Does Duloxetine increase serotonin? (3+ signs)

In this article, we will answer the question “Does Duloxetine increase serotonin?”. We will discuss the mechanism of duloxetine, research findings in this regard, some common signs of increased serotonin, factors affecting Duloxetine-induced serotonin levels, other medications that can increase serotonin levels, side effects of Duloxetine and when to consult your healthcare provider regarding any problems you are facing.

Does Duloxetine increase serotonin?

Yes, Duloxetine can increase the serotonin levels within the brain. Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) which acts by inhibiting the reuptake of serotonin and norepinephrine in the brain. This mechanism increases the levels of both neurotransmitters within the brain.

Duloxetine is an antidepressant belonging to the class of SNRIs and is approved by the FDA for the treatment of depressive illnesses, fibromyalgia, chronic musculoskeletal pain and diabetic peripheral neuropathic pain (DPNP) (1).

Serotonin is a neurotransmitter and a hormone responsible for the regulation of mood, cognition and memory. It affects many other functions in the body as well. Serotonin has a role in sleep, hunger, sexual health, stress and depression.

How does Duloxetine work?

Duloxetine inhibits the reuptake of serotonin and norepinephrine in the brain. It also increases the levels of dopamine in the prefrontal cortex due to the inhibition of norepinephrine transporters. It increases the activity of noradrenergic and serotonergic neurons (2). 

Due to these mechanisms, Duloxetine treats depression, anxiety, and neuropathic and musculoskeletal pain.

Keep in mind that Duloxetine may not be as effective in some patients due to individual characteristics, physiological factors and varied responses to the medication.

What does research suggest?

Many research studies have been published, that support the fact that Duloxetine increases serotonin levels in the brain.

A research study assessing the pharmacokinetics and pharmacology of Duloxetine stated this medication is a selective serotonin and norepinephrine reuptake inhibitor used in the treatment of depressive illnesses and neuropathic pain (3).

Another double-blind study of Duloxetine reported that the levels of serotonin and norepinephrine neurotransmitters were increased in healthy adults who were given this medication. Duloxetine inhibits the transporter cells of serotonin and norepinephrine thereby increasing the levels of these neurotransmitters (4).

One study, reported the clinical evidence of serotonin and norepinephrine reuptake inhibition by Duloxetine. This study stated that agents like Duloxetine which are dual-acting, have a broader spectrum of action and a greater efficacy when used in conditions like major depressive disorder (MDD) (5).

What are common signs of increased serotonin?

Some common signs of increased serotonin include the following signs and symptoms:

  • Increased mood
  • Increased energy
  • Improved appetite
  • Improved sleep
  • Gastrointestinal changes and disturbances
  • Serotonin syndrome

What factors affect Duloxetine-induced increase in serotonin levels?

Some factors that can affect Duloxetine-induced serotonin levels. They are as follows:

Patient variation: Each patient is different from the other. While some patients may respond positively, others may experience an extended range of side effects due to Cymbalta.

Dietary factors: Having a healthy diet is crucial to help with side effects that may occur as a result of Cymbalta therapy.

Lifestyle factors: Keeping a good balance between a healthy lifestyle and good physical activity can help increase the efficacy of Cymbalta.

Medications: Concurrent use of medications that affect serotonin levels can cause serotonin syndrome.

What other medications can increase serotonin levels?

Other medications that can alter levels of serotonin are as follows:

  • SSRIs like citalopram and escitalopram
  • Other SNRIs like desvenlafaxine and venlafaxine 
  • TCAs like amitriptyline and nortriptyline
  • MAOIs like selegiline and isocarboxazid
  • 5-HT receptor agonists like sumatriptan and rizatriptan

What are the possible side effects of Duloxetine?

Some possible side effects of Duloxetine are as follows:

  • Nausea
  • Dry mouth
  • Somnolence
  • Fatigue
  • Increased sweating
  • Decreased appetite and weight loss
  • Constipation
  • Diarrhoea
  • Suicidal thoughts and ideation
  • Serotonin syndrome
  • Orthostatic hypotension
  • Abnormal bleeding
  • Hyponatremia
  • Seizures
  • Urinary retention

When to consult your healthcare provider?

You should consult your healthcare provider if you are taking Cymbalta and are experiencing unwanted side effects like restlessness, hallucinations, diarrhoea, rapid heart rate, agitation or loss of coordination.

If you are experiencing these symptoms you should monitor and keep a record. Your healthcare provider should know about anything and everything you experience so he can evaluate your situation and give you another medication.

Sometimes your healthcare provider may decrease the dosage of Cymbalta to address any occurring side effects. You should always follow the instructions of your healthcare provider. Do not alter or change your medications without proper guidance from your doctor.

To the best of my knowledge, Cymbalta does affect serotonin levels within the brain and increases the activity of this neurotransmitter. If increased more than the required quantity this can lead to the appearance of serotonin syndrome.

In my opinion, if you are taking any medication which can alter the levels of serotonin or norepinephrine, you should extensively monitor your symptoms and look out for any new side effects.

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The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. CYMBALTA® (duloxetine hydrochloride) Delayed released capsules for oral use. Available from: 


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


Westanmo AD, Gayken J, Haight R. Duloxetine: a balanced and selective norepinephrine-and serotonin-reuptake inhibitor. American journal of health-system pharmacy. 2005 Dec 1;62(23):2481-90.


Chalon SA, Granier LA, Vandenhende FR, Bieck PR, Bymaster FP, Joliat MJ, Hirth C, Potter WZ. Duloxetine increases serotonin and norepinephrine availability in healthy subjects: a double-blind, controlled study. Neuropsychopharmacology. 2003 Sep;28(9):1685-93.


Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ. Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. International clinical psychopharmacology. 2008 May 1;23(3):161-9.

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