Does trazodone change brain chemistry? (+ 3 effects)

In this article, we will discuss the impact of trazodone on brain chemistry. We will look at the therapeutic and common side effects of altered brain chemistry due to trazodone. 

Does trazodone change brain chemistry?

Yes, trazodone can change the brain chemistry. Trazodone tends to alter brain chemistry by altering levels of serotonin, histamine, and norepinephrine in the brain. 

Trazodone belongs to the serotonin antagonist and reuptake inhibitor antidepressant drug class. It also tends to block histamine and alpha-adrenergic receptors in the brain. 

Trazodone is an FDA-approved medication for the treatment of major depressive disorder. It is also used off-label for the treatment of anxiety, fibromyalgia, and substance abuse. 

Trazodone alters brain chemistry through its mechanism of action. It is generally considered a safe antidepressant but may not be effective in some patients and mess up with their brain chemicals causing severe side effects. 

How does trazodone change brain chemistry?

The following are the mechanisms by which trazodone alters brain chemistry (1): 

  • Serotonin antagonism- Trazodone does not contain serotonin in its composition rather it exerts its action on the brain by serotonin antagonism. It blocks certain serotonin receptors and by blocking these receptors, trazodone modulates the activity of serotonin in the brain. 


  • Serotonin reuptake inhibition- Trazodone also inhibits the reuptake of serotonin in the presynaptic nerve terminals. By inhibiting the reuptake of serotonin, trazodone allows more serotonin in the synaptic cleft, exerting more serotonergic effects. 


  • Alpha-adrenergic blockade- Trazodone also possesses alpha-adrenergic blocking properties. It blocks certain receptors for norepinephrine and other neurotransmitters as well which is not clearly understood. 


  • Histamine receptor blockade- Trazodone also tends to block the histamine receptors which may be the reason to exert sedative properties. 

What are the effects of trazodone-altered brain chemistry?

The following are some effects of altered brain chemistry due to trazodone:

Therapeutic effects

The change in brain chemistry due to alterations in the brain chemicals caused by trazodone leads to the following therapeutic effects in patients (1,2):

  • Antidepressant effects- Trazodone is an antidepressant medication and is primarily prescribed to alleviate symptoms of depression in patients. 


  • Anxiolytic effects- Similarly, trazodone also tends to reduce anxiolytic symptoms in patients due to alterations in serotonin levels in the brain. 


  • Sedation- Trazodone is prescribed as an off-label medication to treat insomnia due to sedative properties. It is also not safe to take trazodone in the morning and do activities such as driving or lifting objects because the sedative action of trazodone may cause consequences. 

Side effects

Similarly, when the brain chemistry is altered because of trazodone, it causes certain side effects. Some of them are discussed below (1,2):

  • Orthostatic hypotension- Upon standing, trazodone may cause a sudden drop in blood pressure which can cause dizziness and lightheadedness. 


  • Drowsiness and sedation- While the sedative properties of trazodone are therapeutic for insomnia patients, it can also cause daytime drowsiness in patients taking trazodone.  


  • Gastrointestinal distress- Some patients taking trazodone may suffer from gastrointestinal side effects such as nausea, vomiting, constipation, and abdominal discomfort. 


  • Wight changes- Trazodone is associated with causing certain changes in the weight of some patients. 


  • Serotonin syndrome- It is a rare and life-threatening condition that can occur in some patients taking trazodone due to alterations in brain chemicals leading to a surge of serotonin levels. Excessive amounts of serotonin in the brain can cause serotonin syndrome. 

However, every patient taking serotonin might not face all these side effects. It is important to note that individual patient responses to trazodone may vary. Some patients may respond well to trazodone while others may not. 

What to do if trazodone does not help your symptoms?

If trazodone does not help your symptoms, then you must consult your healthcare provider and seek medical help.

Your healthcare provider may help in adjusting your medication dosage as sometimes changing the current dose to either a higher or lower dose may result in more efficacy and better tolerability. 

If you suspect that trazodone is not working well in alleviating your symptoms, your doctor must consider switching you to another safe and well-tolerated antidepressant with fewer side effects and more suitable to your signs and symptoms. 

You must also evaluate your lifestyle. Ensure that you follow a regular physical activity schedule, a balanced diet, and sufficient sleep. These factors play an important role in maintaining good mental health. 

In conclusion, I would add that if you suspect severe adverse effects due to trazodone then consult your doctor and seek medical help. Sometimes dose reduction or change in medication timing may also improve certain side effects. Always consult your doctor before starting or stopping trazodone. 

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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:


AHFS Patient Medication Information [Internet]. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; c2019. Trazodone; [updated 2020 Jun 24; reviewed 2018 Jul 5; cited 2020 Jul 1]; [about 5 p.]. Available from:


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