Adderall With Tramadol Interaction

There are several concerns with this combination.

Question

I take 50mg of tramadol as needed, which for me means maybe once a week. I have just been prescribed Adderall 20mg time release daily. I forgot to ask about the interaction between the two. How long after a tramadol can I take the Adderall and vice versa?

Asked by Alex On Jan 07, 2019

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jan 07, 2019

Interaction Overview

There is a potentially serious interaction between Adderall and tramadol.

There are actually two issues to be aware of if combining these medications:

  • Increased risk of seizures
  • Increased risk of serotonin syndrome

I discuss these in more detail below.

It is important to note that although there are several potential interactions between these two medications, they are sometimes prescribed together and used safely. They shouldn't be combined however unless under the direction of your doctor.

Seizure Risk

Both tramadol and Adderall (amphetamine salts) lower the seizure threshold. Therefore, combining them increases the risk of seizures, especially in those with a history of them.

The prescribing information for Adderall states:

"There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in the absence of seizures, and very rarely, in patients without a history of seizures and no prior EEG evidence of seizures."

Similarly, the prescribing information for tramadol states:

"Seizures have been reported in patients receiving ULTRAM [tramadol] within the recommended dosage range. Spontaneous post-marketing reports indicate that seizure risk is increased with doses of ULTRAM® above the recommended range."

While there haven't been any studies directly assessing the interaction between tramadol and Adderall, several report that both increase the risk of seizure.

In fact, one study evaluating reports of drug-induced seizures found that Adderall and tramadol were both in the top 5 in terms of incidence.

Others studies that look at tramadol-induced seizures specifically list amphetamine as a commonly co-ingested medication thought to contribute to their development.

There are cases where Adderall and tramadol may be prescribed together, but again, you should not take them both if not recommended by your doctor.

Section Summary

Adderall (amphetamine salts) and tramadol can increase the risk of seizures.

Serotonin Syndrome Risk

Tramadol and Adderall have serotonergic properties, meaning they both increase serotonin levels in the brain.

Taking multiple serotonergic drugs increase the risk of a rare, but serious medical condition known as serotonin syndrome. Serotonin syndrome is characterized by a myriad of symptoms, including:

  • Confusion
  • Delirium
  • Increased body temperature
  • Increased blood pressure
  • Muscle rigidity
  • Sweating

Most studies discussing medication induced serotonin syndrome list both amphetamines and tramadol as potential causative factors.

If you do take Adderall and tramadol together, it is important to be aware of the signs of symptoms of serotonin syndrome, especially during treatment initiation and during dosage increases.

Section Summary

Although rare, both Adderall (amphetamine salts) and tramadol have been reported to cause serotonin syndrome. They should not be used together unless recommended and under the supervision of your doctor.

How Long To Wait

There unfortunately isn't a good answer regarding how long to wait in-between doses of tramadol and Adderall to avoid potential interactions.

While we have a good understanding of how each is metabolized, and how long each last in the body, the mechanism behind potential interactions is more complex, especially since they both affect neurotransmitters in the body.

For one example, several studies and medical guidelines state that even after a drug that affects serotonin is completely metabolized and eliminated, it can take considerably longer for our bodies to adjust to a pre-medication level. In fact, it can take serotonin levels several weeks to return to normal concentrations in the brain.

Nevertheless, if you take tramadol and Adderall intermittently, it is beneficial to know how long each last in the body.

Tramadol

The half-life of tramadol is dependent on the specific formulation:

Immediate Release Products: 6.3 to 7.4 hours

Extended Release Products: 10 and 11 hours

The half-life is the time it takes to metabolize 50% of the drug. It typically takes 5-6 half-lives to be completely metabolized and eliminated (although there are exceptions).

Therefore, for tramadol, it will take between 30 and 66 hours (~2-3 days) for it to be eliminated.

If you have any sort of liver impairment, the half-life is greatly extended.

Adderall

The half-life of amphetamine is between 9-13 hours, although this varies depending on the age of the individual and formulation taken.

It will take 2 to 3 days for Adderall to be completely metabolized, a time-frame supported by studies discussing urine drug test detection times.

Section Summary

Both Adderall and tramadol take 2 to 3 days to be completely metabolized, but the risk of an interaction may last longer.

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References
  • Elsevier ClinicalKey: Tramadol Monograph (Accessed 1/7/19)
  • Elsevier ClinicalKey: Adderall Monograph (Accessed 1/7/19)
  • Recognition and treatment of serotonin syndrome. PubMed (Accessed 1/7/19)
  • Serious Reactions with Tramadol: Seizures and Serotonin Syndrome. Link (Accessed 1/7/19)
  • Adderall Package Insert (Accessed 1/7/19)
  • Ultram Package Insert (Accessed 1/7/19)
  • Antidepressant discontinuation syndrome. Pubmed (Accessed 1/7/19)
  • PRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder. Link (Accessed 1/7/19)
  • Urine Drug Screening: A Practical Guide For Clinicians. PubMed (Accessed 1/7/19)


About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor Of Pharmacy degree in 2010. He has been featured in several publications including the Huffington Post as well as a variety of health and pharmacy related blogs. Please feel free to reach out to him directly if you have any questions or want to connect! Brian.Staiger@PharmacistAnswers.com; Office: 716-389-3076

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