What is Savella (milnacipran)?

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Last updated: April 25, 2025View editorial policy

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From the Guidelines

Savella is a prescription medication with the generic name milnacipran, primarily used to treat fibromyalgia in adults, as supported by the most recent evidence from 1 and 1. It belongs to a class of drugs called serotonin and norepinephrine reuptake inhibitors (SNRIs), which work by increasing the levels of these neurotransmitters in the brain to help reduce pain and improve mood. The typical starting dose is 12.5 mg once daily, gradually increasing to a target dose of 50 mg twice daily, though some patients may require up to 100 mg twice daily, as indicated in the studies 1 and 1. Some key points to consider when prescribing Savella include:

  • Patients should take Savella with food to improve tolerance and follow their doctor's titration schedule to minimize side effects.
  • Common side effects include nausea, headache, constipation, dizziness, and increased sweating.
  • Savella is not approved for treating depression in the United States, though it may be used for this purpose in other countries.
  • People with uncontrolled narrow-angle glaucoma, severe kidney disease, or those taking MAO inhibitors should not take Savella, and the medication should not be stopped abruptly as withdrawal symptoms may occur, as noted in 1 and 1. The most recent and highest quality study, 1, provides guidance on the management of fibromyalgia, including the use of SNRIs like milnacipran, and highlights the importance of careful consideration of the benefits and risks of treatment. Additionally, the study 1 provides an overview of the results from selected systematic reviews of placebo-controlled pharmacological trials, including those involving SNRIs like milnacipran, and notes the importance of evaluating the quality of the evidence and the potential for adverse effects. Overall, the use of Savella for the treatment of fibromyalgia should be guided by the most recent and highest quality evidence, and should take into account the individual patient's needs and circumstances, as supported by 1 and 1.

From the FDA Drug Label

Milnacipran hydrochloride is a selective norepinephrine and serotonin reuptake inhibitor; it inhibits norepinephrine uptake with greater potency than serotonin. Milnacipran, also known by its brand name Savella, is a medication that acts as a selective norepinephrine and serotonin reuptake inhibitor. It is used to treat certain conditions, including fibromyalgia. The exact mechanism of its action is unknown, but it is believed to work by inhibiting the reuptake of norepinephrine and serotonin in the brain, which can help to improve symptoms of fibromyalgia. 2

From the Research

Definition and Mechanism of Savella

  • Savella, also known as milnacipran, is a serotonin and norepinephrine reuptake inhibitor (SNRI) 3, 4, 5, 6.
  • It has a unique pharmacokinetic and pharmacodynamic profile, with equipotent serotonin and norepinephrine reuptake inhibition and a linear dose-concentration trend at therapeutic doses 4.
  • Milnacipran acts by decreasing pain transmission, making it an effective treatment option for fibromyalgia 5.

Uses of Savella

  • Savella is approved by the FDA for the treatment of fibromyalgia in adults 3, 5.
  • It is also used as an antidepressant, particularly for patients with depression and pain, and those with endogenous depression characterized by anergia, psychomotor retardation, and hypersomnia 6.
  • Milnacipran may be useful for patients with chronic pain, fatigue, and sleep disturbances 7.

Efficacy and Safety of Savella

  • Clinical studies have shown that milnacipran is effective in reducing pain and improving symptoms of fibromyalgia, with significant improvements in pain, global status, and physical function 3.
  • The drug has a relatively safe profile, with most adverse events being mild to moderate in severity and related to its intrinsic pharmacologic properties 3.
  • However, caution is necessary when using milnacipran in patients with heart disease, hypertension, renal impairment, epilepsy, glaucoma, bipolar disorder, and bleeding tendency 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Milnacipran: beyond a role of antidepressant.

Clinical neuropharmacology, 2009

Research

Milnacipran for the Treatment of Fibromyalgia.

Health psychology research, 2021

Research

Milnacipran: serotonin-noradrenaline reuptake inhibitor approved for fibromyalgia may be a useful antidepressant.

Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 2018

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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