Nonarticular Rheumatism/Regional Pain Syndrome Medication

Updated: Aug 24, 2023
  • Author: Evan Dombrosky, MD; Chief Editor: Herbert S Diamond, MD  more...
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Medication Summary

Fibromyalgia and multiple bursitis-tendonitis syndrome

The US Food and Drug Administration (FDA) has approved three drugs for use in fibromyalgia: pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella). [53] Pregabalin is used to reduce pain and improve sleep; it can be given at a dose up to 450 mg/day. [54]  The antidepressants duloxetine and milnacipran, which are used to relieve pain, fatigue, and sleep problems, are generally used at lower doses than for treatment of depression. [55, 56]

Duloxetine was approved by the FDA for fibromyalgia in adolescents aged 13-17 years. In a randomized, placebo-controlled trial, a total of 184 patients with juvenile fibromyalgia received duloxetine (n = 91) or placebo (n = 93), of which 149 patients (81%) completed the 13-week double-blind treatment period. Of those, significantly more patients on duloxetine compared with placebo had a reduction in pain severity of at least 30% to 50%. [57]   

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. [58] The dose can be uptitrated 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. [59] Other less-sedating TCAs (eg, nortriptyline) can be substituted for amitriptyline in the evening if necessary because of sedation.

Gabapentin has been used off-label for fibromyalgia syndrome because of its salutary effects on chronic pain. A clinical trial has shown benefit in fibromyalgia. [60]  

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 up to 10 mg three times a day.

Analgesic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) may be helpful. One controlled trial showed benefits with tramadol (50-400 mg in divided doses) [61] ; 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 small study that evaluated low-dose naltrexone (4.5 mg) as therapy for fibromyalgia found that it reduced symptoms by about 30%, while placebo reduced symptoms by only 2%. [62] Another study showed that sodium oxybate could improve symptoms by about 30% (compared with 10% for placebo). [63] 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.



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.



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.