Zoloft vs. Cymbalta: Similarities, Differences, & Side Effects

By Nena Luster DNP, MBA, FNP-BC
Medically reviewed checkmarkMedically reviewed
February 25, 2022

Cymbalta (duloxetine) is an antidepressant medication that falls under the medication category of selective serotonin-norepinephrine reuptake inhibitors (SNRIs). 

Zoloft (sertraline) is also an antidepressant medication but is a selective serotonin reuptake inhibitor (SSRI), which functions differently from SNRIs. 

While both medications are widely popular for treating mental health conditions such as depression (major depressive disorder), they have similarities and differences. 

In this article, we’ll compare Zoloft and Cymbalta by going over the conditions they’re used to treat, cost differences, potential side effects, and what you need to know to take Zoloft or Cymbalta safely.

What Are the Similarities & Differences Between Zoloft and Cymbalta?

Both medications are used to treat a variety of symptoms and mental health conditions. One of the biggest differences between Zoloft and Cymbalta is the medication class they’re in. 

Selective serotonin reuptake inhibitors (SSRIs) such as Zoloft work to increase the amount of serotonin in the brain and body to improve mood, stress, sleep, and metabolism. 

Selective serotonin-norepinephrine reuptake inhibitors (SNRIs) such as Cymbalta work to increase the amount of norepinephrine and serotonin in the brain and body to improve mood, stress, and pain symptoms. 

Here are some other comparisons of Cymbalta and Zoloft.

ZoloftCymbalta
Medication classSelective serotonin reuptake inhibitor (SSRI)Selective norepinephrine reuptake inhibitor (SNRI)
Generic nameSertralineDuloxetine
Brand nameZoloftCymbalta
Administration formOral liquid or tabletOral capsule
Standard dosage50mg once a day60mg once a day 
Length of treatmentLong-term (maintenance treatment)Long-term (maintenance treatment)
Age range for treatmentAges 6+Ages 7+
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What Conditions Are Treated with Zoloft and Cymbalta?

Zoloft and Cymbalta both treat various neurological and psychological disorders. The table below compares the conditions each medication treats.

One important difference between Zoloft and Cymbalta is that Cymbalta, an SNRI, is sometimes used to treat nerve pain symptoms. 

Research is yet to discover the particular mechanism behind how Cymbalta helps with pain, and studies are still exploring how Cymbalta affects patients with osteoarthritis, fibromyalgia, and other neuropathic pain. 

Zoloft has been on the market longer, as it was approved by the Federal Drug Administration (FDA) in 1990. Cymbalta was approved in 2004. 

This means that Zoloft has had more time to be extensively tested for a variety of symptoms and disorders. It is also one of just four medications approved by the FDA to use for children with obsessive-compulsive disorder (OCD). 

ZoloftCymbalta
Major depressive disorder (MDD)YesYes
Generalized anxiety disorder (GAD)Yes (off label)Yes
Pain resulting from fibromyalgiaNoYes
Neuropathic painNoYes
Pain resulting from other musculoskeletal issuesNoYes
Urinary incontinenceNoYes
Social anxiety disorderYesNo
Obsessive-compulsive disorder (OCD)YesNo
Post-traumatic stress disorder (PTSD)YesNo
Panic disorderYesNo
Premenstrual dysphoric disorder (PMDD)YesNo

*  Off-label means it can be used for the condition but is not an official indication

Which Is More Effective, Zoloft or Cymbalta?

Each drug has been tested vigorously for a variety of health conditions and psychological disorders. Depending on which health concern you have, one may have more benefits over the other, and your healthcare provider will talk to you about which one may be best.

Some studies have directly compared Zoloft (sertraline) and Cymbalta (duloxetine) for patients with clinical depression. 

One study compared 63 patients who took either sertraline or duloxetine to treat Major Depressive Disorder (MDD). It found that the medications were overall similar for treatment efficacy, but each worked better for certain symptoms. 

Zoloft was more effective for symptoms relating to anxiety, agitation, and excessive fears of having an illness. But Cymbalta was more effective for treating physical symptoms slowed movement/thinking, and sexual problems.

Depending on your medical history, other current medications, and specific symptoms, either Zoloft or Cymbalta may be a better choice for you. Your healthcare provider will be able to work with you to determine which medication will be most effective for your needs.

Cost & Coverage of Zoloft vs. Cymbalta

Costs for prescriptions vary by state and city. The available insurance coverage for Zoloft and Cymbalta also differs depending on the area you live in.

Both Zoloft and Cymbalta are typically covered by commercial and Medicare/Medicaid healthcare plans, but costs can vary if you do not have prescription coverage or have to pay a copayment for prescriptions.

Like any other medication, the brand name is typically more costly than the generic brand.

The average cost for 30 days of brand-name 50mg Zoloft capsules is around $140. If you choose a generic brand of sertraline, a 30-day treatment may only cost $13.

The average cost for 30 days of brand-name 60mg Cymbalta capsules is around $350. If you choose a generic brand of duloxetine, a 30-day treatment is only around $20. 

What are the Side Effects of Zoloft and Cymbalta?

Zoloft and Cymbalta each have common side effects. See the table below for the most common side effects of each medication. This list does not include all of the possible side effects. 

If you are considering taking Zoloft or Cymbalta, be sure to ask your healthcare provider about any potential side effects.

ZoloftCymbalta
NauseaYes (common)Yes (common)
ConstipationYes (uncommon)Yes (common)
Dry mouthYes (common)Yes (common)
DiarrheaYes (common)Yes (common)
Abdominal painYes (uncommon)Yes (uncommon)
DizzinessYes (common)Yes (common)
LightheadednessNoYes (common)
FatigueYes (common)Yes (common)
HeadacheYes (common)Yes (common)
ConvulsionsNoYes (uncommon)
InsomniaYes (common)Yes (common)
Vivid dreamsNoYes (common)
AgitationYes (uncommon)Yes (common)
AnxietyNoYes (common)
Panic attacksNoYes (common)
RestlessnessYes (common)No
SweatingYes (common)No
Heart palpitationsNoYes (common)
High blood pressureNoYes (common)
Chest painNoYes (uncommon)
RashesYes (uncommon)No
Decreased sex driveYes (common)Yes (common)
Inability to orgasmYes (common)Yes (common)
Delayed ejaculationYes (common)Yes (common)
Erectile dysfunctionYes (common)Yes (common)
Painful urinationNoYes (uncommon)
Testicular painNoYes (uncommon)
Abnormal visionYes (uncommon)Yes (common)
Dry eyesNoYes (uncommon)
CoughNoYes (common)
Sore throatNoYes (common)

Zoloft and other SSRIs can also sometimes cause weight gain. While the mechanisms behind the weight gain is not fully understood by experts, it may have something to do with changes in metabolism or appetite.

There is also data that shows some patients experience weight loss when they initially start Cymbalta.

Talk to your healthcare provider before stopping any antidepressant. 

If you stop taking Zoloft, Cymbalta, or another antidepressant without slowly reducing your dosage, you might experience uncomfortable symptoms or even antidepressant discontinuation syndrome

Symptoms of this syndrome include nausea, vomiting, headaches, and other flu-like symptoms. To be safe, notify your healthcare provider if you begin to experience any of these symptoms.

You can take some over-the-counter medications to improve some symptoms, and they typically subside after a couple of weeks.

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Drug Interactions and Warnings

Starting a new antidepressant has the potential to increase the risk of suicidal thoughts and depressive symptoms. If you experience any suicidal thoughts or are considering suicide, go to the nearest medical facility for immediate care. 

You can also call the National Suicide Prevention Lifeline (Lifeline) at 1-800-273-TALK (8255), or text the Crisis Text Line (text HELLO to 741741). These services are free, confidential, and available 24/7.

Both SSRIs like Zoloft and SNRIs like Cymbalta are known to have negative interactions with the following treatments and medications:

  • Treatments for seizure disorders
  • Treatments for psychosis and schizophrenia
  • Antiplatelet medications
  • Lithium
  • Triptans for migraines
  • Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen
  • Tricyclic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)

Certain drug interactions can result in dangerous and even fatal consequences.

Be sure to discuss your medical history and current medications with your healthcare providerbefore beginning any new treatment or medication.

Pregnancy and Breastfeeding

If you become pregnant while taking Zoloft or Cymbalta, notify your healthcare provider immediately.

Some SSRIs and SNRIs can cause negative effects on pregnancy or cause birth defects. 

People who are breastfeeding should discuss their medication options with their healthcare provider. 

Many times SNRIs like Cymbalta are not recommended while breastfeeding, but some SSRIs like Zoloft are approved for use while breastfeeding. 

Serotonin Syndrome

Both Zoloft and Cymbalta affect serotonin levels in the brain and body.

If too much serotonin is present, serotonin syndrome may occur. Serotonin syndrome is more likely to happen when you take other medications that increase serotonin in the body.

Examples include taking multiple antidepressants at the same time or using supplements such as  St. John’s Wort. 

Serotonin syndrome is considered a medical emergency and you should seek immediate emergency care if you display the following symptoms:

  • Hallucinations
  • Uncontrolled muscle spasms
  • Unusual agitation or restlessness
  • Nausea and vomiting
  • Black, bloody stool
  • Fever
  • Rapid heart rate
  • Severe dizziness
  • Loss of coordination

How K Health Can Help

Choosing the right medications can be challenging, so it’s wise to discuss with a healthcare provider. Did you know you can get affordable primary care with the K Health app?

Download K to check your symptoms, explore conditions and treatments, and if needed text with a doctor in minutes. K Health’s AI-powered app is HIPAA compliant and based on 20 years of clinical data.

Frequently Asked Questions

Which is better for depression, Zoloft or Cymbalta?
When treating depression and depressive disorders, each medication has its specific benefits. Some studies have shown that Zoloft was more effective for symptoms relating to anxiety, agitation, and excessive fear of having an illness. But Cymbalta was more effective for treating physical symptoms, slowed movement/thinking, and sexual problems. The better medication option for the treatment of depression depends on the individual.
Can you switch from Zoloft to Cymbalta?
If you find that you are unhappy with the medication you’re currently taking, speak with your healthcare provider to learn about alternatives. Switching from an SNRI to an SSRI (or from an SSRI to an SNRI) must be carefully considered, as these drugs can interact with other medications and treatments.
What is stronger, Zoloft or Cymbalta?
Neither drug is stronger than the other, and they each have their own ways of affecting the brain and body. If you are looking to treat specific symptoms while experiencing clinical depression, one medication may be recommended over the other.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Nena Luster DNP, MBA, FNP-BC

Nena Luster is a board certified Family Nurse Practitioner with over 14 years of experience including emergency medicine, urgent care, and family practice.