Amitriptyline and Tramadol Interaction

Drug interactions and how to manage them can be very challenging and frustrating.  Let’s take a look at the amitriptyline and tramadol interaction.  Different sources report different potential interactions.

Medscape, both report different interactions on this one.  Medscape reports to monitor for increased serotonin levels as well as look out for both of these medications having sedative properties. which I tend to trust a little less says we should be concerned about monitoring for seizures.

This is the really frustrating part about drug interactions.  Many times there isn’t guidance about the severity and if there is the severity may differ depending upon the program you are using.  So, here is my thought process when looking at interactions like this with conflicting data;

  1. Has the patient been taking these meds for a while or is it a new start?
  2. Are both medications absolutely necessary and/or what alternatives exist?
  3. Does the patient already have a diagnosis that might make this interaction worse (i.e. are you starting tramadol in a patient that already has seizures)?
  4. What evidence, case reports exist?
  5. Dose.  Is the patient being started on a moderate to high dose?  Maybe they shouldn’t be if we are concerned about an interaction.
  6. Anticipate problems and educate the patient about what outcomes or adverse effects may be anticipated from a potential drug interaction.

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  1. Connie

    I would trust lexicomp interactions. According to lexicomp, this is a category D interaction due to excessive sedation. I can see the possibility of seizure risk due to serotonin just like cyclobenzaprine & tramadol. I have seen many patients on this combination, even more with cyclobenzaprine for pain. I personally know of 2 patients who have ‘blacked out’ after taking cyclob and tramadol. I always let the doctor know of the interaction and then if he/she insists on staying the course, then i warn my patients during consultation.

    • Liz Black

      Sloan, Wondering what sort of scam you imply by “scamadol.” Are you saying tramadol is ineffective? I don’t understand and I’d love more info. I’ve heard about seizures as one reason not to mix the two meds, as well as the possibility of serotonin syndrome.
      Thanks in advance.

  2. Nicole Skyer

    Agree. Drug interactions often so hard to predict. Some people more sensitive to serotinergic effects. Not entirely sure why but may be in part pharmacogenomic factors. This interaction related to amitriptyline inhibition of CYP2D6 which may be additive if person is already a poor 2D6 metabolizer. Unfortunately, we usually don’t know a person’s pharmacogenomic status. Love your blog!

    • Eric Christianson

      Thanks so much Nicole 🙂 – Eric

  3. mohammed atiq

    I tend to think that in most cases, people who respond well to SSRI antidepressants should just stay on them – they have been proven to work.
    They also come with unwanted side effects and many people have gone through the entire wringer of medications only to find no relief.

  4. Ramesh

    I’ve had a head injury in 2017 and Doctors didn’t know how to fix my neck and back pain so then turned me to Endep as there were no signs to be seen off the MRI/Cat scans but has parathesia and over 12 months of post concussion migraines. It helped but I can’t only handle a few weeks at a time but it works for a few months to at a time but the issues is I did my sciatic nerve so have to use Tramadol but Ive read both cannot be used so if both issues are playing up I suffer.


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Written By Eric Christianson

January 11, 2017

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