Cymbalta (duloxetine hydrochloride) is a selective serotonin and norepinephrine reuptake inhibitor (SNRI). It is a prescription-only drug approved for the treatment of chronic musculoskeletal pain and chronic low back pain, which can be caused by conditions such as osteoarthritis. Cymbalta was first approved by the U.S. Food and Drug Administration (FDA) in 2004 for major depressive disorder. Subsequently, it was also approved for treatment of anxiety, pain caused by diabetic neuropathy, and pain caused by fibromyalgia before gaining FDA approval for chronic musculoskeletal pain in 2010.

Cymbalta increases the action of serotonin and norepinephrine, which are natural neurotransmitters produced by the body. This effect of Cymbalta alleviates depression and anxiety and decrease pain signals in the brain, spinal cord, and nerves.1 It has also been suggested that Cymbalta could reduce inflammation or oxidative damage, but these theories have not been proven at this time.

Prior to the approval of Cymbalta for musculoskeletal pain, several double-blind, placebo-controlled, randomized clinical trials confirmed that study participants taking Cymbalta had significantly greater pain reduction than participants taking a placebo.2

Since its approval, more recent studies have shown that Cymbalta reduces chronic musculoskeletal pain, including that from osteoarthritis. However, it does have three to four times more reported gastrointestinal side effects than placebo.3

Like any medication, Cymbalta has potential side effects and other considerations that you must weigh before deciding to take it.

Common side effects include:4

• Nausea
• Dry mouth
• Constipation
• Sleepiness
• Sweating
• Decreased appetite

Though less common, Cymbalta may also cause:

• Vomiting
• Diarrhea
• Stomach pain
• Urinary retention
• Dizziness
• Headaches
• Tiredness
• Muscle pain
• Muscle cramps
• Diminished sexual functioning
• Shaking

Serious side effects are not common, but they can have major consequences. The most serious side effects associated with Cymbalta include:2

• Bleeding: This is more likely if you have a bleeding disorder or if you are taking a blood thinner.
• Seizures: Cymbalta may lower seizure threshold, causing increased seizures in people with epilepsy.
• Mania: Because of its antidepressant effect, Cymbalta may cause a hyperactive and unfocused state of mind.
• Low blood pressure: A warning was added to Cymbalta in 2014 for orthostatic hypotension, falls, and syncope (fainting).
• Serotonin syndrome—a life-threatening condition that causes symptoms of anxiety, high blood pressure, rapid heartbeat, rapid breathing, sweating, and tremors
• Suicidal thoughts and behaviors: Cymbalta had a black box warning related to this concern added in 2014.

Cymbalta is not recommended for women who are pregnant, for breastfeeding mothers, or for people who have glaucoma or kidney or liver disease.4

If you have a predisposition to or a history of suicidal thoughts, drug abuse, bleeding, or seizures, Cymbalta can exacerbate these conditions.

Certain medications may increase or decrease the effect of Cymbalta, or cause worse or different side effects. Several categories of medications have been proven to interact with Cymbalta, while there are sporadic case reports that others interact as well, without compelling evidence.

Cymbalta has been proven to interact with the following:2

• Alcohol, which, in combination with Cymbalta, can cause severe liver injury
• Quinolones, such as ciprofloxacin and fluoroquinolone
• Antidepressants, including nortriptyline, amitriptyline, and imipramine
• Antipsychotic medications, especially thioridazine
• Antiarrhythmics, including propafenone and flecainide
• Narcotic pain medications, such as codeine and oxycodone
• Blood thinners, such as warfarin, heparin, rivaroxaban, and aspirin
• All sleep medications and tranquilizers, because they are known to have an additive effect resulting in excessive drowsiness

Cymbalta comes as a delayed-release capsule in 20, 30, and 60 mg strengths. It is usually recommended that you start with an initial dose of 30 mg per day and increase to the target dose (60 mg daily) within a week. Take your prescription according to directions on the label.

Be sure to swallow the capsule whole without crushing, splitting, chewing, or opening it.4 You can take Cymbalta with or without food, but eating something can help prevent stomach upset.

While Cymbalta is an approved treatment for chronic musculoskeletal pain, not everyone tolerates the medication or experiences the same degree of pain relief from it; some do not experience pain relief at all. Remember that your experience may differ from someone else's, both in terms of how well the medication works for you and what side effects you experience. Monitor your pain and alert your doctor to any concerns promptly.