Pharmacologic Therapy for Fibromyalgia

Larry Culpepper, MD, MPH

Department of Family Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts


Patients with fibromyalgia have a wide range of severity of symptoms and disability. Nonpharmacologic therapies provide a framework in which clinicians can help patients adapt to the chronic nature of fibromyalgia, and pharmacologic therapy can provide important additional symptom relief and improvement in functioning.1–3 Such pharmacologic therapy must be individualized based on a comprehensive initial evaluation of the patient with subsequent treatment modifications guided by assessment of the evolution of the disease and the patient’s response to treatment.4–6 Patient symptoms and impairments related to each of the dimensions of the “fibromyalgia triad” (pain, sleep dysfunction, and mood disorders) as well as any other comorbidities, past experiences with treatment, and patient preferences should guide therapy selection.7 The major pharmacologic categories helpful in treating fibromyalgia include anticonvulsants, antidepressants, and hypnotics (AV 1).8

FDA-Approved Treatments

Three medications are approved by the FDA for fibromyalgia—the anticonvulsant pregabalin and the antidepressants duloxetine and milnacipran. All 3 of these agents improve pain symptoms. About 30% of patients taking any one of these can expect to achieve about a 50% or greater symptom reduction, with 50% of patients achieving at least 30% improvement.9,10 Pregabalin improves pain and may be of particular value for patients with significant sleep dysfunction,11 and duloxetine may be especially helpful in those with associated depressive and anxiety symptoms or disorders.12

Other Pharmacologic Options

Other medications may also be useful in treating fibromyalgia. For example, tramadol is often prescribed for pain control in patients with fibromyalgia, and acetaminophen may be synergistic with it, although NSAIDs are generally ineffective, as are opiods.4,13 Antidepressant medications that may be of use include the SNRI desvenlafaxine, the SSRIs, and bupropion. The older TCAs amitriptyline and doxepin, even in low doses, may help with insomnia and pain. The anticonvulsant gabapentin is also an option. For patients with residual sleep dysfunction, zolpidem and eszopiclone may be helpful. In patients with significant anxiety, an intermediate- or long-acting anxiolytic in the evening may be of benefit. In some patients with severe sleep dysfunction at initial presentation, early use of sleep-inducing medication is reasonable.2–7,9

Selecting Medications

AV 2. The Treatment Triangle of Fibromyalgia (01:22)

Medication should be selected based on the patient’s predominant symptoms (AV 2). Most patients will require polypharmacy with 2 or more medications.1,3,6 Since most medication benefit emerges over time, it is reasonable to start with an FDA-approved medication, either singly or in combination with tramadol or a sleep medication. Fibromyalgia patients may be sensitive to side effects, which should be monitored as medications are titrated up to therapeutic doses. Often, patients are fearful of medications based on prior experience; for these patients, the clinician can use medication-specific education, with the general message that the medication is a tool that can help the patient reassert control over his or her life.


AV 3. Managing and Monitoring the Patient With Fibromyalgia (01:38)

Symptom measurement tools can be helpful in allowing patients and physicians to monitor disease status, inform decisions about medication adjustment, and recognize changes due to therapy. Pain scales, depression scales (eg, PHQ-9), and insomnia and fatigue severity indexes may be of value depending on the symptoms that the patient experiences.14 In addition, having the patient keep a diary of activity, exercise, sleep, and other related factors may help clinicians evaluate treatment response as well as treatment adherence. As patients start taking medications, it is important for the clinician to emphasize continued engagement with nonpharmacologic management, including exercise, sleep hygiene, and psychological care.1–3

AV 4. Long-Term Outcomes in Fibromyalgia (00:38)

Fibromyalgia is a chronic condition, so physicians should expect to need to monitor patients over the long term (AV 3). If a patient responds to treatment somewhat, but not fully, the physician should continue to evaluate the patient and adjust his or her treatment regimen accordingly. As symptom response levels off, the patient and physician can address function and long-term goals (AV 4).

For Clinical Use

  • Individualize pharmacologic therapy based on a comprehensive evaluation of the patient with subsequent treatment modifications based on the evolution of the disease and the patient’s response to treatment
  • As patients start taking medications, emphasize continued engagement with nonpharmacologic management, including exercise, sleep hygiene, and psychological care

Drug Names

bupropion (Aplenzin, Wellbutrin, and others), desvenlafaxine (Pristiq), doxepin (Zonalon and others), duloxetine (Cymbalta), eszopiclone (Lunesta), gabapentin (Neurontin and others), milnacipran (Savella), pregabalin (Lyrica), tramadol (Ryzolt, Ultram, and others), zolpidem (Ambien, Zolpimist, and others)


FDA=Food and Drug Administration, NSAID=nonsteroidal anti-inflammatory drug, PHQ=Patient Health Questionnaire, SNRI=serotonin-norepinephrine reuptake inhibitor, SSRI=selective serotonin reuptake inhibitor, TCA=tricyclic antidepressant


All videos are derived from the Webcast “Debates and Directions in Fibromyalgia: Recognizing Signs and Selecting the Appropriate Paths, Part 2,” held in March 2010 by the University of North Texas Health Science Center and featuring Larry Culpepper, MD, MPH, Boston University Medical Center, and Raymond Pertusi, DO, Harvard Vanguard Medical Associates. © 2010 University of North Texas Health Science Center, Fort Worth.

  1. Arnold LM, Bradley LA, Clauw DJ, et al. Multidisciplinary care and stepwise treatment for fibromyalgia. J Clin Psychiatry. 2009;69(12):e35
  2. Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA 2004; 292(19):2388–2395.
  3. Chakrabarty S, Zoorob R. Fibromyalgia. Am Fam Physician. 2007;76(2):247–254.
  4. Buckhardt CS, Goldenberg D, Crofford L, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children. Clinical Practice Guideline, No 4. Glenview, IL: American Pain Society (APS); 2005. Accessed March 7, 2010.
  5. Carville SF, Arendt-Nielsen S, Bliddal H, et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008;67(4):536–541.
  6. Abeles M, Solitar BM, Pillinger MH, et al. Update on fibromyalgia therapy. Am J Med. 2008;121(7):555–561.
  7. Boomershine CS, Crofford LJ. A symptom-based approach to pharmacologic management of fibromyalgia. Nat Rev Rheumatol. 2009;5(4):191–199.
  8. Clauw DJ. Pharmacotherapy for patients with fibromyalgia. J Clin Psychiatry. 2008;69(suppl 2):25–29.
  9. Fitzcharles MA, Costa DD, Poyhia R. A study of standard care in fibromyalgia syndrome: a favorable outcome. J Rheumatol. 2003;30(1):154–159.
  10. Granges G, Zilko P, Littlejohn GO. Fibromyalgia syndrome: assessment of the severity of the condition 2 years after diagnosis. J Rheumatol. 1994;21(3):523-529.
  11. Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52(4):1264–1273.
  12. Arnold LM, Lu Y, Crofford LJ, et al. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum. 2004;50(9):2974–2984.
  13. Bennett RM, Kamin M, Karim R, et al. Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Am J Med. 2003;114(7):537–545.
  14. Lowe B, Kroenke K, Herzog W, et al. Measuring depression outcome with a brief self-report instrument: sensitivity to change of the Patient Health Questionnaire (PHQ-9). J Affect Disord. 2004;81(1):61–66.