Milnacipran for fibromyalgia

The full story

Fibromyalgia (FM) is a poorly understood condition that affects muscles, ligaments, and tendons. It is characterized by chronic widespread pain and tenderness in muscles and joints. Its exact cause has not been identified, but research suggests that the central nervous system (CNS) in FM patients overreacts to painful stimuli and exaggerates the sensation of pain. 

Unlike other painful conditions, FM does not produce detectable inflammation or abnormal lab tests. Fatigue, sleep disturbances, and difficulty concentrating (“fibro fog”) usually accompany the chronic pain. Up to 50% of people also experience depression or anxiety. Migraine or muscle tension headaches occur in more than 50% of FM patients. 

Although there is no cure for FM, a variety of nondrug and medication-based treatments exist. A combination of different treatment approaches usually works best. Research has shown that physical activity such as aerobic exercise, Tai Chi, and yoga is the most effective treatment for FM. Mindfulness is a type of meditation that eases stress and also significantly improves FM symptoms. Medications for FM are aimed at either increasing brain neurotransmitters involved in pain control (serotonin, norepinephrine) or reducing the hyperactivity of nerves that carry pain signals.

Although other drugs like antidepressants and some plant-based medicines might be prescribed for pain in FM, only three medications are approved by the FDA. Milnacipran (Savella®) and duloxetine (Cymbalta) are serotonin-norepinephrine reuptake inhibitors (SNRIs), which increase the amounts of these pain-controlling chemicals at nerve endings in the brain and spinal cord (CNS). The third FDA-approved treatment for FM is pregabalin (Lyrica®), which is a medication given for seizures that calms excitable nerves in the CNS. None of these drugs have been compared against the others in clinical trials.

Milnacipran was approved by the FDA in 2009 solely for the treatment of FM. It is moderately effective at relieving chronic widespread pain and improving people’s ability to function. It also helps relieve fatigue and bolster thought processes. About half of patients taking milnacipran in clinical studies reported noticing benefits after 1 week of treatment. Although milnacipran is marketed in other countries for the treatment of depression, it is not FDA-approved for this purpose in the United States.

What should someone watch for when taking milnacipran? The most frequent side effects include nausea, headache, and constipation. Rarely, a doctor might discontinue the medication if a person’s heart rate or blood pressure goes up too much with treatment. Liver enzyme blood tests should be watched for increasing levels, which happens rarely. Milnacipran should not be stopped abruptly, but rather tapered down gradually to avoid withdrawal symptoms such as irritability, anxiety, and sleep problems.

Serotonin syndrome can result from mixing drugs like milnacipran with other medications that raise serotonin levels. Many types of antidepressants (SSRIs, SNRIs, bupropion, tricyclics, MAO inhibitors) can add to the serotonin-boosting effects of milnacipran and cause serotonin syndrome, so ask your pharmacist or doctor if you already take an antidepressant. Other medications that might interact this way with milnacipran include some migraine drugs, opioid analgesics, herbal supplements, and cough suppressants. Serotonin syndrome can be severe and cause symptoms like muscle rigidity, fever, confusion, tremors, and seizures and usually requires treatment in a hospital. For more information about the symptoms and which drugs might interact, see "What is serotonin syndrome?"

Normal doses of milnacipran start at 12.5 mg once a day by mouth and are increased slowly to a maximum dose of 100–200 mg daily. There are case reports of people who took larger doses (1000 to 2800 mg) and experienced only vomiting and drowsiness. Rarely, people taking in excess of 3000 mg have developed serious symptoms like increased or decreased blood pressure, heart arrhythmias, loss of consciousness, and cardiac and respiratory arrest.

If you suspect someone has unintentionally taken milnacipran or is experiencing its side effects, use the webPOISONCONTROL^® online tool to get help, or call your poison center at 1-800-222-1222. Whether online or by phone, expert guidance is always free, confidential, and available 24 hours a day.