Levomilnacipran (Fetzima): dosage, uses, side effects

If you’ve been struggling with depression for a while, you may have tried different approaches to get your symptoms under control. Talk therapy, exercise, yoga, meditation, and changing your diet are all options that can help some people feel better. But for others, it isn’t enough. 

Your healthcare provider may recommend adding an antidepressant to your treatment plan. Depression is a complex disease, but chemical imbalances in the brain play a role. Find out how Fetzima can affect these brain chemicals and what you should know before starting treatment. 

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Fetzima (levomilnacipran) is a medication used to treat depression. Fetzima belongs to a group of antidepressants called serotonin-norepinephrine reuptake inhibitors, or SNRIs for short (Allergan, 2021). SNRIs increase brain levels of serotonin and norepinephrine—two neurotransmitters or chemicals that deliver signals from one part of the body to another. Researchers believe that low levels of serotonin and norepinephrine contribute to depression. SNRIs help correct this imbalance (Sahli, 2016). 

Fetzima is approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in adults. Unlike other SNRIs, Fetzima has not been studied to treat fibromyalgia and should not be used for this purpose (Allergan, 2021). 

If you’ve just started treatment with Fetzima, you’re probably anxious to start feeling better. Keep in mind that Fetzima, like all antidepressant medications, takes time to work. Some people will notice an improvement in their symptoms within the first two weeks, but it can take up to eight weeks to get the full benefits. So don’t get discouraged if you aren’t feeling better right away (Allergan, 2021; Machado-Vieira, 2010). 

The most common side effect of Fetzima is nausea. Taking your dose with food may help. Other common adverse effects include (Allergan, 2021):

• Constipation

• Erectile dysfunction

• Fast or abnormal heartbeat

• Sweating 

• Vomiting 

Rarely, Fetzima may cause serious side effects. Certain conditions increase your risk of developing these reactions. Be sure to review the warnings associated with Fetzima (see below) and let your healthcare provider know if you experience any severe symptoms. 

Fetzima is available in doses of 20 mg, 40 mg, 80 mg, and 120 mg extended-release capsules. The typical starting dose is 20 mg once daily. Your healthcare provider may increase your dose to a maximum of 120 mg daily, depending on your symptoms and side effects (Allergan, 2021). 

Because Fetzima is an extended-release capsule, you should swallow your dose whole. Do not open, chew, or crush the capsule—doing so can release the medication into your body too quickly and increase your risk of side effects (Allergan, 2021).

Fetzima is associated with several warnings. It is important to review these warnings before starting Fetzima and discuss any concerns with your healthcare provider. Knowing the warning signs to watch out for and reporting any symptoms can help keep you safe.

Suicidal thoughts and behaviors 

All antidepressants, including Fetzima, carry a boxed warning (the FDA’s strongest warning) regarding the risk of suicidal thoughts and behaviors in children and young adults. Studies have not shown an increased risk in people over the age of 24. Regardless, the FDA urges that all people started on an antidepressant be monitored for worsening symptoms and suicidal thoughts and behaviors, especially during the first few months of treatment. It is important to remember that untreated depression also is associated with risks. You and your healthcare provider will discuss these risks and determine your best course of treatment (Allergan, 2021). 

Serotonin syndrome 

Because Fetzima affects serotonin levels, there is a risk of developing serotonin syndrome—a potentially life-threatening condition that occurs when serotonin levels in the brain become too high. Your risk of serotonin syndrome increases if you also take other medications that affect serotonin levels (e.g., other antidepressants or certain pain medications). The symptoms of serotonin syndrome can progress quickly, so it’s important to seek medical care if you develop any of the following (Allergan, 2021): 

• Agitation or restlessness 

• Changes in blood pressure 

• Confusion 

• Diarrhea 

• Dizziness 

• Increased heart rate 

• Fever 

• Flushing 

• Hallucinations 

• Muscle stiffness or muscle spasms 

• Nausea or vomiting 

• Nervousness 

• Seizures 

• Sweating 

• Tremor 

• Trouble sleeping 

• Trouble with balance or coordination 

Discontinuation syndrome

If you’re considering stopping Fetzima, talk with your healthcare provider first. Abruptly stopping treatment may cause withdrawal-type reactions, which can sometimes be serious. Your healthcare provider will likely recommend a plan that involves slowly decreasing your dose to help limit these reactions. Withdrawal symptoms include (Allergan, 2021):

• Anxiety 

• Changes in your mood 

• Confusion 

• Dizziness

• Electric shock sensations 

• Headaches

• Irritability and agitation 

• Nausea

• Problems sleeping 

• Ringing in your ears

• Seizures 

• Sweating 

• Tiredness 

Sexual dysfunction

Fetzima may cause sexual problems in both men and women, including decreased sex drive, inability to orgasm, or trouble getting or maintaining an erection. It's normal to feel uncomfortable discussing these problems with your healthcare provider, but don’t hesitate to let them know since they may be able to offer treatment that can help (Allergan, 2021). 

Increased blood pressure and heart rate

Fetzima can increase blood pressure or heart rate (tachycardia) in some people. Let your healthcare provider know if you have high blood pressure (hypertension) or any heart problems. These conditions must be controlled before starting Fetzima (Allergan, 2021). 

Increased risk of bleeding 

Fetzima may increase your risk of bleeding, especially if you take aspirin, NSAIDs (like ibuprofen or naproxen), or blood thinners. Let your healthcare provider know if you notice any signs of unusual bruising or bleeding (Allergan, 2021). 

Eye problems

Rarely, Fetzima may cause an eye problem called angle-closure glaucoma. Contact your healthcare provider if you develop eye pain or problems with your vision (Allergan, 2021). 

Trouble urinating 

Problems with urination, including decreased urine flow and inability to urinate, have sometimes occurred with Fetzima. Let your healthcare provider know if you experience any changes (Allergan, 2021). 

Manic episodes 

Let your healthcare provider know if you or a family member have been diagnosed with bipolar disorder, mania, or hypomania. Fetzima may increase your risk of developing a manic episode. Symptoms include increased energy levels, racing thoughts, talking more or faster than normal, trouble sleeping, and excessive happiness or irritability (Allergan, 2021). 

Seizures

Fetzima should be used cautiously in people with seizure disorders. Let your healthcare provider know if you’ve experienced seizures in the past (Allergan, 2021). 

Low sodium levels

Fetzima can cause sodium levels in your blood to become too low, which can sometimes cause serious effects. You may be at increased risk if you are older or take diuretics (sometimes called “water pills”). Signs of low sodium include headache, difficulty concentrating, confusion, and weakness. Very low sodium can cause hallucinations, seizures, fainting, and even coma (Allergan, 2021). 

Pregnancy and breastfeeding 

Taking Fetzima towards the end of your pregnancy may increase the risk of your baby experiencing certain complications after delivery. It can also increase your risk of excessive bleeding after delivery (postpartum hemorrhage). However, untreated depression can also negatively affect you and your baby’s health. You and your healthcare provider will discuss these risks and determine your best treatment (Allergan, 2021). 

It is unknown if Fetzima is present in breast milk. Talk with your healthcare provider about the best way to feed your baby. If you decide to breastfeed, monitor your baby for sleepiness, irritability, and appropriate weight gain (Allergan, 2021). 

Fetzima may interact with other medications you take. Be sure to let your healthcare provider know about all your medicines, including over-the-counter natural products and supplements. 

Keep an eye out for these common drug interactions:

MAOIs (monoamine oxidase inhibitors) should never be taken with Fetzima. Combining these medications greatly increases your risk of serotonin syndrome. Don’t start Fetzima within 14 days of stopping an MAOI used for depression, and don’t start an MAOI antidepressant within seven days of stopping Fetzima (Allergan, 2021). 

MAOIs include:

• Isocarboxazid (Marplan) 

• Linezolid (Zyvox)

• Phenelzine (Nardil) 

• Rasagiline (Azilect) 

• Selegiline (Emsam, Zelapar) 

• Tranylcypromine (Parnate) 

• Intravenous (IV) methylene blue 

Other medications can also increase your risk of developing serotonin syndrome. Let your healthcare provider know if you take (Foong, 2018):

• Other SNRIs like duloxetine (Cymbalta), desvenlafaxine (Pristiq), and venlafaxine (Effexor XR) 

• SSRIs (selective serotonin reuptake inhibitors), such as paroxetine (Paxil), fluoxetine (Prozac), escitalopram (Lexapro), citalopram (Celexa), and sertraline (Zoloft)

• TCAs (tricyclic antidepressants) like clomipramine (Anafranil) and imipramine 

• Cough and cold products that contain dextromethorphan (“DM”) and chlorpheniramine 

• Natural health supplements like St. John’s wort, L-tryptophan, and diet pills 

• Drugs of abuse, such as ecstasy (MDMA), amphetamine, and cocaine 

Alcohol increases how much Fetzima your body absorbs. Do not consume alcohol while taking Fetzima (Allergan, 2021). 

Certain drugs can increase your risk of bleeding with Fetzima. Watch out for (Allergan, 2021): 

• Aspirin 

• NSAIDs like ibuprofen or naproxen 

• Blood thinners like warfarin, apixaban (Eliquis), or rivaroxaban (Xarelto)

• Antiplatelet drugs like clopidogrel (Plavix) or ticagrelor (Brilinta) 

Some medications may increase levels of Fetzima. Your healthcare provider may recommend a lower dose of Fetzima if you take (Allergan, 2021):

• Certain HIV medications 

• Clarithromycin 

• Antifungal medications like ketoconazole, voriconazole, or itraconazole 

This is not a complete list of all the drugs that may interact with Fetzima. Always ask your healthcare provider or pharmacist before starting anything new. 

Seeking help for your depression can be hard, but it's the first step to getting you well. If starting an antidepressant is part of your plan, your healthcare provider may recommend Fetzima. Be sure to let your healthcare provider know about any side effects you experience. They may be able to adjust your dose or offer other treatment that allows you to continue using Fetzima safely. 

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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 11, 2021

Written by

Christina Varvatsis, PharmD

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.