Can trazodone and Seroquel be taken together? (+3 risks)

In this article, we will discuss whether trazodone and Seroquel can be taken together. We will discuss the potential risks and benefits of taking these medications together and other relevant information. 

Can trazodone and Seroquel be taken together? 

Trazodone and Seroquel can be taken together if prescribed by the healthcare provider. Research on their concomitant use is limited but Seroquel is often prescribed with antidepressants like trazodone. 

Trazodone, an antidepressant, is categorized as a serotonin antagonist and reuptake inhibitor (SARI). It is primarily used for major depressive disorder (MDD) and is FDA-approved for this purpose. It is also used for insomnia as it causes sedation (1).

The active ingredient in Seroquel is quetiapine which is an atypical antipsychotic. FDA has approved this medication for schizophrenia and bipolar disorder and to manage manic and depressive episodes in bipolar disorder (2). 

The use of trazodone with Seroquel is plausible because Seroquel can be prescribed with antidepressants and as an adjunct treatment for several forms of MDD. However, they should only be used together under medical oversight.

What does research suggest?

The research on the concomitant use of trazodone and Seroquel is limited. However, Seroquel has been used with other antidepressants for different conditions. Thus, trazodone and Seroquel may be prescribed together. 

Research indicates that not more than 35% of patients achieve full remission from depression when treated with a single antidepressant even when maximum therapeutic doses are used for an adequate duration (3). 

To achieve a total absence of depressive symptoms, drugs like Seroquel are used along with other antidepressants for an enhanced antidepressant effect. Seroquel, along with its FDA-approved indications is used as an adjunctive treatment (3). 

Seroquel can complement the treatment of MDD with other antidepressants, and also treat depression in which the individual has psychotic features. Studies have shown that combined therapy with Seroquel is effective for MDD (3). 

Seroquel has been paired with different antidepressants like citalopram, paroxetine, and venlafaxine for the improvement of depression and maintenance of remission. 

Thus, the research suggests that Seroquel can be combined with antidepressants for better outcomes. Therefore trazodone and Seroquel may be prescribed together by your healthcare provider. 

It is important to remember that Seroquel and trazodone both are prescription drugs and should not be used together unless prescribed by the healthcare provider. Their inappropriate use is dangerous and results in adverse effects. 

What are the potential benefits of using trazodone with Seroquel?

Trazodone and Seroquel help to regulate those neurotransmitters that are involved in depression and other mental disorders. The potential benefits of using trazodone with Seroquel are as follows:

Enhanced antidepressant effect: 

Trazodone and Seroquel both have a complex mechanism of action and act on different neurotransmitters. Trazodone inhibits serotonin reuptake and blocks some serotonin, histamine (H1), and alpha-1 adrenergic receptors (1). 

Seroquel acts on serotonin and dopamine receptors and regulates their levels. It has antagonistic action on serotonin 5-HT2 and dopamine D2 receptors (2).

Overall, trazodone and Seroquel regulate neurotransmitters like serotonin that are involved in the regulation of behavior, mood, and perception. The combination of trazodone and Seroquel results in enhanced antidepressant effects. 

Enhanced symptom management:

Seroquel has been effective in managing different symptoms that can occur with MDD including anxiety, agitation, and insomnia. Using Seroquel with trazodone can address multiple symptoms that appear with MDD (3). 

Studies have shown that Seroquel is effective in managing treatment-resistant depression, depression with psychosis, and anxiety in MDD when used with other antidepressants (3). 

Thus, using trazodone and Seroquel together can help manage multiple aspects of mental health conditions and can be a promising approach for comprehensive symptom management. 

What are the risks of using trazodone with Seroquel? 

Using trazodone and Seroquel together is associated with the following risks:

Risk of serotonin syndrome:

Trazodone and Seroquel both regulate serotonin concentration in the body. Higher than-normal concentrations of serotonin in the body result in a lethal condition known as serotonin syndrome.

Using trazodone with other serotonergic drugs increases the risk of serotonin syndrome. Seroquel also increases serotonergic transmission (4) and using it with serotonergic drugs can cause serotonin syndrome. 

Research shows that using Seroquel with serotonergic drugs has caused serotonin syndrome when the dose of Seroquel was slightly increased (5). Thus, careful dose adjustment is required if trazodone and Seroquel are prescribed together. 

Symptoms of serotonin syndrome include (6):

  • mental status alteration
  • agitation
  • excessive salivation
  • excessive sweating
  • hyperthermia
  • dizziness
  • tremors
  • seizures
  • hallucinations

Enhanced sedation:

Trazodone and Seroquel both are used off-label for insomnia. This is because they induce sedation in low doses by interacting with histamine and serotonin receptors (1,2). Thus, using trazodone and Seroquel together enhances the sedative effect. 

Combined use of trazodone and Seroquel can result in daytime drowsiness and impair cognition and alertness if their doses are not adjusted properly. 

Enhanced cardiovascular effects: 

Trazodone can prolong the QT intervals in patients and result in arrhythmia (1). Seroquel and trazodone both are advised to be used with precaution with drugs that prolong QT intervals (2,6). 

Monitoring of QT intervals is recommended in patients using Seroquel. This indicates that using trazodone and Seroquel together can increase the risk of QT prolongation and arrhythmia. Both drugs can cause orthostatic hypotension (1,2). 

Enhanced side effects: 

Trazodone and Seroquel both are associated with their respective set of side effects. Taking them together enhances the occurrence of side effects and amplifies the shared side effects. Trazodone-associated side effects include (1):

  • somnolence
  • lightheadedness
  • suicidal thoughts
  • tiredness
  • QT prolongation
  • priapism
  • orthostatic hypotension
  • arrhythmia
  • acid reflux

Seroquel-associated side effects include (2):

  • somnolence
  • abdominal pain 
  • lightheadedness
  • constipation
  • orthostatic hypotension
  • suicidal thoughts
  • tachycardia
  • dry mouth

Trazodone vs Seroquel: which one is more effective for insomnia? 

Trazodone and Seroquel are used off-label for insomnia and their efficacy, safety, and tolerability are being explored for insomnia. The response to each medication depends on individual characteristics and symptoms.  

In one study, the efficacy of trazodone and Seroquel were compared in treating insomnia. Results indicated that trazodone was more effective in improving sleep and associated with more gastrointestinal side effects than Seroquel (7). 

It is important to remember that the primary and FDA-approved uses of trazodone and Seroquel are different and they are not the first-line treatment of insomnia.

Your healthcare provider will decide the medication suitable for you based on your health condition. Usually, Seroquel is preferred when insomnia occurs along with mood or schizophrenia spectrum disorders. 

Trazodone is preferred for insomnia when it occurs along with MDD. It can also be used when insomnia occurs as a side effect of other antidepressants. 

In my perspective, trazodone and Seroquel can be used together if prescribed by a healthcare provider. Seroquel has been used as an adjunctive treatment for MDD and is prescribed with several antidepressants. 

Using Seroquel with antidepressants has been effective in treating treatment-resistant depression and anxiety, agitation, and insomnia occurring in patients with MDD. 

Thus, trazodone and Seroquel can be used together to enhance the antidepressant effect and address multiple symptoms of depression. Due to the associated risks, the medications should be used together only if prescribed by the healthcare provider. 

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