Can you take Prozac in the morning and Trazodone at night?

In this article, we will discuss taking Prozac (Fluoxetine) in the morning and Desyrel (Trazodone) at night – both of which are antidepressants. We will also talk about the potential benefits and risks of this combination. 

Can you take Prozac in the morning and Trazodone at night?

You can take Prozac in the morning and Trazodone at night, but only if prescribed by your healthcare provider. The combination of a selective serotonin reuptake inhibitor (SSRI), such as Prozac, and Trazodone is prescribed quite frequently these days (1). 

Both of these medications are antidepressants which work differently to balance the amount of excitatory chemicals in the brain to help manage symptoms associated with depression and anxiety (2,3). 

Although taking Prozac in the morning and Trazodone at night can offer some potential benefits, it is not the right treatment choice for every individual.

What does research suggest?

Several researchers studied the combination of Prozac and Trazodone and observed various outcomes. One research study explored the interaction between Fluoxetine and Trazodone in treating depression (4). 

It found that Fluoxetine can increase the levels of Trazodone in the body, which may enhance the antidepressant effects of this combined treatment. 

This suggests that the combination of Fluoxetine and Trazodone may be more effective in managing depression due to these increased drug levels (4). 

Another research study explained that adding Trazodone to Fluoxetine affected depressed patients. They found that for about 37.5% of the patients, this combination improved both sleep and depression (5). 

However, the remaining patients either didn’t benefit from it or experienced side effects. So, while Trazodone can be helpful for some, it may not work for everyone and can have adverse effects (5). 

Another research study looked into the effects of combining Fluoxetine and Trazodone in pharmacotherapy. The combination led to severe negative reactions in some individuals, including irritability, anger, anxiety, and loss of appetite. These adverse effects are likely due to an interaction between the two drugs (6).

Potential benefits of taking Prozac in the morning and Trazodone at night

Taking Prozac in the morning and Trazodone at night can have some potential benefits. Prozac, when taken in the morning, can help improve mood and alleviate symptoms of depression during the day by regulating brain chemicals related to mood. 

Trazodone at night can promote better sleep and reverse Prozac-induced insomnia, which is essential for overall well-being (7). This combination can offer enhanced antidepressant effects and better nighttime sleep, making it a valuable option for managing depression and sleep disturbances.

Potential risks of taking Prozac in the morning and Trazodone at night

There are some potential risks associated with taking Prozac in the morning and Trazodone at night. The two antidepressants may cause additive side effects. 

Furthermore, improperly adjusted doses or taking two medications with a small time interval can increase the risk of serotonin syndrome (8). 

It is a rare condition and very high doses of antidepressants lead to this syndrome, but people are different and may react differently to this combination. 

Some people may also take other medications which may or may not affect serotonin levels in the brain. This can also increase the chances of drug-drug interactions. 


Taking Prozac in the morning and Trazodone at night can offer potential benefits, and some people respond really well to this combination. However, it’s not for everyone. Just like one shoe can’t fit all of us, this medication combination may not suit every individual’s needs.

Our bodies and minds are as unique as our fingerprints, so what works for one person might not be the right fit for another. That’s why it’s crucial to consult with a healthcare professional before starting or changing any medication regimen.

Your doctor has full access to your medical history and knows about your symptoms. he/she will determine the best treatment strategy to manage your symptoms in a safe and effective way. Just make sure you properly follow your doctor’s directions.

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Clark NA, Alexander B. Increased rate of trazodone prescribing with bupropion and selective serotonin-reuptake inhibitors versus tricyclic antidepressants. Ann Pharmacother. 2000 Sep;34(9):1007-12. doi: 10.1345/aph.19101. PMID: 10981245.


Sohel AJ, Shutter MC, Molla M. Fluoxetine. 2022 Jul 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 29083803.


Shin JJ, Saadabadi A. Trazodone. 2022 Jul 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 29262060.


Maes M, Westenberg H, Vandoolaeghe E, Demedts P, Wauters A, Neels H, Meltzer HY. Effects of trazodone and fluoxetine in the treatment of major depression: therapeutic pharmacokinetic and pharmacodynamic interactions through formation of meta-chlorophenylpiperazine. J Clin Psychopharmacol. 1997 Oct;17(5):358-64. doi: 10.1097/00004714-199710000-00004. PMID: 9315986.


Nierenberg AA, Cole JO, Glass L. Possible trazodone potentiation of fluoxetine: a case series. J Clin Psychiatry. 1992 Mar;53(3):83-5. PMID: 1548249.


Amin R. Fluoxetine and Trazodone Combination Pharmacotherapy Resulting in Severe Irritability, Anger, Anxiety, and Anorexia: Probable Adverse Drug Interaction. Prim Care Companion CNS Disord. 2016 Aug 11;18(4). doi: 10.4088/PCC.15l01917. PMID: 27828706.


Nierenberg AA, Adler LA, Peselow E, Zornberg G, Rosenthal M. Trazodone for antidepressant-associated insomnia. Am J Psychiatry. 1994 Jul;151(7):1069-72. doi: 10.1176/ajp.151.7.1069. PMID: 8010365.


Simon LV, Keenaghan M. Serotonin Syndrome. 2023 Jul 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 29493999.

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