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Fibromyalgia Basics

Duloxetine for Pain
Navigating the Side Effects

Duloxetine (Cymbalta) treats depression and generalized anxiety disorder, but it is supposed to relieve the pain associated with fibromyalgia independent of mental health. It was approved by the Food and Drug Administration (FDA) for fibromyalgia in 2008.

How does duloxetine work? It’s thought to relieve pain by increasing the availability of serotonin and norepinephrine (NE) in the central nervous system. These two chemical transmitters used by your neurons help filter out pain signals in the spinal cord. This reduces the number of signals entering the brain, where they are interpreted as “ouch!” In addition, research indicates that both serotonin and NE are in short supply in the nervous system of people with fibromyalgia, so taking duloxetine makes sense.

Duloxetine is in a drug class called a selective serotonin NE reuptake inhibitor or SNRI. When serotonin and NE are released at the nerve endings, SNRI drugs latch onto these two transmitters and carry them back across the nerve junction. This allows both chemicals to be reused to fight pain. In a way, SNRIs “recycle” the two transmitters that are low in most fibromyalgia patients.

What are the Odds?

In theory, duloxetine sounds like it is a reasonable drug to try for your fibromyalgia, but what are the odds that it helps? Also, how long do you have to take the drug before you notice any benefits, and is there a set dose that works best for most patients with fibromyalgia?

Based on the trials for the FDA-approval using patients with mild symptoms (because they had to go off all of their medications), about 15-20 percent noticed improvements. But for the typical fibromyalgia patient with more moderate symptoms and other painful conditions (not just fibro), duloxetine works in one out of ten patients.1 In fact, this is the same odds of having treatment success with any of the FDA-approved drugs for fibromyalgia.

What about a target dose that you should try before you give up? There isn’t one, based on an analysis of eleven studies published to date.2 Lead author of this report, Filippo Migliorini, M.D., of Germany, comments, “… the dose of duloxetine must be customized according to the individual patient, and the response to treatment could be genetically determined.”

In case you are in the group that responds to duloxetine, or your doctor prescribes this drug for either mood or anxiety, below are strategies for giving this drug a try.

Overcoming Side Effects

The most common early side effects include nausea, dry mouth, constipation, fatigue, sleepiness, increased sweating, and decreased appetite. Lesley Arnold, M.D. of the University of Cincinnati College of Medicine, in Ohio, and lead investigator for several duloxetine trials in fibromyalgia, offers suggestions to counter the side effects.3

Reducing Nausea: Arnold recommends that patients start the medication at a lower dose of 30 mg/day for at least the first week and maybe longer before increasing to 60 mg/day. She also instructs patients to take the medication with food, preferably after their first full meal of the day. The nausea reported by study participants was generally mild to moderate and subsided for most patients within one to two weeks.

Dry Mouth and Constipation: Both may lessen in severity with continued use. Arnold recommends sugar-free mints or candy, and to avoid sugary foods as teeth become vulnerable with dry mouth. The constipation can be minimized by increasing fluid and fiber intake, and perhaps using a fiber supplement.

Going off duloxetine: Arnold recommends that patients reduce their dosage slowly to avoid dizziness or other withdrawal symptoms.

What about Blood Pressure?

Due to duloxetine’s ability to increase the action of NE in the central nervous system, it has the potential to increase pulse and blood pressure. It’s the effect on NE that makes these drugs more effective for pain relief than agents that just boost serotonin. The greater the NE action, the more likely the drug will aid with daytime fatigue and minimize weight gain. As with any medication, there are trade-offs. The FDA recommends that patients have their blood pressure and pulse monitored during treatment.

Adjusting for Sleep

The effect of duloxetine on sleep varies. Most patients do not report a change in sleep, yet some encounter daytime sleepiness while others report difficulty falling asleep or staying asleep. In this case, doctors should change when the drug is prescribed to suit the needs of the patient.

If a patient experiences daytime sleepiness or fatigue, Arnold recommends that the patient take duloxetine at dinner time in the evening. She finds that once-a-day dosing works best to relieve pain all day for most patients, but on rare occasions, suggests splitting the dose in two (morning and with dinner) if necessary to make it more tolerable.

“We find that morning dosing works best for patients who experience some sleep disruption when taking duloxetine. We sometimes add another treatment at night if the patient continues to have sleep problems related to fibromyalgia,” says Arnold. “There are some patients who report improved sleep on duloxetine. The key message is to not give up too soon: try different doses and try taking it at different times.

Other Side Effects

The report by Migliorini looking at all the trial data on duloxetine identified additional side effects: headaches, fatigue, loss of appetite, and sweating. Perhaps some of these unwanted symptoms can be minimized by taking duloxetine at bedtime or using a lower dose of the medication. It really is a trial-and-error process with any new drug.

Other Risks

If you are taking more than one medication that raises your central nervous system level of serotonin, you can be at risk of serotonin syndrome. This is a serious toxic consequence of too much serotonin in the body. In addition, doctors also need to check for an elevation in liver enzymes because duloxetine (along with many drugs) has the potential to harm the liver.

1. Hauser W, Fitzcharles MA. Dialogues Clin Neurosci 20:5-61, 2017.
2. Migliorini F, at al. J Orthopaed Surg Res 18:504, 2023.
3. Arnold L. Pain Medicine 8(S2) S63-S74, 2007.