Does trazodone cause leg swelling? (3+ side effects)

In this article, we will talk about trazodone-induced leg swelling. We will discuss some research studies associated with leg swelling along with other factors that can contribute to leg swelling. 

Does trazodone cause leg swelling? 

Yes, trazodone can cause swelling in the leg. Trazodone-induced leg swelling is a rare side effect. The severity and occurrence vary among individuals. Trazodone is an antidepressant which helps treat symptoms of depression, insomnia associated with depression, and other sleep-related problems. (1)

In medical terms, leg swelling is also known as peripheral edema. It can occur due to several other reasons, such as kidney and liver damage, heart failure, allergies, venous insufficiency, and other drugs such as corticosteroids, prednisolone, etc. 

Hypersensitivity/allergy to trazodone can cause swelling and rashes in the body. If you are allergic to the drug, stop taking it and seek medical help immediately. 

If you are experiencing any unwanted effects after consuming trazodone, make sure you visit your physician for proper management and avoid abrupt discontinuation of the drug, as it can cause withdrawal symptoms and worsen your condition. 

What does the research suggest? 

J Barrnett et al. presented a case series about trazodone-associated peripheral oedema in ten patients treated with trazodone. These ten patients showed symptoms of leg swelling and weight gain, which subsided after discontinuation of the drug. The study also stated that the side effect was related to the dose of the drug. (2)

Another case report presented by Yang et al. of a 52-year-old female who was being treated with trazodone 50mg per day for her depression developed swelling in her leg, which, when examined, revealed as a grade 2+ pitting edema in both legs, following which trazodone was discontinued. The leg swelling subsided within 5 days after discontinuation of the drug. (3)

Research studies have reported that a dose higher than 150-600mg of trazodone can induce leg swelling. However, every individual responds to the drug differently, and the effects of the drug can vary among individuals. (3)

What factors contribute to leg swelling while taking trazodone? 

Several factors can contribute to leg swelling while taking trazodone, such as:  

  • Allergic reaction: If you are allergic to trazodone, you may develop swelling in your legs and face. 
  • Hyponatremia: Antidepressants can cause hyponatremia (low levels of sodium), which can cause fluid retention and contribute to swelling. 
  • Serotonin syndrome: An increased dose of trazodone or a combination of trazodone with other antidepressants can cause serotonin syndrome, which can cause swelling in the leg 
  • Underlying medical conditions: Conditions such as heart failure, kidney failure, and vascular insufficiency can cause edema (an abnormal accumulation of fluid) in the legs, feet, etc. 
  • Medications: Other medications, such as corticosteroids, prednisolone, NSAIDs, antihypertensives, etc, can contribute to leg swelling. 
  • Inactivity: Prolonged sitting or lying down can lead to the build-up of fluid in feet and ankles due to improper blood flow. 

What to do if you are experiencing trazodone-induced leg swelling? 

If you are experiencing leg swelling while consuming trazodone, the first thing you should do is consult your physician. Your physician will make the necessary changes to your treatment. Leg swelling can also be caused due to other underlying conditions. Get evaluated for any underlying condition that may be the cause of swelling in your leg. 

Before taking any OTC medication, consult your doctor, as some of the drugs can contribute to leg swelling. Do not discontinue taking your drug, as it can cause withdrawal symptoms and worsen your condition. Always consult a physician before altering the course of the treatment.

Take trazodone as prescribed by your doctors, and if you miss a dose, do not take a double dose, as it can cause an overdose. If the time gap between the next dose is long, take it as soon as you remember, or skip it and take the next one. Avoid taking trazodone in the morning, as it can cause sedation.

Make some lifestyle changes, such as eating a balanced and healthy diet and exercising regularly, as inactivity can lead to leg swelling. 

What are the alternatives if trazodone causes leg swelling? 

If you are experiencing any side effects after consuming trazodone, which is affecting day-to-day activities, you can choose to switch to safer alternatives such as: 

  • Selective serotonin inhibitors (SSRIs): citalopram, fluoxetine, paroxetine, and sertraline. 
  • Serotonin-norepinephrine inhibitors (SNRIs): venlafaxine, milnacipran, desvenlafaxine, levomilnacipran. 
  • Tricyclic antidepressants: amitriptyline, amoxapine, nortriptyline, imipramine. 
  • Atypical antidepressants: bupropion, mirtazapine.
  • Monoamine oxidase inhibitors: isocarboxazid, selegiline. 

If you have been prescribed trazodone to treat insomnia related to drug use or depression and you are experiencing side effects, you can choose to switch to other medication which helps treat insomnia, such as: (4)

  • Antidepressants: mirtazapine, amitriptyline, doxepin. 
  • Benzodiazepines: triazolam, esrazolam, temazepam, quazepam, flurazepam.
  • Melatonin agonist: ramelteon.
  • Orexin receptor antagonist: Suvorexant 
  • Atypical antipsychotics: quetiapine, olanzapine, risperidone. 
  • Antihistamines: diphenhydramine, doxylamine. 
  • Herbal supplements: valerian, kava. 

Any alteration to your treatment should be done under the guidance of a healthcare provider. Your physician will evaluate and adjust your treatment accordingly. 

In my experience as a pharmacist, trazodone can cause swelling in the legs. However, this side effect is rare and occurs in a few individuals. There are many other factors which can contribute to leg swelling. I recommend getting a proper check-up to rule out any underlying cause of leg swelling.


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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: 


Barrnett JO, Frances AL, Kocsis JA, Brown RI, Mann JJ. Peripheral edema associated with trazodone: a report of ten cases. Journal of Clinical Psychopharmacology. 1985 Jun 1;5(3):161-4. Available from: 


Yang HT, Liu YW, Kuo SC, Chen CY, Yeh YW. Repeated leg edema induced by trazodone and mirtazapine in a patient with depression with successful agomelatine substitution: a case report. American Journal of Therapeutics. 2022 Nov 1;29(6):e703-5. Available from: 


Lie JD, Tu KN, Shen DD, Wong BM. Pharmacological treatment of insomnia. Pharmacy and Therapeutics. 2015 Nov;40(11):759. Available from:  

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