Interaction Between Cymbalta (Duloxetine) And Elavil (Amitriptyline)

In our latest question and answer, the pharmacist discusses the drug interaction between Cymbalta (duloxetine) and Elavil (amitriptyline).


I am taking Cymbalta 30 mg due to sciatica in the morning. I have been on Elavil 50 mg at night for tinnitus, is this safe?

Asked by Sandra On Jun 21, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jun 22, 2018

Cymbalta (duloxetine) and Elavil (amitriptyline) do have a major drug interaction and should be used together with extreme caution. Although not contraindicated to take together, taking Elavil and Cymbalta increases the risk of serotonin syndrome.

Serotonin syndrome is the name given to a certain group of symptoms that can occur with the use of serotonergic drugs (i.e. drugs that increase serotonin). The symptoms can range from mild to severe and include but are not limited to the following:

  • Hyperthermia
  • Shaking/tremors
  • Nausea
  • Vomiting
  • Agitation
  • Delirium
  • Confusion
  • Rapid heart rate
  • Coma 

In addition to the risk of serotonin syndrome, Cymbalta is an inhibitor of the metabolizing enzyme CYP2D6, which metabolizes Elavil. Therefore, Elavil concentrations can be increased when taken with Cymbalta, increasing the risk of side effects.

It should be noted that sometimes Elavil is given in a low does for treatments other than depression (such as for insomnia and tinnitus). The risk of the interaction with Cymbalta is certainly lower when taken with low doses of Elavil but not eliminated. It is important to be aware of the risks of taking the drugs together as well as the side effects to look out for. Be sure to report any adverse effects to your doctor.

About the Pharmacist

Dr. Adam DeRue Pharm.D

Dr. Adam DeRue is a Doctor Of Pharmacy and registered pharmacist.

About Cymbalta (Duloxetine)

Cymbalta (duloxetine) is an antidepressant, belonging to the Serotonin-Norepinephrine Reuptake Inhibitor class, which work by inhibiting the reuptake of both serotonin and norepinephrine and are often referred to as a 'dual' inhibitors. Cymbalta has been shown to be effective in treating symptoms of depression as well as painful neuropathy due to the effects on norepinephrine. Like most antidepressants, Cymbalta can take 4 to 12 weeks to reach full effect and should be taken consistently. Cymbalta is generally dosed once daily and can be administered without regard to meals.

About Elavil (Amitriptyline)

Elavil (amitriptyline) is a tricyclic antidepressant (TCA), which is metabolized in the body to the active metabolite nortriptyline. The exact mechanism of action of amitriptyline is not fully understood, but is thought to increase levels of of norepinephrine and serotonin. Amitriptyline is used for a wide range of indications including depression, anxiety and insomnia. Compared to other antidepressants, amitriptyline is generally more sedating and has greater anticholinergic effects, which increases the risk of side effects such as constipation, dry mouth and confusion, especially in the elderly.

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