Cymbalta® is a type of drug known as a selective SNRI (Serotonin and norepinephrine reuptake inhibitor) and was approved by the FDA for treatment of chronic musculoskeletal pain including osteoarthritis (OA) in 2010. It was first approved by the FDA in 2010 as a treatment for depression, and is also used for other health concerns, including other mood disorders, nerve pain and fibromyalgia.
Cymbalta works by acting on pain inhibitory pathways in the brain. Specifically, it increases natural substances in the brain, serotonin and norepinephrine, which are believed to upregulate the pain inhibitory pathway that stops pain signals reaching the brain. The two clinical studies that led to its approval for OA showed that Cymbalta is about as effective as an NSAID for OA pain relief, without the side effect of potential gastrointestinal bleeding sometimes seen with NSAIDs. However, more than 16 percent of the subjects in these studies stopped taking duloxetine due to an adverse reaction. The three most common seen in the studies were nausea, fatigue and constipation.
American College of Rheumatology Recommendations
The approved dose for chronic musculoskeletal pain is a 60mg capsule taken once a day, swallowed whole; it does not have to be timed with meals but doing so may help alleviate nausea, which can be a side effect with this medicine.
For patients with OA of the hand, knee or hip, ACR has no recommendations regarding the use of duloxetine due to the lack of data from randomized clinical trials at the time of publication.
Possible Side Effects of Cymbalta
The safety of duloxetine has been well established in clinical trials in more than 32,000 patients across all indications. Since its first approval in 2004, over 53 million patients have been treated worldwide. Cymbalta has been shown to be generally safe and well tolerated with no new safety concerns identified in people with OA. The most common side effects are nausea, constipation, dry mouth, diarrhea, fatigue, dizziness, somnolence and insomnia.
More serious side effects have occurred in less than one percent of people taking the drug. If you experience any of these more severe side effects, seek immediate medical attention:
· Liver damage
· Swelling in the face
· Suicidal thoughts and behavior
· Depressed mood or other psychological changes (anxiety, panic attacks, agitation, aggressive behavior or irritability)
· Changes to urinary or sexual habits
· Muscle pain or cramps
In 2014, the FDA added a black box warning to the label of duloxetine. This is the strictest warning put in the labeling of prescription drugs by the FDA when there is reasonable evidence of a serious hazard with the drug. The warning for duloxetine reads as follows:
"WARNING: SUICIDAL THOUGHTS AND BEHAVIORS”
• Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking
• Monitor for worsening and emergence of suicidal thoughts and behaviors."
Keep in mind that this warning is based on studies of people taking duloxetine for major depressive disorder and other psychiatric disorders, not OA.However, your mental health may change in unexpected ways when you take duloxetine or other antidepressants even if you are an adult over 24 years of age, and even if you do not have a mental illness and are not taking it for depression. A warning was also added in 2014 for orthostatic hypotension, falls and fainting. (This is when your blood pressure drops when you stand up from lying or sitting.) The risk of falls is greater if you are taking a drug for high blood pressure in addition to duloxetine. If you are already at risk of falls from age or other conditions, this may be worse with duloxetine, especially when you first start taking it.
Monitor for Side Effects
Let your doctor know if you have unpleasant or worrisome side effects like nausea, vomiting, fainting, dizziness or changes in your mood (see complete list above). Your doctor may be able to lower your dose or suggest another medicine for your pain. Don’t try to treat severe side effects on your own. Though rare, some people are allergic to duloxetine. Call your doctor immediately if you notice any signs of an allergic reaction including difficulty breathing or swallowing, hives, severe itching or swelling of the throat, face, lips or tongue.
Your doctor will want to monitor you and see you often, especially at the beginning of your treatment with duloxetine, to make sure you are not experiencing serious side effects, particularly changes in your mood. Liver damage is not likely if you take duloxetine at the recommended dose. However, liver damage can occur. If your doctor suspects liver damage, she can order blood tests that check the health of your liver.
What can I do to help prevent or ease side effects?
· Stay alert for any signs of agitation, irritability, unusual changes in behavior, and thoughts of suicide or harming yourself.
· To help avoid or reduce nausea, start at the lowest dose (30mg) or take it with food.
· Tell your doctor if you are allergic to duloxetine, or if you take thioridazine or a MAO inhibitor, as these drugs may negatively interact with duloxetine. Other drugs taken with duloxetine may increase or decrease its effectiveness. These include (this is not an exhaustive list):
o antipsychotic medications
o opioid pain medications
o sleep medications
· Give your doctor a list of all medications and vitamins you take, especially products containing St. John's wort or tryptophan, as these may interact with duloxetine. Discuss any other medical conditions you have as well as habits such as alcohol use.
· Take your prescription exactly as instructed by the directions on the label.
· Do not suddenly stop taking duloxetine without talking to your doctor first. Sudden discontinuation can cause adverse side effects, such as nausea; vomiting; diarrhea; anxiety; dizziness; tiredness; headache; pain, burning, numbness, or tingling in the hands or feet; irritability; difficulty falling asleep or staying asleep; sweating; and nightmares. Your doctor will probably want to decrease your dose gradually over time.
· Don’t drive or operate machinery until you know how this medicine affects you.
· If you are pregnant, especially if you are in the last few months of your pregnancy, if you plan to become pregnant or are breast-feeding, or become pregnant while taking duloxetine, tell your doctor. Duloxetine may cause problems in newborns following delivery if it is taken during the last months of pregnancy.
By David Borenstein MD, past president American College Rheumatology & CH Weaver MD Medical Editor