Reviewed on 10/17/2022

What Is Levomilnacipran and How Does It Work?

Levomilnacipran is a prescription medication used for the treatment of major depressive disorder.

  • Levomilnacipran is available under various brand names: Fetzima

What Are Side Effects Associated with Using Levomilnacipran?

Common side effects of Levomilnacipran include:

  • difficulty having a bowel movement,
  • increased sweating,
  • loss in sexual desire,
  • vomiting,
  • abdominal pain,
  • bloating,
  • decreased appetite,
  • dry eyes,
  • dry skin,
  • flushing,
  • severe headache,
  • itching,
  • rash,
  • gas,
  • red eyes,
  • redness of the face, neck, arms, or upper chest,
  • sudden sweating,
  • thirst, and
  • yawning

Serious side effects of Levomilnacipran include:

  • hives,
  • difficulty breathing,
  • swelling of the face, lips, tongue, or throat,
  • difficulty urinating,
  • fast, pounding, or irregular heartbeats,
  • anxiety,
  • arm, back, or jaw pain,
  • loss of balance or coordination,
  • muscle stiffness, trembling or jerking,
  • nausea,
  • blurred vision,
  • painful urinating,
  • numbness or tingling,
  • painful urination,
  • pounding in the ears,
  • chest pain or pressure,
  • rapid or irregular heartbeat,
  • restlessness,
  • cloudy urine,
  • confusion,
  • tremors,
  • little or no urination,
  • difficulty passing urination (dribbling),
  • slow heartbeat,
  • difficulty speaking,
  • sweating,
  • dizziness,
  • lightheadedness,
  • drooling,
  • trouble sleeping (insomnia),
  • weakness,
  • unusual tiredness,
  • uncontrolled muscle movements, especially of the face, neck and back,
  • dry mouth,
  • fainting, and
  • irritability

Rare side effects of Levomilnacipran include:

  • none

Seek medical care or call 911 at once if you have the following serious side effects:

  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.


Learn to Spot Depression: Symptoms, Warning Signs, Medication See Slideshow

What Are Dosages of Levomilnacipran?

Adult dosage

Capsule, extended-release

  • 20 mg
  • 40 mg
  • 80 mg
  • 120 mg

Titration packs

  • Contains two 20mg capsules and twenty-six 40mg capsules

Major Depressive Disorders

Adult dosage

  • 20 mg orally every day for 2 days initially; THEN
  • Increase to 40 mg orally every day

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”

What Other Drugs Interact with Levomilnacipran?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Levomilnacipran?


  • Hypersensitivity
  • MAOIs
  • Do not use MAOIs intended to treat psychiatric disorders with levomilnacipran or within 7 days of stopping levomilnacipran due to an increased risk of serotonin syndrome
  • Do not initiate levomilnacipran within 14 days of stopping an MAOI
  • Starting in a patient who is being treated with MAOIs such as linezolid or IV methylene blue is also contraindicated due to an increased risk of serotonin syndrome
  • If methylene blue or linezolid must be administered for an urgent condition to a patient currently taking a serotonergic drug, stop the serotonergic drug immediately and monitor for CNS toxicity; serotonergic therapy may be resumed 24 hr after the last dose of methylene blue, or after 2 weeks of monitoring, whichever comes first

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Levomilnacipran?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Levomilnacipran?”


  • All patients being treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and when increasing or decreasing the dose; consider changing the therapeutic regimen, including possibly discontinuing therapy, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors
  • SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of other drugs that inhibit platelets or anticoagulants may increase this risk; inform patients about the risk of bleeding associated with concomitant use of drug and NSAIDs, aspirin, or other drugs that affect coagulation
  • Risk of mydriasis; may trigger angle closure attack in patients with angle-closure glaucoma with anatomically narrow angles without a patent iridectomy; pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy; open-angle glaucoma is not a risk factor for angle-closure glaucoma
  • Can affect urinary hesitation or retention; caution with obstructive urinary disorders and discontinue if symptoms present; the noradrenergic effect of the drug can affect urethral resistance; if symptoms of urinary hesitation, urinary retention, or dysuria develop during treatment, consideration should be given to the possibility that they might be drug-related, and discontinuation or other appropriate medical intervention should be considered
  • May activate mania/hypomania in patients with bipolar disorder; screen patients for bipolar disorder prior to initiating; use cautiously in patients with a history or family history of bipolar disorder, mania, or hypomania
  • Caution with seizure disorders; not systematically evaluated in patients with a seizure disorder
  • Sexual dysfunction
    • Use may cause symptoms of sexual dysfunction in both male and female patients; inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider
    • Use of SSRIs may cause symptoms of sexual dysfunction; in male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction
    • In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm
    • Important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment because the sexual function may not be spontaneously reported
    • When evaluating changes in sexual function, obtaining a detailed history (including the timing of symptom onset) is important because sexual symptoms may have other causes, including underlying psychiatric disorder
    • Discuss potential management strategies to support patients in making informed decisions about treatment
  • Serotonin syndrome
    • Potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs both when taken alone, but especially when coadministered with other serotonergic agents; thoroughly review patient medications for other serotonergic drugs (eg, tryptophan supplements, tramadol, 5-HT agonists [triptans], MAOIs, TCAs, SSRIs)
    • Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea)
    • Monitor all patients receiving therapy for the emergence of serotonin syndrome; discontinue treatment with the drug and any concomitant serotonergic agents immediately if the above events occur and initiate supportive symptomatic treatment; if concomitant use of the drug with other serotonergic drugs is clinically warranted, inform patients of increased risk for serotonin syndrome and monitor for symptoms
  • Blood pressure
    • May increase blood pressure; blood pressure should be measured prior to initiating treatment and periodically throughout treatment
    • Pre-existing hypertension should be controlled before initiating therapy
    • Use caution when treating patients with pre-existing hypertension, cardiovascular, or cerebrovascular conditions that might be compromised by increases in blood pressure
    • For patients who experience a sustained increase in blood pressure while receiving drugs, discontinuation or other appropriate medical intervention should be considered
  • Heart rate
    • Therapy may increase heart rate; heart rate should be measured prior to initiating treatment and periodically throughout treatment
    • Pre­existing tachyarrhythmias and other cardiac diseases should be treated before starting therapy; for patients who experience a sustained increase in heart rate while receiving therapy, discontinuation or other appropriate medical intervention should be considered
    • The drug has not been systematically evaluated in patients with a cardiac rhythm disorder
  • Discontinuation syndrome
    • Discontinuation symptoms (some serious) were reported with abrupt withdrawal of serotonergic antidepressants
    • Some symptoms include dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures
    • Monitor patients for these symptoms when discontinuing therapy; reduce the dose gradually whenever possible; if intolerable symptoms occur following a decrease in dose or upon discontinuation of treatment, consider resuming the previously prescribed dose; subsequently, the dose may be decreased, but at a more gradual rate
  • Hyponatremia
    • Hyponatremia may occur; in many cases, hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH); cases with serum sodium lower than 110 mmol/L reported
    • Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs; patients taking diuretics or who are otherwise volume-depleted can be at greater risk
    • Therapy should be discontinued in patients with symptomatic hyponatremia and appropriate medical intervention instituted
    • Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls
    • Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death
  • Drug interaction overview
    • Contraindicated with an MAOI (or within 14 days of stopping an MAOI) intended to treat psychiatric disorders or within 7 days of stopping treatment with levomilnacipran; it is also contraindicated in patients treated with linezolid or IV methylene blue
    • Coadministration with strong CYP3A4 inhibitors may increase levomilnacipran levels; see Dosage Modifications
    • Avoid alcohol with levomilnacipran; concomitant use may result in the accelerated release of levomilnacipran from the extended-release capsules
    • SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events; coadministration with other antiplatelet drugs or anticoagulants may cause additive risk
    • Coadministration with other serotonergic drugs may increase the risk of serotonin syndrome

Pregnancy & Lactation

  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants
  • Available data on pregnant women are insufficient to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; there are risks associated with untreated depression in pregnancy and with exposure to SNRIs and SSRIs during pregnancy
  • Clinical considerations
    • Women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants; consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum
    • Use of SNRIs in late pregnancy may be associated with an increased risk of postpartum hemorrhage
  • Fetal/neonatal effects
    • Neonates exposed to SNRIs or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; such complications can arise immediately upon delivery
    • Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, constant crying
  • Lactation
    • There are no available data on the presence of the drug in human milk; however, racemic milnacipran is present in human milk; there are no reports on the effects of the drug or milnacipran on breastfed infants or effects on milk production; however, there are reports of agitation, irritability, poor feeding and poor weight gain in infants exposed to SSRIs or SNRIs through breast milk
    • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from drugs or from underlying maternal conditions
  • Clinical considerations
    • Infants exposed to the drug should be monitored for agitation, irritability, poor feeding, and poor weight gain.


Depression is a(n) __________ . See Answer

Health Solutions From Our Sponsors