Does Cymbalta work better than Zoloft? (3+ differences)

This article will explore whether Cymbalta works better than Zoloft. It will compare their therapeutic benefits, efficacies, mechanisms of action, and side effects.

Finally, the article will provide tips on how to choose between both medications.

Does Cymbalta work better than Zoloft?

Cymbalta may work better than Zoloft for certain conditions. These conditions include neuropathic pain in fibromyalgia, peripheral diabetic neuropathies, and osteoarthritis. However, for other conditions like PTSD, OCD, and bulimia nervosa, Zoloft may be more beneficial [1,2].

It’s important to note that people respond differently to medications, and Cymbalta may not work better than Zoloft for everyone. Therefore, consulting with a healthcare professional is crucial in determining the most suitable antidepressant for your specific needs.

They will assess your medical history, consider any comorbidities, concurrent medications, and responses, and prescribe the most appropriate drug accordingly.

How do Cymbalta and Zoloft differ from one another?

The differences between Zoloft and Cymbalta are mentioned below:

Mechanisms of action

Cymbalta primarily works by increasing both serotonin and norepinephrine in the brain by inhibiting their reuptake. This dual action on serotonin and norepinephrine differentiates it from many other antidepressants that increase serotonin alone [1].

In contrast, Zoloft is a selective serotonin reuptake inhibitor (SSRI) that primarily raises serotonin levels in the brain, which may improve mood [2].

Due to the differences in their mechanisms, there are differences in their effectiveness for specific diseases or conditions. For example, duloxetine’s action on norepinephrine makes it effective in treating neuropathic pain.

Due to Zoloft’s selective action on serotonin, it is mainly indicated for mental health disorders.

Therapeutic benefits 

The FDA-approved uses for Cymbalta and Zoloft are demonstrated below [1,2]:

Cymbalta Zoloft
Major depressive disorder Major depressive disorder
Generalized anxiety disorder Social anxiety disorder
Fibromyalgia Post-traumatic stress disorder 
Diabetic peripheral neuropathy Obsessive-compulsive disorder
Chronic musculoskeletal pain Premenstrual dysphoric disorder 
  Panic disorder 

Off-label uses of Zoloft include binge eating disorder, premature ejaculation, body dysmorphic disorder, generalized anxiety disorder, and bulimia nervosa. 

Duloxetine, on the other hand, can be used off-label to manage chemotherapy-related peripheral neuropathy and stress urinary incontinence.


When comparing the efficacy of Cymbalta and Zoloft for the treatment of depression and anxiety, there are some differences in the reported improvements in symptoms.

For depression symptoms, Cymbalta appears to show a higher percentage of improvement. In one month, Cymbalta demonstrated a 64% improvement, while Zoloft showed a 29% improvement. After two months, Cymbalta showed an 87% improvement, compared to a 66% improvement with Zoloft.

At three months, the improvement reported with Cymbalta was 86%, while Zoloft reported an 82% improvement [3].

For anxiety symptoms, at one month, Cymbalta showed a 33% improvement, whereas Zoloft demonstrated a 22% improvement. After two months, Cymbalta had a 47% improvement compared to a 21% improvement with Zoloft [3].

At three months, Cymbalta reported a 64% improvement, while Zoloft showed a 28% improvement. These percentages suggest that Cymbalta may provide slightly greater improvement in both depression and anxiety symptoms compared to Zoloft, based on the provided data [3].

However, it’s essential to remember that individual response and effectiveness can vary, and other factors such as side effects and tolerability should also be considered when choosing a medication. It is always best to consult with a healthcare professional for personalized advice and guidance.

Side effects

Here’s a comparison of the side effects caused by Cymbalta and Zoloft [1,2]:

Cymbalta  Zoloft
Vomiting Nausea
Insomnia Insomnia
Loss of appetite Loss of appetite
Vision problems Anxiety
Increased bleeding due to inhibition of platelet aggregation Increased bleeding due to inhibition of platelet aggregation
Sleepiness Dizziness
Weight gain Fatigue
Postural hypotension Postural hypotension
Weight loss  Syncope
Diarrhea Diarrhea
Liver problems, which may cause easy bruising and dark urine Photosensitivity
Tremors Tardive dyskinesia 

How to choose between Cymbalta and Zoloft?

When choosing between Cymbalta and Zoloft, it is important to consider several factors, including contraindications, indications, and individual responses to the medications.

Cymbalta is contraindicated in patients with uncontrolled narrow-angle glaucoma because it may increase intraocular pressure. Moreover, people with liver or kidney problems should avoid taking Cymbalta.

Zoloft, on the other hand, is contraindicated in patients taking sulfiram or pimozide. If, during the last 14 days, you have administered a monoamine oxidase inhibitor (MAOI), you should completely avoid both medications. 

Furthermore, for most people, Cymbalta is often preferred for the treatment of generalized anxiety disorder, fibromyalgia, diabetic peripheral neuropathic pain, and chronic musculoskeletal pain.

On the other hand, Zoloft is often preferred for the treatment of depression, social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and panic disorder.

However, it is crucial to consult with a doctor who can assess your needs and medical history before making a decision about which medication is more suitable. Only a doctor can determine which drug is more appropriate based on an individual’s unique circumstances.


Based on my knowledge, Cymbalta may be more effective than Zoloft in certain conditions, and vice versa. Moreover, while they share certain common side effects and contraindications, they also have certain different and specific ones.

Additionally, I believe that the decision regarding the use of either Cymbalta or Zoloft as antidepressants should depend on one’s medical and medication histories. In my perspective, only a doctor can determine which drug may work better for your condition.

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Dhaliwal JS, Spurling BC, Molla M. Duloxetine. [Updated 2023 May 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Singh HK, Saadabadi A. Sertraline. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Karaiskos D, Tzavellas E, Spengos K, Vassilopoulou S, Paparrigopoulos T. Duloxetine versus citalopram and sertraline in the treatment of poststroke depression, anxiety, and fatigue. J Neuropsychiatry Clin Neurosci. 2012 Summer;24(3):349-53. doi: 10.1176/appi.neuropsych.11110325. PMID: 23037649.

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