Can trazodone interact with amitriptyline?(+9 side effect)

 In this article, we will discuss the interaction between trazodone and amitriptyline. We will also explore the potential adverse effects that may arise from the concurrent use of trazodone and amitriptyline, along with strategies for managing these adverse effects.

Can trazodone interact with amitriptyline?

Yes, trazodone can interact with amitriptyline. When these medications are combined, there is the potential for additive effects, which means the overall impact may be a combination of both drugs’ effects.

This interaction can have both beneficial and harmful aspects for patients. However, it’s crucial to recognize that the interactions between these medications can be complex, leading to effects that are challenging to predict.

Healthcare professionals may consider using this combination for the management of treatment-resistant mental disorders that do not respond to conventional therapy. However, this combination should only be used under the supervision of a qualified healthcare professional to avoid unwanted side effects.

What are the key differences between trazodone and amitriptyline?

Although both amitriptyline and trazodone are antidepressant medications, they may have some key differences, which may include (1,4):

Features Trazodone Amitriptyline
Class Serotonin modulator Tricyclic antidepressant
Indications depression, anxiety, fibromyalgia, pain depression, anxiety, migraine, neuropathic pain
Sedation moderate high
Side effects mild high
Risk low high

What does research suggest?

According to research, the combination of trazodone and amitriptyline may increase the risk of similar side effects associated with these medications.

In a research study, low doses of trazodone and amitriptyline were combined in the management of depression in individuals. This combination was effective in managing the symptoms of depression. However, some individuals reported severe agitation, aggression, restlessness, irritability, and symptoms of anxiety. Some patients also experienced serious symptoms of serotonin syndrome due to the combined effects of these medications on serotonin levels (2).

Another research study reported the occurrence of meiosis in individuals after taking a combination of amitriptyline and trazodone (3).

What are the potential effects of trazodone and amitriptyline interactions?

The potential interactions between trazodone and amitriptyline should be considered cautiously, as both substances can affect the central nervous system, potentially leading to additive effects.

Both trazodone and amitriptyline can increase serotonin levels. When used together, there’s a potential risk of serotonin syndrome, which can be manifested by the following symptoms:

  • agitation
  • hallucinations
  • palpitations
  • temperature changes
  • muscle stiffness
  • impaired coordination

Adverse effects

This combination may also result in additive side effects that may occur when taking these medications alone. However, the risk is increased when combined, potentially leading to serious complications. These side effects may include:

  • excessive sedation
  • impaired cognitive and motor functions
  • dizziness
  • drowsiness
  • nausea
  • vomiting
  • headaches
  • fatigue
  • cardiovascular effects

How to manage the additive side effects of trazodone and amitriptyline?

Managing the potential adverse effects of combining amitriptyline and trazodone can be challenging due to the complex and unpredictable interactions between the two medications.

  • Consult with your healthcare provider to discuss potential dosage adjustments for either medication, aiming to minimize the risk of adverse interactions and side effects.


  • Be cautious, as even lower dosages may lead to additive side effects, especially in susceptible patients.


  • Symptomatic treatment may be necessary to address any side effects that arise from combining amitriptyline and trazodone.


  • Consider exploring alternative therapies and treatments for managing symptoms or conditions for which you are taking trazodone. Your healthcare provider can suggest options with potentially fewer interactions.

 In my opinion, the use of a combination of antidepressant medications should be limited to cases where the benefits of the therapy outweigh its risks and when dealing with resistant mental disorders.

Given that these medications have almost similar mechanisms and side effects, combining them may increase the risk of side effects and lead to additive effects that could worsen symptoms. Always consult your healthcare provider before taking any medication with trazodone to avoid unwanted and serious side effects

Was this helpful?

Thanks for your feedback!



Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Nisijima K, Shimizu M, Abe T, Ishiguro T. A case of serotonin syndrome induced by concomitant treatment with low-dose trazodone and amitriptyline and lithium. Int Clin Psychopharmacol. 1996 Dec;11(4):289-90. doi: 10.1097/00004850-199612000-00013. PMID: 9031998.


Longmore J, Banjar W, Bradshaw CM, Szabadi E. Effects of a controlled-release formulation of trazodone on psychomotor and autonomic functions in healthy volunteers: comparison with trazodone (conventional formulation), amitriptyline and placebo. Eur J Clin Pharmacol. 1988;34(1):97-9. doi: 10.1007/BF01061427. PMID: 3360055.


Thour A, Marwaha R. Amitriptyline. 2023 Jul 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 30725910.

Find a supportive therapist who can help with Depression.

Discover the convenience of BetterHelp, an online therapy platform connecting you with licensed and accredited therapists specialized in addressing issues such as depression, anxiety, relationships, and more. Complete the assessment and find your ideal therapist within just 48 hours.


AskYourPharm is user-supported. We may earn a commission if you sign up for BetterHelp’s services after clicking through from this site