The Side Effects Of Duloxetine (Cymbalta)

Duloxetine (Cymbalta) belongs to the Selrotonine and Norepinephrine Reuptake Inhibitors (SNRIs) category of drugs. It is approved by the FDA for treating major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and diabetic peripheral neuropathy. (1)

Duloxetine raises dopamine levels in the prefrontal cortex, the foremost part of the brain. Because the prefrontal cortex is involved in the development of depression, Duloxetine’s actions in this region also contribute to its efficacy in treating depression.

The behavior of human beings has always been a topic of great interest for all researchers. The reason is its varying patterns and alterations that uniquely differ from person to person. It is almost amazing to see how the very same individual could exhibit different patterns of behavior over time.

For behavioral and mood-related disorders, it is best that a psychiatrist is consulted before any prescription medications are started. This is because medications used for mental disorders need constant monitoring for effective results and the development of adverse reactions.

Given below is an overview of the side effects of Duloxetine (Cymbalta).

Duloxetine – What Does It Do?

Duloxetine is linked with dopamine levels in the brain, particularly in the prefrontal cortex. Since the prefrontal cortex is seen to be associated with the development of depression, it acts on this center and increases the levels of dopamine in the brain. (2)

Duloxetine also increases the levels of serotonin and norepinephrine in between neurons. This effect may improve the symptoms of anxiety and depression in individuals.

Duloxetine can treat various chronic pain states by increasing the effect of neurons in the dorsal aspect of the spinal cord. A special set of neurons called “descending neurons” inhibit other types of neurons involved in pain processing. This suppresses excessive pain input from reaching the brain. The hypothesis is that a lack of inhibitory signals causes excessive input to the brain, which is perceived as pain.

Side Effects Of Duloxetine

Like every other drug, Duloxetine has possible adverse effects, which are worth knowing.

Some of the serious side effects linked to Duloxetine are given below:

Suicidal Ideation

This is a rare symptom but is seen to manifest in some patients who take Duloxetine. In clinical studies, it was seen that these patients developed suicidal thinking or behavior despite taking antipsychotic medications.

As with other antidepressants, researchers find it difficult to determine if suicidal ideation is due to the underlying mental condition or due to the effects of the medication (3). However rare, doctors constantly monitor for the appearance of symptoms of suicidal ideation in patients taking Duloxetine or other antidepressants.

Serotonin Syndrome

Although not that common, Duloxetine is seen to be linked with the development of a condition called Serotonin Syndrome.

Serotonin syndrome can occur in patients taking Duloxetine alone or in combination with other drugs known to cause the syndrome. (4)

Due to the increased levels of serotonin, patients may experience symptoms like excessive sweating, shivering, fever, confusion or coma (loss of consciousness), diarrhea, dilated pupils, or abnormal body movements. (5) Symptoms can vary in intensity.

If symptoms of serotonin syndrome appear, it is recommended that patients stop taking the medication and seek medical attention in the emergency room promptly.

Serotonin syndrome can occur when the dose of Duloxetine is increased or when the person begins taking a new prescription drug known to cause serotonin syndrome. Combining drugs containing serotonin, such as a migraine medication and an antidepressant, is the most common cause.

Syndrome Of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Another side effect related to the intake of Duloxetine is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In this condition, there is an excessive production or release of the antidiuretic hormone (ADH) in the affected people. (6)

When this occurs, the kidneys increase the retention of water, resulting in decreased sodium levels and an expanded cell volume. This syndrome can be severe in some people because it can disrupt their normal organ functioning.

Symptoms of SIADH include decreased volume of urine, weakness, easy exhaustion, weakness, trembling limbs, and seizures. As for serotonin syndrome, it is recommended that people experiencing symptoms of SIADH seek immediate medical attention.


Although uncommon, Duloxetine was also seen to cause or trigger manic episodes. It was seen that in patients who developed manic episodes, the amount of Duloxetine taken was up to 30 mg (7). This can happen in people with known or unknown bipolar disorder.

A manic episode consists of feeling invincible, highly energized, or euphoric. People with manic episodes usually have less need for sleep and can be more talkative than usual.

Doctors can check for symptoms of bipolar disorder when prescribing Duloxetine or other antidepressants. Therefore, it is recommended to attend every check-up appointment as directed by the practitioner.

Other Common Side Effects Of Duloxetine (Cymbalta):

Other side effects related to the usage of Duloxetine are as follows (8-9):

  • Nausea;
  • Headache;
  • Dry mouth;
  • Fatigue;
  • Sleepiness;
  • Difficulty falling asleep;
  • Dizziness;
  • Passing out;
  • Decreased appetite;
  • Blurred vision;
  • Nausea;
  • Constipation;
  • Diarrhea.

The most common adverse effects are usually mild and tend to subside on their own. (10) However, people taking Duloxetine should keep in constant communication with their doctor to report side effects for safe treatment.

Final Remarks

In case you are starting on your prescription of Duloxetine, it is highly essential that you monitor yourself for any changes or suspicious symptoms. In case there is any severe symptom, you should immediately report to the nearest ER. Your doctor can guide you on the best approach to address side effects.

Apart from side effects, Duloxetine is a beneficial drug and has helped many people with behavioral and mood disorders lead peaceful lives.


1. For what conditions is Duloxetine prescribed?

Duloxetine is an antipsychotic drug that is prescribed for several disorders, including major depressive disorder, generalized anxiety disorder, fibromyalgia, chemotherapy-induced peripheral neuropathy, and stress urinary incontinence.

2. Does Duloxetine have any side effects on one’s mood too?
Although not that common, Duloxetine was seen to affect some people’s moods, making them more agitated and irritable.

3. How to take my prescribed dose of Duloxetine?
Duloxetine was found to be effective when taken both before and after consuming a meal (11). There is no evidence that taking Duloxetine with meals affects the absorption or effect of Duloxetine.

4. What are the most common side effects of Duloxetine?
Nausea, diarrhea, and headaches are among the most common side effects of Duloxetine.

5. Who should not take Duloxetine?
Although considered safe, Duloxetine is contraindicated in patients with uncontrolled mania or bipolar disorder. Further, people with uncontrolled angle closure glaucoma are also asked to avoid taking this drug. (12)

See Also

What Are The Possible Side Effects Of Paxlovid?

Gabapentin Side Effects: Common and Severe Side Effects of Gabapentin

The Side Effects of Fluoxetine

Side Effects of Abilify

Trazodone Side Effects | Possible Side Effects of Trazodone

Current Version
August 11, 2023
Written By
Andleeb Asghar, PharmD
August 15, 2023
Medically Reviewed By
Franco Cuevas, MD
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  2. Duloxetine. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012 [cited 2023 Jun 28]. Available from: 
  3. Prakash A, Lobo E, Kratochvil CJ, Tamura RN, Pangallo BA, Bullok KE, et al. An Open-Label Safety and Pharmacokinetics Study of Duloxetine in Pediatric Patients with Major Depression. Journal of Child and Adolescent Psychopharmacology. 2012 Feb;22(1):48–55. 
  4. Gelener P, Gorgulu U, Kutlu G, Ucler S, Inan LE. Serotonin syndrome due to duloxetine. Clin Neuropharmacol. 2011;34(3):127–8. Serotonin syndrome due to duloxetine – PubMed (
  5. Hansbauer M, Strauss C. Severe serotonin syndrome under duloxetine in a patient with coeliac disease — Is there a connection? A case report. Eur J Psychiatry. 2021 Jul 1;35(3):193–6. Severe serotonin syndrome under duloxetine in a patient with coeliac disease — Is there a connection?
  6. Yang SJ, Wu PL. Severe hyponatremia and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) induced by duloxetine. Tzu Chi Med J. 2012 Mar 1;24(1):22–3. Severe hyponatremia and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) induced by duloxetine.
  7. Izci F, Zincir SB, Acar G, Ergun F, Semiz UB. Tek doz 30 mg duloksetin uygulamasını takiben ilk manik epizod. Dusunen Adam J Psychiatry Neurol Sci. 2014 Jun 15;178–80. Tek doz 30 mg duloksetin uygulamasını takiben ilk manik epizod.
  8. Wernicke, Joachim F., et al. “Safety and adverse event profile of duloxetine.” Expert opinion on drug safety 4.6 (2005): 987-993. Safety and adverse event profile of duloxetine.
  9. FDA drug label. Duloxetine (Cymbalta). [Accessed on 8/14/23]. Available from:  *Cymbalta (duloxetine hydrochloride) capsules (
  10. Bitter I, Filipovits D, Czobor P. Adverse reactions to duloxetine in depression. Expert Opin Drug Saf. 2011 Nov;10(6):839–50. Adverse reactions to duloxetine in depression – PubMed (
  11. Rizea‐Savu, Simona, et al. “The Effect of Food on the Single‐Dose Bioavailability and Tolerability of the Highest Marketed Strength of Duloxetine.” Clinical Pharmacology in Drug Development 9.7 (2020): 797-804. The Effect of Food on the Single‐Dose Bioavailability and Tolerability of the Highest Marketed Strength of Duloxetine.
  12. Drug Class Overview | Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) [Internet]. [cited 2023 Aug 11]. Available from: Drug Class Overview | Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

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