Can duloxetine cause depression? (+5 alternatives)

In this article, we will discuss whether duloxetine causes depression. We will also discuss the research studies investigating the association between duloxetine and depression. Additionally, we will explore the alternative to duloxetine, if it fails to manage depression.

Can duloxetine cause depression?

No, duloxetine does not cause depression. It may exacerbate a few symptoms of depression during the initial phase of treatment in patients with underlying depression, however, it does not induce depression in non-depressive patients. 

Duloxetine is an antidepressant medication that works by interfering with the concentration of serotonin and norepinephrine in the brain. The elevated levels of these neurotransmitters help in the regulation of mood and alleviation of various symptoms of depression, anxiety, and other medical conditions such as fibromyalgia and chronic pain (1).

Duloxetine is generally a well-tolerated medication but it may cause various side effects during the start of treatment when the body is adjusting to the medication. The most common side effects associated with its use may include nausea, vomiting, dizziness, headaches, and fatigue.

What does research suggest?

There is currently no research evidence indicating that duloxetine is the cause of inducing depression in non-depressive patients. However, some studies suggest that this medication may exacerbate a few symptoms of depression in certain individuals.

In a research study assessing the effectiveness of duloxetine in treating depression, it was found that less than 10% of patients discontinued the medication within a few weeks of treatment. The decision to stop was attributed to the exacerbation of symptoms of depression (2). 

In another research study involving patients less than 18 years of age, treated with duloxetine for depression, the results indicated both efficacy and safety. However, it was observed that 3% of the patients experienced an increase in suicidal tendencies, leading to a worsening of depressive symptoms (3).

What are the depression-related side effects of duloxetine?

Duloxetine is generally considered a safer medication, but it may exacerbate a few symptoms of depression in some individuals, based on their sensitivity to medication and overall health condition. These symptoms may include (1):

  • suicidal tendencies
  • changes in mood
  • behavioral changes 
  • mood swings
  • irritability 
  • aggression
  • agitation
  • confusion

It is important to note that these symptoms do not occur in all individuals who take this medication. The incidence of worsening of depression is low with this medication, however, you should consult your healthcare provider if you experience any unusual symptoms after using duloxetine.

What to do if duloxetine exacerbates the symptoms of depression?

If duloxetine fails to manage depression or worsens the symptoms associated with it, it is important to consult your healthcare provider. They can assess your condition and determine the actual cause of treatment failure. 

It is crucial to remain patient during the course of treatment, as duloxetine may take time to show its full therapeutic effects. In the initial stages, some individuals may experience an exacerbation of side effects, including a temporary worsening of depressive symptoms. However, with continued use, the medication often begins to alleviate depression and improve overall mood.

Individuals need to communicate openly with their healthcare providers about any concerns or changes in symptoms, allowing for adjustments to the treatment plan as needed.

If duloxetine is associated with worsening depression, your healthcare provider may recommend an alternative. However, you should not make any changes in the treatment plan involving duloxetine, including dosage adjustment or discontinuation of the medication, without consulting your healthcare provider. Sudden withdrawal of duloxetine without the consultation of a healthcare provider may lead to discontinuation syndrome.

What are the alternatives to duloxetine for managing depression?

Alternatives to duloxetine that can be effectively used for the management of depression and its associated symptoms, may include (4): 

  • other serotonin and norepinephrine reuptake inhibitors (venlafaxine) 
  • selective serotonin reuptake inhibitors (citalopram, fluoxetine)
  • tricyclic antidepressants (amitryptiline)
  • atypical antidepressants (bupropion)
  • tetracyclic antidepressants (mirtazapine)

These alternative medications can be effectively utilized for managing depression. While they differ in their mechanism of action, they are all indicated for the treatment of depression, offering a range of options to tailor the treatment to individual needs.

To my knowledge, duloxetine does not cause depression, instead, it is a drug of choice for managing depression. However, in some cases, it may worsen symptoms of depression in patients with pre-existing depression. It’s crucial to stay vigilant and consult your doctor if you experience any unusual symtoms after taking duloxetine.

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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:


Dunner DL, Wilson M, Fava M, Kornstein S, Munoz R, O’Reardon J, Trivedi M, Wohlreich M. Long-term tolerability and effectiveness of duloxetine in the treatment of major depressive disorder. Depress Anxiety. 2008;25(5):E1-8. doi: 10.1002/da.20339. PMID: 17621644.


Prakash A, Lobo E, Kratochvil CJ, Tamura RN, Pangallo BA, Bullok KE, Quinlan T, Emslie GJ, March JS. An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression. J Child Adolesc Psychopharmacol. 2012 Feb;22(1):48-55. doi: 10.1089/cap.2011.0072. Epub 2012 Jan 17. PMID: 22251023.


Sheffler ZM, Patel P, Abdijadid S. Antidepressants. [Updated 2023 May 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:

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