Cymbalta vs. Zoloft: Differences and Similarities

Cymbalta and Zoloft are antidepressant medications that are used for the treatment of major depressive disorder and other mental health conditions. Both medications are similarly effective for treating depression symptoms, but they have some differences in dosage and side effects.

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An estimated 17 million adults in the United States experienced a depressive episode in the last year.

Depressive episodes can severely affect a person’s quality of life. 

Treatment with antidepressant medications like Cymbalta and Zoloft can help those with major depressive disorder and other mental health conditions by balancing certain neurotransmitters in the brain to improve and stabilize mood.

These medications are particularly effective when combined with talk therapy and lifestyle changes. 

When considering which medication might be right for you, it is helpful to know the differences and similarities between Cymbalta vs. Zoloft.

Drug Class

Zoloft and Cymbalta belong to two different drug classes. 

Zoloft belongs to a class of prescription drugs called selective serotonin reuptake inhibitors (SSRIs), while Cymbalta belongs to a class of prescription drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs). 

SSRIs and SNRIs represent relatively new classes of prescription antidepressants; the first SSRI, Prozac, was approved by the U.S. Food and Drug Administration (FDA) in 1987, while the first SNRI, Effexor, was introduced in 1993.

SSRIs and SNRIs are associated with a lower risk of intolerable side effects than older classes of antidepressants, so patients are more likely to continue treatment with their medication. 

Both SSRIs and SNRIs work by inhibiting the reuptake of neurotransmitters in the brain that are known to affect mood, including serotonin.

Inhibiting the reuptake of the neurotransmitters increases the levels of these chemicals in the brain, which can improve and stabilize mood. 

Other SSRIs include citalopram (Celexa), paroxetine (Seroxat), escitalopram (Lexapro), and fluoxetine (Prozac or Oxactin).

Other SNRIs include venlafaxine (Effexor) and desvenlafaxine (Pristiq).

Conditions Treated

Cymbalta, sold under the generic name duloxetine, and Zoloft, sold under the generic name sertraline, are both used for the treatment of major depressive disorder.

Zoloft and Cymbalta should only be used to treat major depressive disorder in adults. However, Zoloft has other indications in which it can be used to treat children as young as six years old.

There are also other conditions treated by each medication that do not overlap.

Major Depressive Disorder

Major depressive disorder, sometimes referred to as MDD or clinical depression, is a mental health condition characterized by persistent, intense feelings of sadness that last for at least two weeks.

The condition is known to cause a number of different mental, physical, and emotional symptoms that can significantly affect a person’s quality of life. 

Symptoms of major depressive disorder include:

  • Feeling sad, empty, or tearful
  • Low energy levels
  • Sleeping and eating more or less than usual
  • Feelings of worthlessness, guilt, hopelessness, or helplessness
  • Difficulty concentrating
  • Lost of interest in activities that were previously enjoyed
  • Suicidal thoughts or behaviors

Other Conditions Treated by Cymbalta

In addition to major depressive disorder, Cymbalta is also used for the treatment of generalized anxiety disorder, fibromyalgia, and diabetic neuropathy.  

Generalized anxiety disorder, or GAD, is a type of anxiety disorder that causes persistent, intense feelings of anxiety that occur for at least six months or more and disrupt a person’s daily quality of life.

Symptoms include difficulty falling asleep, restlessness, sweating, nervousness, nausea, and trouble concentrating. 

Fibromyalgia is a type of chronic musculoskeletal pain that occurs throughout the body with no obvious cause.

Symptoms may include fatigue, depression, sleep issues, mood changes, tension headaches, and memory problems. 

Diabetic neuropathy is a type of nerve pain that can develop when high blood sugar levels remain uncontrolled.

Symptoms associated with diabetic neuropathy include nerve pain, tingling and numbness in the legs and feet, and increased sensitivity to touch. 

Other Conditions Treated by Zoloft

In addition to treating major depressive disorder, Zoloft is also used for the treatment of obsessive compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD).

Obsessive-compulsive disorder is a mental health condition characterized by persistent, worrisome thoughts (obsessions) and repeated behaviors that attempt to relieve the anxiety caused by the thoughts (compulsions). 

Symptoms of obsessive-compulsive disorder may include:

Panic disorder is a type of anxiety disorder in which a person experiences severe episodes of intense fear that manifest as panic attacks.

Panic attacks can cause physical symptoms like chest pain, dizziness, shortness of breath, heart palpitations, sweating,  and nausea.

Post-traumatic stress disorder (PTSD) is a mental health condition that affects some people after they experience a traumatic or terrifying event.

The condition is marked by symptoms like intense flashbacks, nightmares, anxiety, heightened reactions to triggers that remind the patient of the traumatic event, and a depressed mood.

Social anxiety disorder is a type of anxiety disorder in which patients feel overwhelming anxiety, fear, embarrassment, and self-consciousness during any type of social interaction.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS) that is characterized by symptoms of depression, irritability, and tension in the days before a woman’s menstrual period. 


Some studies have been conducted that compare Zoloft and Cymbalta in terms of their effectiveness in treating the symptoms of major depressive disorder and their tolerability in terms of side effects. 

In general, these studies have found that Zoloft and Cymbalta are similarly effective in the treatment of major depressive disorder.

The study found that depression severity and symptoms were similarly reduced by both medications, but Zoloft is more likely to reduce different symptoms of depression than Cymbalta.  

According to the study, Zoloft is more likely to reduce agitation, anxiety, and hypochondriasis, while Cymbalta has been shown to be more likely to reduce psychomotor retardation, general somatic symptoms, and sexual dysfunction.

Side Effects

Zoloft and Cymbalta are both associated with side effects.

Like many antidepressants, Zoloft and Cymbalta can cause side effects that may cause a person to discontinue the medication. 


Children and adults may experience the side effects of Zoloft differently.

There are some side effects known to occur in both adults and children, including: 

  • Nausea
  • Diarrhea
  • Loss of appetite
  • Indigestion 
  • Changes in sleep habits
  • Increased sweating
  • Sexual problems, including reduced sex drive and ejaculation failure
  • Shaking or tremors
  • Fatigue and drowsiness 
  • Agitation

Additional side effects associated with the use of Zoloft in children include:

  • Frequent urination
  • Aggressiveness
  • Abnormal increase in muscle movement or agitation
  • Nose bleeds
  • Heavy menstrual periods
  • Slowed growth rate 
  • Weight gain or weight loss

Serious side effects and their symptoms associated with Zoloft require immediate medical attention. Serious side effects of Zoloft include the following:

  • Suicidal thoughts and behaviors
  • Serotonin syndrome. This condition can be life-threatening. Symptoms can include:
    • Hallucinations
    • Fast heart rate
    • Sweating
    • Nausea
    • Vomiting
    • Changes in blood pressure such as high blood pressure
    • Muscle tremor or stiff muscles
    • Sweating
    • Diarrhea
    • Seizures
    • Dizziness
    • Shakiness
  • Severe allergic reactions with signs and symptoms such as:
    • Swelling of the face, tongue, eyes, or mouth
    • Trouble breathing
    • Severe rash
  • Seizures 
  • Abnormal bleeding
  • Manic episodes — symptoms can include:
    • Racing thoughts
    • Reckless behavior
    • Greatly increased energy
    • Severe trouble sleeping
    • Excessive happiness or irritability
    • Unusually grand ideas
    • Talking more or faster than usual
  • Changes in appetite or weight
  • Low sodium levels with signs and symptoms such as:
    • Headache
    • Confusion
    • Weakness or unsteadiness
  • Glaucoma

Seek medical advice from your healthcare provider if you experience any of these side effects or worsening side effects. This may not be a complete list of side effects.

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Common side effects associated with Cymbalta include:

  • Decreased appetite
  • Increased sweating
  • Vomiting
  • Diarrhea
  • Nausea
  • Dry mouth
  • Drowsiness
  • Constipation

Less common adverse effects that may occur while using Cymbalta include:

  • Stevens-Johnson syndrome
  • Manic/hypomanic episodes
  • Glaucoma
  • Seizures
  • Increased blood pressure
  • Low sodium levels
  • Liver problems
  • Orthostatic hypotension
  • Serotonin syndrome
  • Abnormal bleeding

This may not be a complete list of side effects, warnings, or precautions. You may also suffer from withdrawal symptoms if you stop the use of either medication without the help of a medical professional.


Zoloft and Cymbalta have been found to be similarly effective in treating medical conditions including major depressive disorder in adults according to several studies. 

Zoloft may be more likely to reduce symptoms of major depressive disorder that include agitation, anxiety, and hypochondriasis, while Cymbalta may be more likely to reduce psychomotor retardation, general somatic symptoms, and sexual dysfunction. 

Both medications can cause similar side effects, and some people may respond better to one medication than the other. Both medications are available in both generic and brand name forms by prescription only. 

Using a pharmacy discount card from can help you save money on your prescription regardless of whether your doctor believes Cymbalta or Zoloft is the best choice for your treatment.


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