TramadolTramadol 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. 1–4

Patient PopulationTramadol Effect
Seizure patientsTramadol may lower the seizure threshold thereby potentially increasing seizure frequency in patients at risk or treated for seizures.
Renal patientsTramadol requires renal dose adjustment to a frequency of Q 12 hours in patients with CrCl < 30 mL/min.
Patients treated with antidepressantsAs 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.*
Warfarin patientsTramadol will likely lead to an increased INR due to its serotonergic effects as well as other unknown mechanisms.
* 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)


Tramadol: Drug Information. Lexi-Comp OnlineTM , Lexi-DrugsTM, Hudson, Ohio: Lexi-Comp, Inc.; December 17, 2013.
Park S, Wackernah R, Stimmel G. Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants? J Pharm Pract. 2014;27(1):71-78. [PubMed]
Gardner J, Blough D, Drinkard C, et al. Tramadol and seizures: a surveillance study in a managed care population. Pharmacotherapy. 2000;20(12):1423-1431. [PubMed]
Nelson L, Lewin N, Howland M Ann, Hoffman R, Goldfrank L, Flomenbaum N. Opioids. In: Goldfrank’s Toxicologic Emergencies, Ninth Edition. 9th ed. Mcgraw-Hill; 2010:559-578.
Jill Logan, PharmD BCPS

Jill Logan, PharmD BCPS

Clinical Pharmacy Specialist, Emergency Medicine
University of Maryland Medical Center
Jill Logan, PharmD BCPS

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