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Duloxetine is a fairly new drug released within the last ten years with a proposed mechanism of pharmaceutical activity based on the potentiation of the serotonin and norepinephrine receptors of the central nervous system. It is a very potent inhibitor of the reuptake of serotonin and norepinephrine with some effect also to potential dopamine. The drug also has affinity for adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors, which accounts for its spectrum of pharmacologic activity for treatment of neurologic pain, musculoskeletal pain, depression and anxiety without the significant side effects of the MAOI type antidepressants/antipsychotic. Although the drug has several indications including major depressive disorders (MDD) and generalized anxiety disorder (GAD), for purposes of this article, the focus will be on its indications as an analgesic for fibromyalgia, diabetic peripheral neuropathy(DPN) and chronic musculoskeletal pain.


Duloxetine was found to significantly reduce the pain of distal (pain in the extremities-arms, finger, feet, toes) diabetic peripheral neuropathy (DPN) - the pain experienced by either insulin dependent (IDDM, diabetes type 1) or non-insulin dependent (NIDDM, diabetes type2) with or without acetaminophen in doses of 60mg once or twice daily. These patients had an established diagnosis of DPN for a minimum of six months without relief and found the reduction in symptoms in a 3month time frame.

Fibromyalgia (FM) patients with confirmed diagnosis by meeting the 11 or more of the 18 specific tender pain point’s criteria as determined by the American College of Rheumatology for a minimum of 3 months, noted a relief of at least 50% in .six months.

Duloxetine is indicated in patients with chronic low back skeletal muscle pain and chronic osteoarthritis pain. With a significant relief in symptoms in a 4 month period.


The drug should be avoided in pregnant or lactating women and those with a history of alcoholism due to its severe liver disease warming in those patients of heavy alcohol consumption, though the drug does not enhance the slowing of motor skills which are caused by alcohol. It doesn’t impair judgment, thinking, or memory; the patient however should be warned about operating machines or automobiles until the individual effect is realized. Initially the drug may cause orthostatic hypotension- a sudden drop in blood pressure a patient can experience from sitting to a standing position especially when taken with some blood pressure medications which may also have the same effect initially. The drug should not be taken with MAOI (monoamine oxidase inhibitors-types of other anti-anxiety medications) or those patients diagnosed as having uncontrolled narrow-angle glaucoma (a disease with increased fluid pressure within the eye) The medication should also be avoided in patients with hepatic (liver) insufficiency, renal (kidney) impairment and used in caution in the elderly, though doses need not be adjusted.

Common adverse/side effects include those of the gastrointestinal tract-nausea, vomiting, dry mouth diarrhea or constipation, abdominal pain and dyspepsia. The patient may experience fatigue, flu- like symptoms, headaches, dizziness, insomnia, agitation, cough, sweating and flushing of the face.

More serious effects may be bleeding, seizures, urinary retention, lowered blood levels of sodium (hyponatremia), and potential of various psychiatric conditions.

The drug is enteric coated (a coating that allows dissolution in the intestine) and so the capsule should not be opened, nor chewed /crushed as the coating will be effected and so the absorption into the blood stream.


The dosage for Duloxetine for diabetic peripheral neuropathy is 60mg to start, followed by 60mg daily. Dose for fibromyalgia and chronic muscular-skeletal pain is 30mg to start then 60mg daily. It is available in 20mg, 30mg, and 60mg capsules (The other doses being used for the other indications of MDD-major depressive syndrome and GAD-general anxiety disorder)

DULOXETINE (CYMBALTA) Eli Lilly & Company, Product Literature, 2011
MPR, Monthly Prescribing Reference, Pain Management Edition 2011


My personal experiences with Duloxetine are limited. As outlined in prior articles, my initial treatment regimen is vitamin/nutritional supplementation (over the counter or prescription) and the topicals, then to Lyrica. This is due to the scope of my practice, although Duloxetine (Cymbalta) would be an excellent drug of choice, my patients due to their own self education of medication, think primarily of the drug for depression or anxiety, and I have found compliance a factor. I also have a podiatry practice with an Internal Medicine group, and their feedback regarding the drug for their patients, who may have their own established podiatrist, is very favorable, both for neuropathy and the other indications.

See our other pain medication discussions.