What Is Levomilnacipran XR?

Levomilnacipran XR is an extended-release prescription medication used to treat major depressive disorder (MDD) in adults. It belongs to a class of drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs) and is sold under the brand name Fetzima.

Originally developed by Forest Laboratories and Pierre Fabre Group, it is now manufactured by AbbVie Inc. The FDA approved Fetzima in 2013, making it one of the newer SNRIs on the market. Levomilnacipran XR is not a controlled substance.

What Is Levomilnacipran XR Used For?

Levomilnacipran XR is FDA-approved for one indication:

• Major Depressive Disorder (MDD) in adults

MDD is more than just feeling sad. It's a persistent condition that affects your mood, energy, sleep, appetite, and ability to function for at least two weeks. Levomilnacipran XR is typically prescribed when other antidepressants — like SSRIs — haven't provided adequate relief, especially when fatigue, low motivation, and difficulty concentrating are prominent symptoms.

Some doctors also prescribe Levomilnacipran XR off-label for anxiety disorders, neuropathic pain, and chronic fatigue associated with depression, though the evidence for these uses is more limited.

What Makes It Different from Other SNRIs?

While Levomilnacipran XR belongs to the same drug class as Duloxetine (Cymbalta), Venlafaxine XR (Effexor XR), and Desvenlafaxine (Pristiq), it has a key difference: it has roughly 15 times greater selectivity for norepinephrine reuptake inhibition compared to serotonin. Other SNRIs are more serotonin-dominant.

This means Levomilnacipran XR may be particularly helpful for patients whose depression features prominent fatigue, low energy, poor concentration, and lack of motivation — symptoms more closely linked to norepinephrine. Learn more in our guide on how Levomilnacipran XR works.

How Is Levomilnacipran XR Taken?

Levomilnacipran XR comes as extended-release capsules in four strengths:

• 20 mg (starter dose)
• 40 mg
• 80 mg
• 120 mg

Typical Dosing Schedule

1. Days 1-2: Start at 20 mg once daily
2. Day 3 onward: Increase to 40 mg once daily
3. Dose adjustments: Your doctor may increase the dose in 40 mg increments at intervals of 2 or more days
4. Target range: 40 mg to 120 mg once daily

Important Dosing Rules

• Take once daily at the same time each day
• Can be taken with or without food
• Swallow capsules whole — do not open, chew, or crush them
• If you miss a dose, take it as soon as you remember. If it's close to your next dose, skip the missed dose.

Dose Adjustments for Kidney Problems

Because Levomilnacipran XR is cleared through the kidneys, patients with renal impairment need lower doses:

• Moderate kidney problems: Maximum 80 mg/day
• Severe kidney problems: Maximum 40 mg/day
• End-stage renal disease: Not recommended

No dose adjustment is needed for liver problems.

Who Should Not Take Levomilnacipran XR?

Levomilnacipran XR is not appropriate for everyone. You should not take it if you:

• Are allergic to levomilnacipran, milnacipran (Savella), or any inactive ingredients in the capsule
• Are taking or have recently taken an MAOI (monoamine oxidase inhibitor) — you must wait at least 14 days after stopping an MAOI before starting Levomilnacipran XR, and at least 7 days after stopping Levomilnacipran XR before starting an MAOI
• Have uncontrolled narrow-angle glaucoma

You should use caution and discuss with your doctor if you have:

• High blood pressure or heart disease
• A history of seizures
• Bipolar disorder
• Bleeding problems or take blood thinners
• Kidney disease

Levomilnacipran XR is not approved for children or adolescents. It carries an FDA boxed warning about increased risk of suicidal thoughts in young adults (ages 18-24). For more on side effects, see our complete side effects guide.

How Much Does Levomilnacipran XR Cost?

The cost of Levomilnacipran XR depends on whether you're getting brand-name or generic, and whether you have insurance:

• Brand-name Fetzima: $458-$520 per month (30 capsules) without insurance
• Generic Levomilnacipran ER: Approximately $150-$400 per month with coupons, depending on pharmacy and strength
• With insurance: Varies widely. Fetzima is typically placed on Tier 3 or Tier 4, meaning higher copays. Many plans require prior authorization and step therapy (trying cheaper antidepressants first).

Ways to Save

• AbbVie Savings Program: Eligible commercially insured patients may pay as little as $10/month for Fetzima (up to 12 fills per year)
• Patient Assistance Programs: AbbVie's Patient Assistance Foundation provides Fetzima at no cost to qualifying uninsured or underinsured patients
• Coupon cards: GoodRx, SingleCare, and other discount programs can reduce the price at many pharmacies

For a full breakdown of savings options, see our guide on how to save money on Levomilnacipran XR.

Final Thoughts

Levomilnacipran XR is a unique SNRI that offers a norepinephrine-focused approach to treating major depression. It's a solid option for patients who haven't responded to SSRIs or other SNRIs, particularly those struggling with fatigue, low motivation, and difficulty concentrating.

While it's generally well-tolerated, it's not the cheapest antidepressant on the market — and it may require some effort to find in stock at your local pharmacy. If you need help locating Levomilnacipran XR or finding the best price, Medfinder can help.

Always work with your doctor to determine if Levomilnacipran XR is the right choice for your specific situation.