Duloxetine for Pain
Navigating the Side Effects
Duloxetine (Cymbalta) treats depression and generalized anxiety disorder, but it can relieve fibromyalgia pain independent of mental health. In fact, it was approved by the Food and Drug Administration (FDA) for fibromyalgia in 2008.
How does duloxetine work? It’s thought to treat pain by increasing the availability of serotonin and norepinephrine (NE) in the central nervous system. These two chemical transmitters are used by your neurons to 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 shows that both serotonin and NE are in short supply in the nervous system of fibromyalgia patients. So, taking duloxetine makes sense.
Duloxetine is in a drug class called selective serotonin NE reuptake inhibitors or SNRIs. When serotonin and NE are released at the nerve endings, SNRIs 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 like duloxetine “recycle” the two transmitters that are low in most fibromyalgia patients.
What are the Odds?
In theory, duloxetine sounds like a good drug for fibromyalgia, but what are the odds that it helps? Also, how long do you have to take the drug before you notice pain reduction? And what about dose – is there a set dose that works best for most patients with fibromyalgia?
The trials for duloxetine’s FDA-approval showed the drug worked in 15-20 percent of people with fibromyalgia. However, these trials only included patients with mild symptoms. For the typical fibromyalgia patient with moderate symptoms, duloxetine works in one out of ten patients.1 In fact, this is the same odds of achieving treatment success with any of the FDA-approved drugs for fibromyalgia.
Given the low success rate for duloxetine, is there a way to predict responders to the drug? Yes, but it requires a two-week trial. If you do not notice significant reductions in pain after two weeks, the chances of the drug working are only 15 percent.2
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.3 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.”
One more fact you should know about duloxetine: one out of five fibromyalgia patients are prescribed this drug.4 Yet side effects and lack of efficacy force 50 percent of patients to discontinue the drug during the first year.5
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, offers suggestions to counter the side effects.6 She was the lead investigator for several trials involving duloxetine for treating fibromyalgia pain.
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 caused by duloxetine is mild to moderate and subsides within one to two weeks for most fibromyalgia patients.
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. In addition, 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.
Duloxetine & 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 duloxetine 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. However, 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 taking duloxetine at dinner time. 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 fibromyalgia patients who report improved sleep on duloxetine. The key message is to not give up too soon: try different doses and try taking the drug at different times. Alternatively, you can ask your doctor about a nighttime prescription of pregabalin or gabapentin to help with sleep.
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. 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, beware 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) may potentially harm the liver.
Add-on Therapies
Controlling fibromyalgia symptoms requires more than one treatment approach. The following sources can help:
- Other drug options: see Medications
- Nondrug or alternative therapies: see Nondrug Treatments
- Self-help techniques to reduce muscle pain: see Muscle Pain Relief
- Fibro-friendly advice on staying fit: see Movement Therapies
- Adjusting your diet: see Diet & Nutrition
Stay Current on Treatments & Research News: Sign up for a Free Membership to automatically be alerted about new postings to this site. Just click on the dark purple button at the top of the page to provide your name and email.
Duloxetine for Fibromyalgia References
- Hauser W, Fitzcharles MA. Dialogues Clin Neurosci 20:5-61, 2017. Free Report
- Wang F. et al. J Pain 12(10):1088-94, 2011. Free Report
- Migliorini F, at al. J Orthopaed Surg Res 18:504, 2023. Free Report
- Rico-Villademoros F, et al. Clin Exp Rheum 38(Suppl 123):S72-S78, 2020. Free Report
- Liu Y, et al. J Manag Care Spec Pharm 22(3):263-71, 2016. Free Report
- Arnold LM. Pain Medicine 8(S2) S63-S74, 2007. Free Report