Milnacipran (Savella): dosage, uses, side effects

Fibromyalgia is a common chronic pain disorder with complex symptoms. It can sometimes be challenging to find consistently effective treatments for fibromyalgia. Could Savella be a good choice for you? Read on to find out.

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Savella is a drug used to treat fibromyalgia. The generic name of Savella is milnacipran. Savella is also sold outside the United States under the names Ixel, Dalcipran, and Toledomin.

Savella is a type of drug called a serotonin-norepinephrine reuptake inhibitor (SNRI). These drugs work by blocking the reabsorption (reuptake) of the neurotransmitters serotonin and norepinephrine back into the nerve cells that released them. This action increases the levels of active neurotransmitters in the brain.

Savella is approved by the FDA for the treatment of fibromyalgia, a condition that causes chronic pain throughout the body, as well as sleep problems, fatigue, and often emotional and mental distress. In some other countries, the active ingredient in Savella (milnacipran) is approved to treat major depressive disorder but not fibromyalgia. Savella isn’t approved to treat depression in the United States (Häuser, 2018; Derry, 2015).

A review of six clinical trials of Savella for fibromyalgia, which included over 4,200 participants in total, found that Savella provided moderate levels of pain relief for fibromyalgia for about 40% of the people involved in the review (compared to 30% for placebo). That’s an impressive result, especially for a difficult-to-treat condition like fibromyalgia—but it’s not all sunshine and roses. Savella can come with some side effects bothersome enough to have caused about 20% of the participants to withdraw from the studies. Serious side effects were rare (Cording, 2015).

The most common adverse events of Savella include (FDA, 2021):

• Nausea

• Headache

• Constipation

• Dizziness

• Insomnia

• Hot flush

• Sweating

• Vomiting

• Fast or irregular heartbeat (palpitations)

• Dry mouth

• High blood pressure

Savella comes in 12.5 mg, 25 mg, 50 mg, and 100 mg tablets. The typical recommended dose of Savella is 100 mg/day, although your healthcare provider will determine what is right for you. Usually, it’s taken in two divided doses a day (meaning, you take half in the morning and half in the evening). Based on how well Savella is working, its side effects, and any other drugs you may be taking, your healthcare provider may start you with a single 12.5 mg dose, gradually increasing the dose over one week, to 100 mg per day. The dose may be increased to 200 mg/day for some patients, depending on their response to the drug (FDA, 2021).

While mild (but bothersome!) side effects happen pretty commonly with Savella, two primary severe side effects can happen in rare cases, too.

Suicidal thoughts and behaviors 

Savella comes with a box warning from the FDA for its potential to cause suicidal thoughts and behaviors in people 24 and under. This side effect is usually more of a concern at the start of treatment. If you start taking milnacipran, your loved ones will need to monitor you for changes in behavior. 

Serotonin syndrome

Savella is a drug that affects serotonin levels, and serious interactions can occur when it’s combined with other medications that also affect serotonin levels. When you have too much serotonin in your body, it can lead to serotonin syndrome, a condition that can include changes in mental status (such as agitation, hallucinations, and coma), effects on the nervous system (such as fast heart rate, changes in blood pressure, and dizziness), impairment of muscular control (such as rigidity, lack of coordination), seizures, and gastrointestinal symptoms (such as nausea, vomiting, and diarrhea) (FDA, 2021).

Savella is only slightly metabolized by the body. Most of the drug passes out of the body in urine, so interactions with many other drugs are unlikely.

However, because Savella is a serotonergic drug, serious interactions can occur when it’s combined with other medications that affect serotonin levels. These drugs include (FDA, 2021):

• Monoamine oxidase inhibitors (MAOIs), such as linezolid and methylene blue

• Tramadol

• Triptans (serotonin agonists), such as eletriptan, frovatriptan, and lasmiditan

• Catecholamines, such as epinephrine and norepinephrine

• Tricyclic antidepressants (TCAs), such as amitriptyline, clomipramine, and doxepin

• Other SNRIs, such as venlafaxine (Effexor), duloxetine (Cymbalta), and levomilnacipran

• Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, escitalopram (Lexapro), and fluoxetine (Prozac)

• Fentanyl

• Buspirone (Buspar)

• Amphetamines

• St. John’s wort

If you’re interested in taking Savella, be sure to tell your healthcare provider about any drugs and supplements you’re taking.

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Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

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Current version

November 17, 2021

Written by

Alison Dalton

Fact checked by

Steve Silvestro, MD

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About the medical reviewer

Steve Silvestro, MD, Ro

Dr. Steve Silvestro is a board-certified pediatrician and Associate Director, Clinical Content & Education at Ro.