin to enhance health-related quality of life, improve sleep, and treat chronic pain. Although the tricyclic antidepressants have fallen out of use for many conditions, amitriptyline has remained a useful adjunct in fibromyalgia, especially in combination with fluoxetine or pregabalin, plus duloxetine.10,11 Low-dose amitriptyline, cyclobenzaprine, and pregabalin, administered at bedtime, are also used to address sleep disturbances.11 Guidelines also recommend tramadol, administered alone or together with acetaminophen, as studies indicate that it reduces pain by 30%.13


Unfortunately, many patients are intolerant of or unresponsive to these drugs, indicating an unmet need for better, targeted medications. Researchers are investigating IMC-1, which is a fixed-dose combination of famciclovir, an antiviral nucleoside analog, and celecoxib, a COX-2 inhibitor with unique antiviral activity. The FDA gave this product a fast track designation based on phase 2 study results.16,17 The theory behind this combination is that herpes viruses seem to upregulate COX-2 enzymes, and many patients with fibromyalgia may be unable to suppress the virus adequately.16 Other agents under study include neurotrophins, mast cell stabilizers, and mirogabalin, a more specific cousin of gabapentin or pregabalin.13

Patients with fibromyalgia often receive potent opioid analgesics from clinicians who are inexperienced in treating this condition. Opioids have limited efficacy in most of these patients and are generally not recommended, except for those with severe allodynia who failed to respond to other approaches. If patients are taking high doses of opioids, clinicians should gradually withdraw opioids under close medical supervision.18


Many patients with fibromyalgia have cognitive limitations and may process verbal information poorly. Providing understandable written instructions describing medications and schedules is the best way to ensure adherence. Clinicians should instruct patients to ask about OTC medications or supplements before using them. Often, patients with this disorder experience symptoms that wane and wax, so identifying and avoiding triggers is important. A key intervention is exercising moderately and pacing one’s activity to match energy levels.19

In addition, as they are likely to take several if not many drugs, patients will need help identifying ways to ensure adherence to medication.


Many options are available to treat fibromyalgia, but no single option is effective for its symptom constellation. Treatment is a balancing act and requires considerable trial and error. A final reminder is important: Avoid anxiolytics, hypnotics, opioids, and skeletal muscle relaxants that have abuse potential or may worsen cognitive dysfunction and fatigue.

Jeanette Y. Wick, RPh, MBA, FASCP, is the assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.


  • Benca RM, Ancoli-Israel S, Moldofsky H. Special considerations in insomnia diagnosis and management: depressed, elderly, and chronic pain populations. J Clin Psychiatry. 2004;65(suppl 8):26-35.
  • Bigatti SM, Hernandez AM, Cronan TA, Rand KL. Sleep disturbances in fibromyalgia syndrome: relationship to pain and depression. Arthritis Rheum. 2008;59(7):961-967. doi: 10.1002/art.23828.
  • Moldofsky H. The significance, assessment, and management of nonrestorative sleep in fibromyalgia syndrome. CNS Spectr. 2008;13(suppl 5):22-26.
  • López-Pousa S, Garre-Olmo J, de Gracia M, Ribot J, Calvó-Perxas L, Vilalta-Franch J. Development of a multidimensional measure of fibromyalgia symptomatology: the comprehensive rating scale for fibromyalgia symptomatology [published online February 4, 2013]. J Psychosom Res. 2013;74(5):384-392. doi: 10.1016/j.jpsychores.2012.12.018.
  • Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol. 2010;23(5):611-615. doi: 10.1097/ACO.0b013e32833c348b.
  • Katz RS, Wolfe F, Michaud K. Fibromyalgia diagnosis: a comparison of clinical, survey, and American College of Rheumatology criteria. Arthritis Rheum. 2006;54(1):169-176.
  • Häuser W, Ablin J, Fitzcharles MA, et al. Fibromyalgia. Nat Rev Dis Primers. 2015;1:15022. doi: 10.1038/nrdp.2015.22.
  • Üçeyler N, Zeller D, Kahn AK, et al. Small fibre pathology in patients with fibromyalgia syndrome [published online March 9, 2013]. Brain. 2013;136(Pt 6):1857-1867. doi: 10.1093/brain/awt053.
  • Staud R. Peripheral pain mechanisms in chronic widespread pain. Best Pract Res Clin Rheumatol. 2011;25(2):155-164. doi: 10.1016/j.berh.2010.01.010.
  • Macfarlane GJ, Kronisch C, Atzeni F, et al. EULAR recommendations for management of fibromyalgia [published online May 5, 2017]. Ann Rheum Dis. 2017;76(12):e54. doi: 10.1136/annrheumdis-2017-211587.
  • Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia [published online July 4, 2016]. Ann Rheum Dis. 2017;76(2):318-328. doi: 10.1136/annrheumdis-2016-209724.
  • Calandre EP, Hidalgo J, Rico-Villademoros F. Use of ziprasidone in patients with fibromyalgia: a case series. Rheumatol Int. 2007;27(5):473-476.
  • Atzeni F, Gerardi MC, Masala IF, Alciati A, Batticciotto A, Sarzi-Puttini P. An update on emerging drugs for fibromyalgia treatment [published online December 19, 2017]. Exp Opin Emerg Drugs. 2017;22(4):357-367. doi: 10.1080/14728214.2017.1418323.
  • Häuser W, Bernardy K, Üçeyler N, Sommer C. Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis. JAMA. 2009;301(2):198-209. doi: 10.1001/jama.2008.944.
  • FDA. Living with fibromyalgia, drugs approved to manage pain. FDA website. Updated January 31, 2014. Accessed February 19, 2020.
  • Pridgen WL, Duffy C, Gendreau JF, Gendreau RM. A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia. J Pain Res. 2017;10:451-460. doi: 10.2147/JPR.S127288.
  • Eslava-Kim L. Combo tx fast tracked for fibromyalgia. MPR. January 29, 2016. Accessed February 19, 2020.
  • Littlejohn GO, Guymer EK, Ngian GS. Is there a role for opioids in the treatment of fibromyalgia [published online June 14, 2016]? Pain Manag. 2016;6(4):347-355. doi: 10.2217/pmt-2016-0012.
  • Goldenberg DL. Multidisciplinary modalities in the treatment of fibromyalgia. J Clin Psychiatry. 2008;69(suppl 2):30-34.

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