Adderall With Elavil (Amitriptyline) Interaction

In our latest question and answer, the pharmacist discusses the interaction between Adderall (amphetamine salts) and Elavil (amitriptyline).

Adderall With Elavil (Amitriptyline) Interaction
Jan 21, 2019

Shawn asked

My doctor put me on 10 mg of Elavil for Levator ani syndrome. I taper down slowly over a month after each episode and usually go for 8-10 months with no issue. Problem is, I stop taking Adderall during this time due to the interaction. I usually take 30 mg of the immediate release Adderall about 3-4 days a week. I find that without it, especially while taking Elavil, that I am very tired and cannot concentrate. What exactly is the interaction and would a smaller dose of stimulant be safer?

At a glance

  • There is a potential interaction between Adderall (amphetamine salts) and Elavil (amitriptyline). Taking both can increase cardiovascular side effects and the risk of serotonin syndrome. The combination has been used safely but should only be done under the direction and supervision of your doctor.


Drug Interaction Arrows

Taking amphetamine products, like Adderall, with Elavil (amitriptyline) increases the risk of a rare but serious condition known as serotonin syndrome.

Serotonin Syndrome

Amitriptyline is classified as a 'tricyclic antidepressant' or TCA. These drugs inhibit the reuptake of various neurotransmitters in the brain, including serotonin.

Amphetamines like Adderall, not only inhibit the reuptake of serotonin as well but also increase serotonin release. The net result of this interaction is increased concentrations of serotonin in the brain.

Too high levels of serotonin can cause 'serotonin syndrome', which is characterized by the rapid development of a variety of symptoms, including:

  • Increased body temperature
  • Sweating
  • High blood pressure
  • Muscle rigidity
  • Dizziness
  • Fainting
  • Mental status changes
Serotonin Symptom Chart
Source: Shutterstock

In addition to the effects on serotonin, amitriptyline and Adderall can increase concentrations of another neurotransmitter, norepinephrine. Norepinephrine can increase blood pressure and heart rate. Therefore, taking both amitriptyline and Adderall could increase the risk of cardiovascular effects.

Having said all of the above, tricyclic antidepressants like amitriptyline and amphetamine products are used in combination together in practice fairly often.

In fact, several studies suggest the combination of antidepressants like amitriptyline and stimulants like Adderall can be very effective, and relatively safe, for the treatment of 'treatment-resistant depression'.

Just how risky the combination isn't well known.

Most studies that discuss serotonin syndrome as a general topic will list both tricyclic antidepressants and stimulants as potential causative factors. Nevertheless, the risk appears relatively low for most people taking amitriptyline and Adderall specifically.

While caution should be exercised when using both of these drugs, the combination is considered a lower risk than others since the serotonin effects of amphetamine and amitriptyline aren't all that strong.

While amitriptyline does have some effects as a serotonin reuptake inhibitor, it is classified as a weak inhibitor. One study, published in the Canadian Family Physician, states the following:

  • Elsevier ClinicalKey: Adderall (Accessed 1/21/19)
  • Elsevier ClinicalKey: Elavil (Accessed 1/21/19)
  • Serotonin syndrome and other serotonergic disorders. PubMed (Accessed 1/21/19)
  • Serotonin Syndrome. PubMed (Accessed 1/21/19)
  • Demystifying serotonin syndrome (or serotonin toxicity). PubMed (Accessed 1/21/19)
  • The scoop on serotonin syndrome. PubMed (Accessed 1/21/19)
  • Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. PubMed (Accessed 1/21/19)
  • The scoop on serotonin syndrome. PubMed (Accessed 1/21/19)
  • Psychostimulants in the therapy of treatment-resistant depression Review of the literature and findings from a retrospective study in 65 depressed patients. PubMed (Accessed 1/21/19)

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