Can you take Amitriptyline with Sertraline? (+3 benefits)

In this article, we will discuss whether Amitriptyline and Sertraline can be taken together. We will also explore the factors and possible side effects associated with these medications. We will talk about some management strategies for side effects.

Can you take Amitriptyline with Sertraline?

Amitriptyline and Sertraline can be taken together if prescribed by your doctor. This combination is generally used safely by many individuals.

Amitriptyline is a tricyclic antidepressant that is used to treat depression associated with anxiety and primarily inhibits the reuptake of norepinephrine and serotonin.

Sertraline, on the other hand, is a selective serotonin reuptake inhibitor (SSRI) used to treat depression, social anxiety disorder, and psychiatric problems, and it works by blocking the reabsorption of serotonin in the brain. Although the combination of these medications is safe, there are certain significant considerations.

Amitriptyline and Sertraline are administered concurrently and can have potential interactions and effects. Both medications can affect serotonin levels in the brain in different ways. Close monitoring and appropriate dosage adjustments should be undertaken to eradicate the risks of side effects.

Additionally, Sertraline may increase the concentration of Amitriptyline in the body. Amitriptyline is metabolized in the liver primarily by an enzyme; the activity of this enzyme is inhibited by Sertraline.

This can potentially increase the efficacy of sertraline but also raise the risk of side effects associated with Amitriptyline.

Moreover, individuals are different, and they may have various factors that can influence their health condition. What works for one individual may not work for another.

What are the benefits of using Amitriptyline with Sertraline?

Taking Amitriptyline and Sertraline together may help in managing certain types of mental conditions. It is best to seek guidance from your healthcare provider regarding the combination of these medications.

It is necessary to understand that this combination can be complex and should only be used under medical supervision.

Increased Efficacy:

The combination of Amitriptyline and Sertraline may provide symptomatic relief related to depression in certain people in comparison with either medicine used. This combination aims to target various neurotransmitters in the brain, thus improving treatment-resistant depression.

Broadened indications:

Amitriptyline is sometimes prescribed for chronic pain conditions. When Sertraline is given together with Amitriptyline, it may produce profound effects that result in pain relief and mood stabilization (1). It can also be used in the treatment of anxiety, insomnia, and migraines.

Balancing side effects:

The side effects of Sertraline can differ from those of Amitriptyline. For example, certain people experience sexual side effects while using Sertraline, while Amitriptyline may subside these effects.

This combination of medications is certainly based on the careful inspection of every individual according to their health situation.

Potential side effects while taking Amitriptyline and Sertraline together

Sertraline and Amitriptyline can interact with one another when taken together. The potential risks associated with this interaction include:

  • Serotonin Syndrome: One potential risk for this combination of medicines may be an increased probability of side effects. Both Amitriptyline and sertraline enhance serotonin levels and, when taken in combination, can lead to serotonin syndrome which includes symptoms such as confusion, rapid heart rate, high blood pressure, or agitation (1, 3).
  • Amitriptyline has anticholinergic properties, which may lead to side effects like dry mouth, glaucoma, constipation, and urinary retention. When combined with Sertraline, the side effects of both medications may become more prominent (4).
  • These medications can affect heart rate and may increase the risk of arrhythmias. People with existing heart issues may be prone to this combination of medicines, which may increase the incidence of cardiac arrhythmias (5).
  • It reduces blood pressure, resulting in orthostatic hypotension; this combination can enhance the risk of falls.
  • They may have certain contraindications or precautionary measures, particularly for elderly patients and individuals with cardiac problems (2).
  • Additionally, some other side effects associated with this combination can include weight gain, gastrointestinal dysfunction, and metabolic effects. It is necessary to inform your doctor about all the medicines that you are taking, which include vitamins, herbal supplements, and over-the-counter medications, before taking Amitriptyline with Sertraline (2).

It is important to discuss the potential benefits and risks of the combination of Amitriptyline and Sertraline with your doctor before taking it.

They will closely evaluate the medical history, current medicines, and symptoms to determine whether it is appropriate to choose the combination of these medications.

How to manage the side effects of taking Amitriptyline with Sertraline?

Some management strategies for the side effects associated with the combination of Sertraline and Amitriptyline include:

  • Consult your healthcare provider when experiencing adverse effects. If necessary, they will advise on dose adjustments in the dosing regimen.
  • Gradually increasing the dose of these medications under medical supervision.
  • Do not make changes in the dosing regimen by yourself. Follow the instructions provided by your healthcare provider.
  • Overcome the dry mouth effect by staying hydrated throughout the day.
  • Avoid alcohol and caffeine, which can contribute to dry mouth.
  • Take a balanced diet to avoid weight gain.
  • Regular visits to your healthcare provider are necessary to monitor and manage side effects.


To sum up, Amitriptyline can be taken with Sertraline if prescribed by your doctor for managing the symptomatic treatment of depression. While this combination offers benefits, it is important to be cautious about the risks and side effects. To ensure the safety and efficacy of medication, you should inform your healthcare provider.

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Lundmark J, Reis M, Bengtsson F. Therapeutic drug monitoring of sertraline: variability factors as displayed in a clinical setting. Ther Drug Monit. 2000 Aug;22(4):446-54. doi: 10.1097/00007691-200008000-00014. PMID: 10942186.


Lydiard RB, Anton RF, Cunningham T. Interactions between sertraline and tricyclic antidepressants. Am J Psychiatry. 1993 Jul;150(7):1125-6. doi: 10.1176/ajp.150.7.1125b. PMID: 8317590.


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