Does trazodone interact with phentermine? (+tips)

This article will discuss the potential interaction between two medications, trazodone and phentermine. It explores their mechanisms of action, the possible interactions and side effects when taken together, and provides recommendations for safe usage.

Additionally, the article addresses the benefits and considerations of combining these medications.

Does trazodone interact with phentermine?

Trazodone and phentermine may interact, but there have been no case studies or reports of any such interaction. Trazodone has a calming effect and is primarily used to treat depression and insomnia, while phentermine is commonly prescribed as an appetite suppressant for weight loss.

Both drugs stimulate the central nervous system, and combining them may increase the risk of sympathetic side effects. However, individual responses to medications can vary, and not everyone who takes trazodone and phentermine together will experience increased side effects or interactions.

If you experience any unusual symptoms while taking these medications together, it is important to seek medical attention immediately. It is also recommended to consult with a doctor before combining these medications to carefully consider potential risks.

How can trazodone and phentermine interact?

Phentermine is classified as a sympathomimetic amine and works similarly to amphetamines. It triggers the release of norepinephrine and epinephrine, stimulating the central nervous system and suppressing appetite, which can aid in weight loss [1].

Trazodone, on the other hand, is a serotonin antagonist and reuptake inhibitor (SARI). It acts by inhibiting both the serotonin transporter and serotonin type 2 receptors. It therefore prevents the reuptake of serotonin and also blocks histamine and alpha-1-adrenergic receptors [2].

At lower doses, trazodone’s sedating and hypnotic effects are mainly observed due to its antagonistic effects on serotonin type 2 receptors, adrenergic receptors, and histamine receptors. However, at higher doses, trazodone’s inhibition of serotonin reuptake becomes more prominent [2].

This leads to an increase in serotonin levels, potentially contributing to its antidepressant effects. Therefore, if trazodone is prescribed at low doses to act as a hypnotic, phentermine’s sympathomimetic action may counteract trazodone’s effects and decrease its effectiveness [2].

If trazodone is used at high doses for depression and leads to an increase in serotonin, it may cause an increase in similar side effects [2].

What are the possible interactions between trazodone and phentermine?

There are minimal, mild, insignificant, and rare interactions between these two medications, but it is important to be aware of them.

Risk of headaches

Headache is among some of the less common side effects of trazodone. However, since phentermine is commonly associated with headaches, taking these drugs together potentiates the risk of headaches [3,4].

Risk of heart problems 

Moreover, both trazodone and phentermine may cause different types of arrhythmias through different mechanisms. Therefore, people with heart problems may be at risk of heart complications if they take these medications together [3,4].

Risk of increased weight loss

Additionally, trazodone may cause nausea, vomiting, loss of appetite, and weight loss as a side effect. Since phentermine also causes weight loss, combining these medications may potentially lead to excessive weight loss and being underweight.

Decreased efficacy of trazodone 

Furthermore, as previously mentioned, phentermine’s sympathomimetic action may counteract trazodone’s sedating effects, consequently decreasing its therapeutic benefit as a drug for insomnia.

It is also important to mention that taking high doses of both drugs together may cause serotonin syndrome, a very dangerous condition that leads to confusion, sweating, high blood pressure, tremors, seizures, and more.

Despite these potential interactions and side effects, it is worth pointing out that these drugs are still generally very safe to combine, and these symptoms are usually mild and rare.

Pharmacokinetic interactions

Phentermine and trazodone do not directly affect each other’s metabolism or excretion. However, it is important to note that both are metabolized through Cytochrome P450 (CYP) 3A4 enzymes [3,4].

Therefore, individuals who are deficient in these enzymes may experience increased potency of either drug if taken together. However, it is unlikely that this interaction will cause any significant additional harm.

What are the benefits of combining trazodone and phentermine?

There are currently no studies available on the therapeutic benefits of combining these two medications. Additionally, there is no clear indication that combining them is beneficial.

However, considering that phentermine is known to cause insomnia, taking trazodone alongside it may potentially reduce this side effect.

This approach could potentially improve patient adherence to phentermine treatment, allowing for longer treatment durations or higher doses while still maintaining the safe administration of phentermine without the presence of insomnia.

Moreover, incorporating trazodone into the treatment regimen may ensure a better overall quality of life and improved patient satisfaction, as trazodone is highly effective in treating insomnia. However, you should never take these medications together without consulting with a doctor first.

How can you take trazodone and phentermine safely?

To safely take both of these medications together, it is advisable to follow your doctor’s instructions precisely. It is generally recommended to take phentermine on an empty stomach before breakfast or 1 to 2 hours afterward.

Regarding trazodone, it is suggested to start with a low dose and gradually increase it under medical supervision until achieving the desired response. However, you must not exceed the maximum tolerable dose, which is 400 mg. Moreover, it is recommended to take trazodone after a meal.

Additionally, as phentermine is known to potentially cause insomnia, which goes against the intended use of trazodone, it is recommended to avoid taking phentermine in the evening. Taking phentermine in the evening may lead to insomnia and counteract the effects of trazodone.


In conclusion, I found that there have been no reported case studies or reports of interactions between trazodone and phentermine.

However, I believe that individual responses to medications can vary, and it is always recommended to seek medical attention if you experience any unusual symptoms while taking these medications together.

Based on my knowledge, some possible interactions include headaches, heart problems, increased weight loss, and decreased efficacy of trazodone’s hypnotic effect. However, these interactions and side effects are usually mild and rare. 

Furthermore, I believe that taking trazodone alongside phentermine may potentially reduce phentermine-induced insomnia, which could improve patient adherence and overall quality of life.

To take trazodone and phentermine safely, I recommend following your doctor’s instructions precisely, taking phentermine in the morning, and starting trazodone with a low dose and gradually increasing it under medical supervision. 

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Johnson DB, Quick J. Topiramate and Phentermine. [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:,prophylactic%20treatment%20of%20migraine%20headaches.


Stahl SM. Mechanism of Action of Trazodone: a Multifunctional Drug. CNS Spectrums. 2009;14(10):536-546. doi:10.1017/S1092852900024020


Highlights of Prescribing Information. TRAZODONE HYDROCHLORIDE tablets, for oral use. Initial U.S. Approval: 1981.


Phentermine Prescribing Information. Phentermine Hydrochloride Tablets, USP.

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