Does Trazodone interact with Cymbalta? (3+ precaution)

In this article, we will discuss the interaction between Trazodone and Cymbalta. We will also discuss the research studies on the use of Trazodone and Cymbalta together. Additionally, we will talk about the side effects associated with the use of this combination and how to use Trazodone and Cymbalta safely and effectively. 

Does Trazodone interact with Cymbalta? 

Yes, Trazodone can interact with Cymbalta. Trazodone and Cymbalta are the antidepressants which act by increasing the levels of serotonin in the body. A high dose of this drug combination can cause serotonin syndrome. (1,2)

Serotonin syndrome is a life-threatening condition, and its symptoms can vary from mild (nausea, vomiting) to severe (seizures, high blood pressure, etc). (3) Trazodone is used in combination to treat insomnia caused by Cymbalta, and a high dose of Trazodone can cause an increase in the levels of serotonin.

If you notice any negative changes in your behaviour, altered mental status, tremors, seizures, nausea, vomiting, etc., consult your physician for proper management and do not stop taking the medication suddenly, as it can cause withdrawal symptoms. 

What does the research suggest? 

Serotonin syndrome was reported in a 59-year-old patient who was being treated with Trazodone 100 mg for insomnia and Cymbalta 60mg for depression. She underwent a liver biopsy procedure for hepatitis. After 10 minutes of the procedure, she developed abdominal and chest pain, following which she was administered fentanyl. (4)

After 5 minutes of receiving fentanyl, she became agitated and hypertensive. She was admitted to the intensive care unit for observation. When a thorough assessment was made, the physicians found a possible interaction between fentanyl, duloxetine and trazodone, which led to serotonin syndrome. (4)

What are the benefits of taking Trazodone with Cymbalta? 

Trazodone is an antidepressant which is used to treat depression, anxiety, insomnia and other sleep-related disorders. Cymbalta is also an antidepressant of class serotonin-norepinephrine reuptake inhibitor (SNRI), which helps treat symptoms of depression, anxiety, fibromyalgia and chronic pain. (1,2)

The use of Cymbalta is associated with the side effect of insomnia (reduced sleep), and Trazodone is prescribed to help manage insomnia associated with the use of Cymbalta. In addition to that, Trazodone can also help treat symptoms of depression and gives an additive effect in managing mood-related symptoms and anxiety. (1,2)

Taking this combination comes with a risk, as an increased dose of these antidepressants can put you at risk of serotonin syndrome. Hence, it is important to follow your healthcare provider’s instructions and take the medication as prescribed. If you want to stop taking the drug, make sure you consult your physician, as drugs like Trazodone and Cymbalta require careful tapering before discontinuation. 

What are the alternatives to Trazodone and Cymbalta? 

Suppose you are experiencing any unwanted changes after taking Trazodone and Cymbalta together, which is affecting your day-to-day activities. In that case, you can choose to switch to other antidepressants, such as: 

  • SSRIs: citalopram, escitalopram, fluoxetine, paroxetine, sertraline.
  • SNRIs: venlafaxine, milnacipran, desvenlafaxine, levomilnacipran
  • Tricyclic antidepressants: amitriptyline, amoxapine, nortriptyline, imipramine.
  • Atypical antidepressants: bupropion, mirtazapine. 
  • Monoamine oxidase inhibitors (MAOIs): isocarboxazid, selegiline. 

If you have been prescribed Trazodone to manage insomnia, you can choose other drugs which help treat insomnia, such as benzodiazepines (triazolam, estazolam, temazepam), Non-benzodiazepines (zolpidem, zaleplon), melatonin agonist (ramelteon), orexin receptor antagonist (suvorexant), antihistamine (diphenhydramine). 

How to use Trazodone and Cymbalta safely and effectively? 

There are a few measures to follow in order to use Trazodone and Cymbalta safely and effectively, such as

  • If you have been prescribed Cymbalta and Trazodone together, take Cymbalta in the morning and Trazodone in the evening. 
  • If you forgot to take a dose of the drug, take it as soon as you remember, only if the time gap between the next dose is more.
  • Do not take a double dose of the drug, as it can cause overdose and increase the risk of serotonin syndrome. 
  • Look out for any unwanted changes in your behaviour, as Trazodone can increase suicidal thoughts. 
  • Monitor for any unwanted side effects while consuming Trazodone and Cymbalta. 
  • Do not miss a dose or stop taking the drug suddenly, as it can cause withdrawal symptoms and worsen your condition. 
  • If you accidentally take Trazodone in the morning, don’t engage in any activities such as driving, handling heavy machinery, etc. 

In my opinion, as a pharmacist, taking Trazodone and Cymbalta together can be beneficial if you have antidepressant-induced insomnia. However, the dose of these drugs should be managed carefully in order to avoid serotonin syndrome. If you are experiencing any unwanted side effects, make sure you consult your physician. 

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Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. 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:  


Simon LV, Keenaghan M. Serotonin Syndrome. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: 

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