Does trazodone contain melatonin? (+3 differences)

 In this article, we will discuss whether trazodone formulation contains melatonin. We will also explore the composition of trazodone formulation and highlight the key differences between trazodone and melatonin, including their mechanisms of action, uses, and side effects.

Does trazodone contain melatonin?

No, trazodone does not contain melatonin. Trazodone is an antidepressant drug marketed under various brand names such as Desyrel and Trazodone D. The typical formulation of trazodone contains trazodone hydrochloride as an active ingredient, with different binders, fillers, diluents, and disintegrants added as inactive ingredients or excipients (1).

Melatonin, on the other hand, is a hormone and is entirely different from trazodone. It is often used as a supplement to improve sleep. One well-known formulation containing melatonin is Circadin. Circadin and Adaflex are brand names for melatonin formulations, that incorporate melatonin as the primary active component (3).

What is the difference between trazodone and melatonin?

There is no specific product that combines trazodone and melatonin in a single formulation. These are two distinct therapeutic agents used for various purposes. The key differences between trazodone and melatonin include their mechanisms of action, uses, and side effects, which are discussed below:

Mechanism of action

Trazodone is an antidepressant medication that works by interfering with the levels of serotonin in the brain. It achieves this by inhibiting the reuptake of this neurotransmitter, which is responsible for its therapeutic benefits, including the regulation of mood and behavior in individuals with various mental disorders such as depression and anxiety (1).

Additionally, trazodone may also have an impact on the levels of norepinephrine, although to a lesser extent. Furthermore, this medication has the ability to block certain receptors, including 5-HT-2A and alpha-1-adrenergic receptors, contributing to its therapeutic effects in individuals with insomnia.

 On the other hand, melatonin is a naturally occurring hormone that is also available in the market as a supplement to regulate sleep. It works by activating specific melatonin receptors responsible for regulating the sleep and wake cycle in humans. Additionally, melatonin reduces the levels of dopamine, another neurotransmitter in the brain, which may contribute to keeping you awake (2).

Side effects

While trazodone is generally considered a safe medication with a lower incidence of serious side effects, it may cause some mild to moderate side effects in some individuals. These may include (5):

  • nausea
  • vomiting
  • dizziness
  • drowsiness
  • agitation
  • headaches
  • fatigue
  • dry mouth
  • aggression
  • irritability
  • insomnia
  • weight changes

On the other hand, melatonin is generally considered safe for short-term use, but like any supplement, it may cause side effects in some individuals. Here are some potential side effects of melatonin (4):

  • somnolence
  • stomach discomfort
  • vivid dreams
  • nausea
  • vomiting
  • irritability
  • lightedheadnes
  • low body temperature 


Trazodone is an antidepressant medication that is frequently employed in the management of various health conditions, including mental disorders. Common indications for this medication may include (6):

  • depression
  • anxiety
  • post-traumatic stress disorder
  • obsessive-compulsive disorders
  • panic disorders
  • fibromyalgia
  • chronic pain
  • insomnia

On the other hand, melatonin, although not considered a traditional medication, is widely utilized as a supplement to address diverse sleep-related challenges. It has been commonly employed to mitigate sleep disturbances, alleviate insomnia, counteract the effects of jet lag, and enhance sleep in the elderly (2).

Can you combine trazodone with melatonin? 

Combining both trazodone and melatonin should be approached with caution, considering that both substances are involved in the regulation of sleep. The combination may have additive effects on your sleep, which can impact your health.

Using this combination should only be done under the supervision and guidance of a qualified healthcare professional after a thorough analysis of the risks and benefits. Both trazodone and melatonin share some common side effects, such as dizziness, drowsiness, sedation, and nausea, which may become more pronounced after combining these substances.

The decision to combine them depends on various factors, including your overall health, medical history, and specific sleep-related issues. Additionally, you should not combine these medications without consulting your healthcare provider to prevent unwanted and serious consequences.

In my opinion, the formulation of trazodone typically does not contain melatonin. Since both substances can regulate sleep, their combination should only be considered in cases where the benefits of therapy outweigh the risks.

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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:


Pévet P. Melatonin. Dialogues Clin Neurosci. 2002 Mar;4(1):57-72. doi: 10.31887/DCNS.2002.4.1/ppevet. PMID: 22034091; PMCID: PMC3181670.


Fatemeh G, Sajjad M, Niloufar R, Neda S, Leila S, Khadijeh M. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022 Jan;269(1):205-216. doi: 10.1007/s00415-020-10381-w. Epub 2021 Jan 8. PMID: 33417003.


Savage RA, Zafar N, Yohannan S, et al. Melatonin. [Updated 2022 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


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


Haria M, Fitton A, McTavish D. Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders. Drugs Aging. 1994 Apr;4(4):331-55. doi: 10.2165/00002512-199404040-00006. PMID: 8019056.

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