Cymbalta vs. Lexapro for Depression: Which Is Better?

Cymbalta (duloxetine) and Lexapro (escitalopram) are antidepressant medications. Though these two medications have some similarities, there are a few key differences.

Read on to learn more about the similarities and differences between Lexapro and Cymbalta and why a healthcare provider may recommend one of these medications over the other to treat depression.

Key Differences Between Cymbalta and Lexapro

Cymbalta and Lexapro are alike and different in many ways. Both are commonly taken to treat depression and anxiety disorders. But Cymbalta is approved to treat other conditions as well.

They also belong to different drug classes, have slightly different mechanisms of action, and may cause different side effects.

Lexapro is a brand-name drug also known by its generic name: escitalopram. It belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs).

Cymbalta, on the other hand, is a brand-name medication also known as duloxetine. It belongs to the serotonin-norepinephrine reuptake inhibitor (SNRI) drug class.

The table below compares key facts about the two medications.

What Are Cymbalta and Lexapro's Uses?

The U.S. Food and Drug Administration (FDA) has approved Lexapro and Cymbalta to treat depression and anxiety. However, Cymbalta has been approved for other uses as well.

Specifically, the FDA approved Lexapro to treat:

• Depression, medically known as major depressive disorder (MDD), in adults and children ages 12 years and older
• Generalized anxiety disorder (GAD) in adults and children ages 7 years and older

Cymbalta’s FDA-approved uses include:

• MDD in adults 
• GAD in adults and children ages 7 years and older
• Pain caused by diabetic peripheral neuropathy in adults 
• Fibromyalgia in adults and children ages 13 years or older
• Chronic (long-term) musculoskeletal pain in adults
  

SSRIs vs. SNRIs: How Do They Work?

All antidepressants work to regulate mood by affecting certain chemicals in the brain, but the exact mechanism of how they work varies by drug class.

Serotonin and norepinephrine are neurotransmitters. Neurotransmitters are chemicals that help neurons (nerve cells) communicate. These neurotransmitters perform key roles in regulating mood, behavior, sleep, and more.

When someone has depression, it may be due to a chemical imbalance in their brain. Without a sufficient amount of serotonin and/or norepinephrine available, neurons may not communicate effectively, leading to difficulty regulating mood and mental health changes.

SSRIs

SSRIs, including Lexapro, work by blocking the reabsorption (reuptake) of serotonin in the brain, making more serotonin available to transmit messages between neurons. This helps to enhance serotonin levels and improve communication between brain cells, which can positively affect mood.

All SSRIs have the same mechanism, but a person may have a better response to one SSRI than another. Other examples of other SSRIs include:

• Celexa (citalopram)
• Prozac (fluoxetine)
• Zoloft (sertraline)

SNRIs

SNRIs, such as Cymbalta, have a similar mechanism but target two neurotransmitters instead of one.

By binding to specific receptors on neurons, SNRIs block serotonin and norepinephrine reuptake, allowing more of these neurotransmitters to stay active in the brain. This helps to improve communication between nerve cells and may help to ease symptoms of depression or anxiety.

All SNRIs work this way. However, same as it is with SSRIs, some people may respond better to one SNRI than another. Examples of other SNRIs include: 

• Effexor XR (venlafaxine)
• Fetzima (levomilnacipran)
• Pristiq (desvenlafaxine)

SSRIs and SNRIs take a couple of weeks to start working, and dose adjustments are often necessary. It’s important to follow up with your prescriber to discuss any changes in your symptoms or dosage.

Which Is More Effective for Depression?

Is Cymbalta or Lexapro better? This question can be tricky to answer because each person may respond differently to each medication.

However, clinical trials provide some information that helps compare the two medications regarding how well they work for treating depression. 

Researchers measure the effectiveness of an antidepressant in clinical trials with various assessment metrics, such as symptom rating scales.

In separate clinical trials, Cymbalta and Lexapro were similarly effective in reducing depression symptoms when compared to a placebo.

Compared to a placebo, taking Cymbalta led to a 10- to 12-point improvement on a depression rating scale after two months of treatment. Similarly, taking Lexapro resulted in a reduction of 12 points compared to placebo after two months.

A head-to-head clinical trial is a better way to measure the relative effectiveness of two medications. A few trials have compared Cymbalta and Lexapro for MDD. Here’s what these studies found:

• One trial compared Cymbalta and Lexapro for MDD. After eight weeks, participants who took Lexapro had a greater reduction in depression symptoms compared to those who took Cymbalta.
• Another study compared Cymbalta and Lexapro over an eight-month period. In this study, both medications led to similar improvements in depression symptoms. The only notable difference in the results was that Lexapro was better at improving sleep-related symptoms.

Meta-analysis is another tool that can help researchers draw conclusions based on data from multiple individual studies.

A 2018 meta-analysis reviewed various studies of Cymbalta and Lexapro to compare the two medications. Overall, the results suggest that Cymbalta and Lexapro are similarly effective in reducing depression symptoms.

Side Effects of Cymbalta vs. Lexapro: Which Is More Tolerable?

Most people can take Cymbalta or Lexapro without having side effects, and if they occur, they’re usually temporary or mild.

Because these medications work similarly in the body, they share many of the same potential side effects.

Mild side effects that are common for Cymbalta and Lexapro include:

• Nausea
• Increased sweating
• Sexual side effects, such as erectile dysfunction, trouble reaching orgasm, or decreased libido

Some mild side effects are unique to one medication. Taking Cymbalta may also result in dry mouth, constipation, and decreased appetite. Those taking Lexapro may experience insomnia or fatigue.

Based on comparative studies, Lexapro is generally a better-tolerated medication and causes fewer side effects than Cymbalta. In head-to-head trials and other studies, more participants stopped taking Cymbalta because of side effects than those who were taking Lexapro.

Warnings

Though rare, taking either Cymbalta or Lexapro may result in severe side effects. Examples include:

• Serotonin syndrome, a dangerous reaction caused by an excess amount of serotonin in the body 
• Seizures
• Increased risk of bleeding
• Impaired ability to operate machinery or vehicles
• Angle-closure glaucoma, an eye condition
• Hypersensitivity, or severe allergic reaction
• Dangerously low sodium levels

Taking Cymbalta may result in additional potentially severe side effects. These include:

• Liver damage
• Impaired blood sugar control
• Low blood pressure when standing up, leading to falls
• Increased blood pressure

Additionally, both Cymbalta and Lexapro carry a boxed warning, the most serious warning the FDA provides.

This warning speaks to the increased risk of suicidal thoughts and behaviors that either medication may cause in children or young adults. They encourage close monitoring for individuals who are starting either Cymbalta or Lexapro for any worsening or emerging suicidal thoughts or behaviors.

Drug Interactions

Lexapro and Cymbalta interact with many other medications. These interactions may limit the medications' effectiveness or raise the risk of side effects.

Cymbalta and Lexapro should not be taken with monoamine oxidase inhibitors (MAOIs), which means they should not be taken at the same time or within 14 days of each other. MAOIs include Marplan (isocarboxazid), Zyvox (linezolid), and methylene blue. Taking MAOIs with antidepressants may dangerously increase the risk of serotonin syndrome.

Though less severe, some other medications may interact with both Lexapro and Cymbalta, such as:

• Antiplatelets or anticoagulants, such as Jantoven (warfarin) or aspirin, may result in an increased risk of bleeding.
• Other medication classes that increase serotonin because these can increase the risk of serotonin syndrome. Examples include triptans such as Imitrex (sumatriptan), tricyclic antidepressants like amitriptyline, and certain opioids, such as methadone.
  

Some additional medications interact with Cymbalta but not Lexapro. Examples include:

• Medications that inhibit (block) certain liver enzymes, such as Cipro (ciprofloxacin), Tagamet (cimetidine), and Luvox (fluvoxamine). These interactions may lower Cymbalta's effectiveness.
• Antacids like calcium carbonate or Maalox. These prevent the body from absorbing Cymbalta effectively and potentially lower its effectiveness.

This is not a complete list of medications that may interact with Cymbalta or Lexapro. Before combining medications, check with a healthcare professional or pharmacist.

Choosing Between Cymbalta and Lexapro

Several factors are important to consider when deciding between Cymbalta and Lexapro.

Though both are similarly effective for treating depression in some people, others may not find the same success. If one of these drugs does not offer improvement, trying the other medication may work.

Another important consideration is side effects. Some studies suggest that Lexapro provides effective treatment with more tolerable side effects. Therefore, considering potential side effects is essential when selecting one of these medications.

Talking with a healthcare provider will work best when selecting one of these medications. This professional will understand your health background and what key factors they should address to ensure safe and effective care with either Cymbalta or Lexapro.

Summary

Lexapro and Cymbalta are two antidepressants commonly taken to manage depression and anxiety. Lexapro belongs to the SSRI drug class, while Cymbalta is part of the SNRI class of medications.

Clinical trials suggest these medications are similarly effective, but individual responses may vary. 

Though both drugs may commonly cause side effects like nausea and sexual dysfunction, Cymbalta tends to have more side effects compared to Lexapro. Both medications can interact with various medications, but Cymbalta's interactions may more significantly interfere with its effectiveness. 

When choosing between the two medications, your healthcare provider should consider factors such as individual response, side effect profiles, and interactions.