Nonarticular Rheumatism/Regional Pain Syndrome Medication
- Author: Daniel Muller, MD, PhD; Chief Editor: Herbert S Diamond, MD more...
Medication Summary
Fibromyalgia and multiple bursitis-tendonitis syndrome
Nonrestorative sleep is a significant problem for patients with fibromyalgia. Initial drug therapy consists of a low-dose sedating tricyclic antidepressant (TCA), usually amitriptyline (5-10 mg) 1 hour prior to bedtime.[17] The dose is titrated upward every 5-14 days as tolerated, using the minimal dose to achieve restorative sleep. TCAs can cause excessive sedation; therefore, sertraline 25 mg in the morning or another of the more activating antidepressants (eg, fluoxetine) can be added.[18] Other less-sedating TCAs can be substituted for amitriptyline in the evening (eg, nortriptyline) if necessary because of sedation. Dual-action serotonin and norepinephrine reuptake inhibitors, such as milnacipran and duloxetine, have shown to be helpful in fibromyalgia.[19, 20]
Gabapentin has been used off-label for fibromyalgia syndrome because of its salutary effects on chronic pain. A recent clinical trial has shown benefit in fibromyalgia.[21] Pregabalin, a similar drug, has been shown to be modestly beneficial in patients with fibromyalgia syndrome at a dose of 450 mg/day.[22]
Trazodone can also be particularly helpful for sedation at night and may cause fewer adverse effects than amitriptyline. Doxepin, a non-TCA antidepressant, can be useful in liquid form to titrate at low doses (2-5 mg) for sedation at night. Cyclobenzaprine can relax muscles and can be used as a single dose at night (2.5-10 mg) or, commonly, at 10 mg tid.
Analgesic effects of NSAIDs may be helpful. One controlled trial showed benefits with tramadol (50-400 mg in divided doses)[23] ; however, tramadol used in combination with antidepressants can cause serotonin syndrome and increased sedation. Tramadol may play a role by allowing a 4-week drug holiday from antidepressant therapy to reset neural receptors and, in intermittent therapy, for exacerbations. Avoid long-term use of benzodiazepines and narcotics.
A recent small study evaluated low-dose naltrexone (4.5 mg) as therapy for fibromyalgia. They found that it reduced symptoms by about 30%, while placebo reduced symptoms by only 2%.[24] Another study showed that sodium oxybate could improve symptoms by about 30% (compared with 10% for placebo).[25] However, access to sodium oxybate is restricted in the United States.
Regional and local bursitis and tendonitis
NSAIDs can decrease inflammation. Corticosteroid infiltrations may provide short-term and, occasionally, long-term benefit. The Achilles tendon sheath must not be injected with corticosteroids because of the risk of tendon rupture. Patients with septic bursitis or tendonitis and systemic symptoms should be admitted for intravenous antibiotic therapy.
See Temporomandibular Joint Syndrome, Carpal Tunnel Syndrome, Thoracic Outlet Syndrome, Tendonitis, and Bursitis.
Antidepressants
Class Summary
Some antidepressants provide sedation and relieve chronic pain. They may have a moderate-to-marked sedative effect.
Milnacipran (Savella)
Selective serotonin and norepinephrine reuptake inhibitor (SSNRI). Exact mechanism of central pain inhibitory action and ability to improve symptoms of fibromyalgia unknown. Indicated for fibromyalgia.
Amitriptyline (Elavil)
Analgesic for certain chronic and neuropathic pain.
Sertraline (Zoloft)
SSRI, less sedating than TCAs but appears to improve pain symptoms.
Doxepin (Sinequan)
Inhibits histamine and acetylcholine activity and has proven useful in treatment of various forms of depression associated with chronic and neuropathic pain. Prominent sedative effect. Useful in oral concentrate, 10 mg/mL, to titrate small doses.
Trazodone (Desyrel)
5-HT2–receptor antagonist that inhibits reuptake of 5-HT. Negligible affinity for cholinergic, adrenergic, dopaminergic, or histaminic receptors. Intermediate sedation activity.
Fluoxetine (Prozac)
SSRI, less sedating than TCAs but appears to improve symptoms of pain.
Duloxetine (Cymbalta)
Potent neuronal serotonin inhibitor and norepinephrine reuptake inhibitor. Antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in CNS.
Nonsteroidal anti-inflammatory agents (NSAIDS)
Class Summary
Although most NSAIDs are used primarily for their anti-inflammatory effects, they are effective analgesics and are useful for the relief of mild-to-moderate pain.
Ibuprofen (Ibuprin, Advil, Motrin)
DOC for mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Centrally acting analgesics
Class Summary
Pain control is essential to quality patient care. Analgesics ensure patient comfort and have sedating properties.
Tramadol (Ultram)
Binds to mu opioid receptors and slightly inhibits reuptake of norepinephrine and serotonin.
Muscle relaxants
Class Summary
These agents are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.
Cyclobenzaprine (Flexeril)
Structurally similar to TCAs. Has anticholinergic and sedative adverse effects.
Anticonvulsants
Class Summary
These agents may alleviate chronic pain.
Gabapentin (Neurontin)
Membrane stabilizer, a structural analogue of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Appears to exert action via the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gaited calcium channels. Used to manage pain and provide sedation in neuropathic pain.
Pregabalin (Lyrica)
Structural derivative of GABA. Mechanism of action unknown. Binds with high affinity to alpha2-delta site (a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. Indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, or fibromyalgia. It is also indicated for adjunctive therapy in partial-onset seizures.
Schur EA, Afari N, Furberg H, Olarte M, Goldberg J, Sullivan PF. Feeling bad in more ways than one: comorbidity patterns of medically unexplained and psychiatric conditions. J Gen Intern Med. Jun 2007;22(6):818-21. [Medline].
Abeles AM, Pillinger MH, Solitar BM, Abeles M. Narrative review: the pathophysiology of fibromyalgia. Ann Intern Med. May 15 2007;146(10):726-34. [Medline].
Mountz JM, Bradley LA, Modell JG, et al. Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. Jul 1995;38(7):926-38. [Medline].
Wolfe F, Russell IJ, Vipraio G, et al. Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J Rheumatol. Mar 1997;24(3):555-9. [Medline].
Light AR, White AT, Hughen RW, Light KC. Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain. Oct 2009;10(10):1099-112. [Medline].
Wolfe F, Ross K, Anderson J, et al. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. Jan 1995;38(1):19-28. [Medline].
Wolfe F, Anderson J, Harkness D, et al. Health status and disease severity in fibromyalgia: results of a six-center longitudinal study. Arthritis Rheum. Sep 1997;40(9):1571-9. [Medline].
Wolfe F, Ross K, Anderson J, Russell IJ. Aspects of fibromyalgia in the general population: sex, pain threshold, and fibromyalgia symptoms. J Rheumatol. Jan 1995;22(1):151-6. [Medline].
Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. Feb 1990;33(2):160-72. [Medline].
Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL. Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome. Science. Oct 8 2009;[Medline]. [Full Text].
Häuser W, Bernardy K, Arnold B, Offenbächer M, Schiltenwolf M. Efficacy of multicomponent treatment in fibromyalgia syndrome: a meta-analysis of randomized controlled clinical trials. Arthritis Rheum. Feb 15 2009;61(2):216-24. [Medline].
[Guideline] Carville SF, Arendt-Nielsen S, Bliddal H, Blotman F, Branco JC, Buskila D, et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. Apr 2008;67(4):536-41. [Medline].
Goode AP, Freburger J, Carey T. Prevalence, practice patterns, and evidence for chronic neck pain. Arthritis Care Res (Hoboken). Nov 2010;62(11):1594-601. [Medline]. [Full Text].
Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. Lancet. Nov 20 2010;376(9754):1751-67. [Medline].
Bäcker M, Lüdtke R, Afra D, et al. Effectiveness of leech therapy in chronic lateral epicondylitis: a randomized controlled trial. Clin J Pain. Jun 2011;27(5):442-7. [Medline].
Hoffman JH. Guidelines for Beneficial Group Exercise for Fibromyalgia. Practical Pain Management. 2007/06;7:50-57.
Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. Nov 17 2004;292(19):2388-95. [Medline].
Goldenberg D, Mayskiy M, Mossey C, et al. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum. Nov 1996;39(11):1852-9. [Medline].
Gendreau R, Mease P, Rao S, et al. Milnacipran: A potential new treatment of fibromyalgia. Arthritis Rheum. 2003;48:S616.
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. Sep 2004;50(9):2974-84. [Medline].
Arnold LM, Goldenberg DL, Stanford SB, Lalonde JK, Sandhu HS, Keck PE Jr. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum. Apr 2007;56(4):1336-44. [Medline].
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. Apr 2005;52(4):1264-73. [Medline].
Russell IJ, Kamin M, Bennett RM, Schnitzer TJ, Green JA, Katz WA. Efficacy of Tramadol in Treatment of Pain in Fibromyalgia. J Clin Rheumatol. Oct 2000;6(5):250-7. [Medline].
Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. May-Jun 2009;10(4):663-72. [Medline].
Russell IJ, Perkins AT, Michalek JE,. Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: a randomized, double-blind, placebo-controlled, multicenter clinical trial. Arthritis Rheum. Jan 2009;60(1):299-309. [Medline].
Wigers SH, Stiles TC, Vogel PA. Effects of aerobic exercise versus stress management treatment in fibromyalgia. A 4.5 year prospective study. Scand J Rheumatol. 1996;25(2):77-86. [Medline].
Jentoft ES, Kvalvik AG, Mengshoel AM. Effects of pool-based and land-based aerobic exercise on women with fibromyalgia/chronic widespread muscle pain. Arthritis Rheum. Feb 2001;45(1):42-7. [Medline].
Sheon RP, Moskowitz RW, Goldberg VM. Soft Tissue Rheumatic Pain: Recognition, Management, and Prevention. 3rd ed. Baltimore, Md: Williams and Wilkins; 1996.
Sunshine W, Field TM, Quintino O, Fierro K, Kuhn C, Burman I, et al. Fibromyalgia benefits from massage therapy and transcutaneous electrical stimulation. J Clin Rheumatol. Feb 1996;2(1):18-22. [Medline].
Ferraccioli G, Ghirelli L, Scita F, et al. EMG-biofeedback training in fibromyalgia syndrome. J Rheumatol. Aug 1987;14(4):820-5. [Medline].
Haanen HC, Hoenderdos HT, van Romunde LK, et al. Controlled trial of hypnotherapy in the treatment of refractory fibromyalgia. J Rheumatol. Jan 1991;18(1):72-5. [Medline].
Goldenberg DL, Kaplan KH, Nadeau MG. A controlled study of a stress-reduction, cognitive-behavioral treatment program in fibromyalgia. J Musculoskel Pain. 1994;2:53-66.
Taylor S, Thordarson DS, Maxfield L, et al. Comparative efficacy, speed, and adverse effects of three PTSD treatments: exposure therapy, EMDR, and relaxation training. J Consult Clin Psychol. Apr 2003;71(2):330-8. [Medline].
Cohen H, Neumann L, Haiman Y, et al. Prevalence of post-traumatic stress disorder in fibromyalgia patients: overlapping syndromes or post-traumatic fibromyalgia syndrome?. Semin Arthritis Rheum. Aug 2002;32(1):38-50. [Medline].
Kaplan KH, Goldenberg DL, Galvin-Nadeau M. The impact of a meditation-based stress reduction program on fibromyalgia. Gen Hosp Psychiatry. Sep 1993;15(5):284-9. [Medline].
Kabat-Zinn J. Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness. New York: Dell Publishing; 1990.
Deluze C, Bosia L, Zirbs A, et al. Electroacupuncture in fibromyalgia: results of a controlled trial. BMJ. Nov 21 1992;305(6864):1249-52. [Medline].
Assefi NP, Sherman KJ, Jacobsen C, et al. A randomized clinical trial of acupuncture compared with sham acupuncture in fibromyalgia. Ann Intern Med. Jul 5 2005;143(1):10-9. [Medline].
Bell IR, Lewis DA, Brooks AJ, et al. Improved clinical status in fibromyalgia patients treated with individualized homeopathic remedies versus placebo. Rheumatology (Oxford). May 2004;43(5):577-82. [Medline].
Fisher P, Greenwood A, Huskisson EC, et al. Effect of homeopathic treatment on fibrositis (primary fibromyalgia). BMJ. Aug 5 1989;299(6695):365-6. [Medline].
Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol. May 1995;22(5):953-8. [Medline].
Rossini M, Di Munno O, Valentini G, Bianchi G, Biasi G, Cacace E. Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp Rheumatol. Mar-Apr 2007;25(2):182-8. [Medline].
Muller D, Selfridge N. Fibromyalgia syndrome. In: Rakel D, ed. Integrative Medicine. 2nd ed. Philadelphia, PA: Saunders; 2007:509-18.
Turk DC, Okifuji A, Sinclair JD, Starz TW. Pain, disability, and physical functioning in subgroups of patients with fibromyalgia. J Rheumatol. Jul 1996;23(7):1255-62. [Medline].
Schleicher H, Alonso C, Shirtcliff EA, Muller D, Loevinger BL, Coe CL. In the face of pain: the relationship between psychological well-being and disability in women with fibromyalgia. Psychother Psychosom. 2005;74(4):231-9. [Medline].

