Does Cymbalta cause serotonin syndrome? (+3 factors)

 In this article, we will discuss whether Cymbalta causes serotonin syndrome. We will explore research studies on the incidence of serotonin syndrome with Cymbalta, as well as factors that may increase the risk of serotonin syndrome. Additionally, we will consider alternatives to Cymbalta in the event that it causes serotonin syndrome.

Does Cymbalta cause serotonin syndrome?

Yes, Cymbalta can cause serotonin syndrome. Although it is not a frequently reported side effect of this medication, the occurrence of serotonin syndrome with Cymbalta may be increased in the presence of certain risk factors, such as higher dosages or concurrent use of medications that increase serotonin levels, like fluoxetine or citalopram.

Cymbalta, an antidepressant commonly used for conditions such as depression and fibromyalgia, acts by influencing the levels of norepinephrine and serotonin. While the elevation of these neurotransmitter levels helps alleviate symptoms of various mental disorders, an excessively high concentration of serotonin may lead to serotonin syndrome in susceptible individuals (1).

What does research suggest?

According to research, Cymbalta can potentially cause serotonin syndrome in some patients. In a research study where Cymbalta was administered to treat underlying depression in individuals, the results showed that Cymbalta was effective in the management of depression. However, it was noted that 9% of the patients developed serotonin syndrome (3).

Another research study reported a case where an elderly patient with underlying depression was switched from Zoloft to Cymbalta. After using Cymbalta for one month, the patient started experiencing tremors, confusion, agitation, sweating, and nausea. Upon examination, healthcare providers diagnosed serotonin syndrome associated with the use of Cymbalta (2).

What are the symptoms of serotonin syndrome?

Serotonin syndrome is characterized by various symptoms, including (1):

  • increased heart rate
  • sweating
  • hallucinations
  • aggression
  • confusion
  • irritability
  • headache
  • hypertension 
  • vomiting
  • agitation
  • dizziness
  • coma 

It is important to note that while these symptoms are reported to be associated with serotonin syndrome, it is not necessary that all of them will occur in an individual. Most patients may report mild to moderate symptoms of serotonin syndrome; however, in rare cases, it can lead to coma or even death.

What factors can influence Cymbalta-induced serotonin syndrome? 

Several factors may increase the risk of serotonin syndrome with Cymbalta. In the presence of these factors, patients are more susceptible to experiencing serotonin syndrome. These factors include:

Higher dosage: A higher dosage of Cymbalta is more likely to cause serious side effects, including serotonin syndrome, compared to lower dosages. Higher dosages may lead to drug toxicity, and increased serotonin levels can contribute to the development of serotonin syndrome.

Use of other antidepressants: Concurrent use of other antidepressant medications with Cymbalta, especially those likely to increase serotonin levels in the brain, such as selective serotonin reuptake inhibitors (SSRIs) like Celexa and Prozac, raises the risk of developing serotonin syndrome. The combination of these medications should be approached cautiously.

Underlying neurological disorders: Individuals with certain underlying neurological disorders are more susceptible to serotonin syndrome. Liver Diseases Presence of liver diseases that affect the metabolism of Cymbalta can also increase the risk of serious side effects, including serotonin syndrome.

What to do if Cymbalta causes serotonin syndrome? 

If you experience any unusual symptoms while taking Cymbalta or suspect the occurrence of serotonin syndrome, you should consult your healthcare provider as soon as possible.

Initially, symptoms of serotonin syndrome may resemble the usual side effects of Cymbalta, such as fatigue, tiredness, nausea, and palpitations. However, if left undiagnosed, it can lead to serious consequences, including cardiovascular complications, hallucinations, coma, and, ultimately, death.

It is crucial to discuss your symptoms and the medications you are taking with your healthcare provider. They will assess your symptoms and determine the actual cause. If your symptoms are related to serotonin syndrome caused by Cymbalta, your healthcare provider may recommend dosage adjustments or discontinuation of the medication based on the severity of your symptoms.

However, the decision to discontinue Cymbalta should only be made by your healthcare provider. You should not change or stop your medication without consulting your doctor, as it may worsen your condition.

Serotonin syndrome may also be caused or exacerbated by the sudden discontinuation of Cymbalta.

What are the alternatives to Cymbalta if it causes serotonin syndrome? 

Alternatives to Cymbalta can be prescribed in cases where serious adverse effects, including serotonin syndrome, occur in individuals. However, it is important to note that all antidepressants that work by interfering with the levels of serotonin can potentially cause serotonin syndrome.

The risk is more common with medications that belong to the class of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. Antidepressant medications with a lower risk of serotonin syndrome, compared to Cymbalta, may include (4):

  • bupropion
  • desipramine 
  • amitriptyline 
  • mirtazapine
  • nortriptyline 

It’s essential to acknowledge that while these medications might have a lower risk of serotonin syndrome, they can cause other side effects that should be considered before starting any medication. The choice of suitable medication for an individual’s needs should be selected by considering the individual’s condition and overall health.

In my opinion, Cymbalta, like other antidepressants, may cause serotonin syndrome, but it occurs only in rare cases and typically in the presence of specific risk factors. If these risk factors are addressed first, the likelihood of experiencing symptoms of serotonin syndrome is reduced.

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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:


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Isbister GK, Polanski R, Cooper JM, Keegan M, Isoardi KZ. Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications. Clin Toxicol (Phila). 2022  ;60(9):1019-1023. doi: 10.1080/15563650.2022.2083631. Epub 2022 Jun 6. PMID: 35658766.


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