Dr. Jenni Jacobsen, PhD
Author: Dr. Jenni Jacobsen, PhD Medical Reviewer: Morgan Blair Last updated:

Levomilnacipran is an antidepressant drug belonging to a class called serotonin-norepinephrine reuptake inhibitors (SNRIs). While this medication can be effective, it’s important to follow safety precautions, as it can come with side effects [1] [2].

Levomilnacipran brand names

In the United States, levomilnacipran is marketed under the brand name Fetzima [2].

What is levomilnacipran prescribed for?

As an antidepressant medication, levomilnacipran is prescribed primarily for the treatment of major depressive disorder. Research has found that it is more effective than a placebo for short-term depression treatment. It has also been found to improve overall functioning and social life in individuals with depression [3].

While not FDA-approved for this purpose, levomilnacipran may sometimes be used to treat anxiety as well. SNRI drugs such as levomilnacipran have been demonstrated to have benefits for individuals with anxiety disorders, including generalized anxiety disorder [4].

How does levomilnacipran work?

Levomilnacipran belongs to a class of drugs called SNRIs. These medications work by blocking the reuptake of serotonin and norepinephrine, two neurotransmitters involved in mood. When the reuptake of these neurotransmitters is blocked, they are available in larger concentrations to stimulate nerve cells. Levomilnacipran is more selective in the reuptake of norepinephrine compared to serotonin [1].

How is levomilnacipran usually taken?

Levomilnacipran is a capsule that is taken by mouth. It is available in doses of 20 mg, 40 mg, 80 mg, and 120 mg. It is recommended that patients begin with a 20 mg dose taken once per day for two days. After that time, the dose can be increased to 40 mg. Depending on how well a patient tolerates the dose, as well as the effectiveness of a particular dose of levomilnacipran, doses can be increased in 40 mg increments every two days, up to a maximum dose of 120 mg taken once daily [2].

How long does levomilnacipran stay in your system?

Levomilnacipran has a half-life of 12 hours. A half-life is the amount of time it takes for half of the initial amount of a drug to be eliminated from the system. The majority of a drug is eliminated from the body after 4 to 5 half-lives, meaning that it takes 48 to 60 hours for levomilnacipran to leave the system [2] [5].

Levomilnacipran side effects

If your doctor has prescribed levomilnacipran, it is because they believe the benefits of this medication will outweigh the risks for you. That being said, the medication can come with adverse effects. These are generally mild and will improve with time, but if side effects are severe or persistent, talk with your doctor.

The most common side effects associated with levomilnacipran include [6]:

  • Nausea and vomiting
  • Orthostatic hypotension (low blood pressure when standing up after being seated)
  • Constipation
  • Sweating
  • Elevated heart rate or palpitations
  • Trouble urinating
  • Decreased appetite
  • Sexual dysfunction(including erectile dysfunction or difficulty with orgasm)

Serious, but rare side effects arising from levomilnacipran use include [6]:

  • Development of a potentially fatal condition called serotonin syndrome, which results in shivering, diarrhea, confusion, musclerigidity, fever, and  
  • Elevated blood pressure
  • Low sodium levels, resulting in headache, weakness, and difficulty
  • Angle-closureglaucoma, a condition that causes eye pain and swelling and changes in vision. 

Contact your doctor immediately if you experience severe side effects from levomilnacipran.

Levomilnacipran precautions

Certain people should not take levomilnacipran, and there are some precautions to consider when taking this medication. Consider the following safety measures [2] [6] :

  • Children, teens, and young adults who take levomilnacipran may be at increased risk of suicidal thinking and behavior when taking this medication. It’s important to be aware of this concern anddiscuss any thoughts of suicide with your treatment provider.
  • Alcohol and illegal drugs should not be used in combination with levomilnacipran, as they can increase the sedative effects of the medication and decrease its effectiveness.
  • If you’re pregnant, breastfeeding, or planning to become pregnant, it’s important to discuss this with your doctor before starting levomilnacipran. Antidepressant medications can have a negative effect on a pregnancy and may be transmitted to the baby in breast milk, so it’s critical to weigh the risks and benefits.
  • Patients with kidney disease should reduce their dosage to prevent additional renal impairment. Levomilnacipran is not recommended for those with end-stagekidney disease.

Levomilnacipran interactions

Levomilnacipran should not be taken with certain medications, as it can cause interaction effects. While this list is not exhaustive, the following medications are known to cause potentially dangerous interaction effects when taken in combination with levomilnacipran [2] [6]:

  • Monoamine oxidase inhibitors (MAOIs): MAOIs including phenelzine, tranylcypromine, isocarboxazid, and selegiline should not be taken in combination with levomilnacipran, as the combination of these two medications can cause symptoms serotonin syndrome. Levomilnacipran should not be used within 14 days after stopping the use of MAOIs.
  • Medications that increase serotonin: Any medication that increases serotonin levels can increase the risk serotonin syndrome when taken alongside levomilnacipran. Medications in this category include other antidepressants, such as fluoxetine or paroxetine, as well as pain medications like tramadol, antibiotics including linezolid, and migraine medications including Imitrex.
  • Antifungals: Antifungal medications including fluconazole, ketoconazole, and itraconazole can elevate levels of levomilnacipran and cause dangerous interaction effects.
  • Drugs that increase bleeding: Drugs like warfarin and aspirin, which can increase bleeding, should not be taken alongside levomilnacipran. Anti-inflammatory drugs like ibuprofen and naproxen can also increase the risk of bleeding events with levomilnacipran.
  • Antibiotics: Clarithromycin and azithromycin, both of which are commonly prescribed antibiotics, can interact with levomilnacipran.
  • Antiarrhythmic drugs: The antiarrhythmic drug quinidine can increase the effects of levomilnacipran.
  • HIV medications: Finally, HIC medications including indinavir, ritonavir, saquinavir, and lopinavir/ritonavir can elevate levomilnacipran levels and cause dangerous druginteraction effects.

Levomilnacipran storage

Your medication should be stored at room temperature. Excessive heat can cause damage to the medication, so it should not be stored in the bathroom [2]. Keep levomilnacipran out of the reach of children and in its original container to avoid unintentional poisoning.

What to do if you overdose on levomilnacipran

If you believe you have overdosed on levomilnacipran, contact 911 or the Poison Control Center immediately. You will require emergency medical attention to ensure your safety [6] [7] [8].

Levomilnacipran alternatives

There are alternative antidepressant medications in the SNRI class, including duloxetine, venlafaxine, desvenlafaxine, and milnacipran. If you do not experience symptom relief with levomilnacipran, your doctor may choose another medication in the SNRI class. You may need to try a few medications before you find one that works best for you [1].

Beyond these medications, there are other classes of antidepressant drugs that may be more effective for you, including [1][7] [8]:

Your doctor or healthcare provider will help you to determine the best medication for your situation.

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Dr. Jenni Jacobsen, PhD
Author Dr. Jenni Jacobsen, PhD Medical Reviewer, Writer

Dr. Jenni Jacobsen, PhD is a medical reviewer, licensed social worker, and behavioral health consultant, holding a PhD in clinical psychology.

Published: Oct 6th 2023, Last edited: Oct 26th 2023

Morgan Blair
Medical Reviewer Morgan Blair MA, LPCC

Morgan Blair is a licensed therapist, writer and medical reviewer, holding a master’s degree in clinical mental health counseling from Northwestern University.

Content reviewed by a medical professional. Last reviewed: Oct 6th 2023