When to Avoid Tramadol

Author: Jill Logan, PharmD
Updated: 1/6/2014

Tramadol: When to avoid it

Take Home Points

Avoid tramadol in:

  • Seizure patients
  • Renal patients
  • Patients taking antidepressants
  • Patients taking warfarin

Tramadol is a popular agent for the treatment of pain and offers an alternative to opioid therapy. Tramadol exerts its analgesic effects through weak stimulation of the mu opioid receptor as well as inhibiting the reuptake of serotonin and norepinephrine similar to some antidepressant medications. While tramadol may be an effective option for mild to moderate pain in otherwise healthy individuals, the following patients may benefit from an alternative analgesic selection:

Seizure patients

Tramadol may lower the seizure threshold thereby potentially increasing seizure frequency in patients at risk or treated for seizures.

Renal Patients

Tramadol requires renal dose adjustment to a frequency of Q 12 hours in patients with CrCl <30 mL/min.

Patients treated with antidepressants

As tramadol exerts serotonin and norepinephrine reuptake inhibition, this may put patients exposed to serotonergic agents at higher risk for serotonin syndrome. While the use of antidepressants and tramadol may be safely used concomitantly, use particular caution with MAO inhibitors and have suspicion for this interaction in patients in potential overdose situations.

NOTE: Linezolid and some Parkinson’s medications fall into the class of MAO inhibiters (although the MAO type B inhibitors may pose less of a risk)

Warfarin Patients

Tramadol will likely lead to an increased INR due to its serotonergic effects as well as other unknown mechanisms.


  • Gardner JS, et al. Tramadol and seizures: a surveillance study in a managed care population. Pharmacotherapy 2000;20(12)1423-31. [PubMed]
  • Park SH, et al. Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants? J Pharm Pract. 2013 Oct 23. [PubMed]
  • Tramadol: Drug Information. Lexi-Comp OnlineTM , Lexi-DrugsTM, Hudson, Ohio: Lexi-Comp, Inc.; December 17, 2013.
  • Nelson LS, Olsen D. Chapter 38. Opioids. In: Nelson LS, Olsen D, eds. Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. Accessed December 17, 2013.