Three Reasons You Should Avoid Tramadol

Reason #1 -  It May Not Work

Previous data from a variety of non-emergent settings suggests that tramadol may provide better pain relief than pure placebo. In a study of patients with chronic back pain, Schnitzer et al. reported lower pain scores in patients who received tramadol when compared to those who were given placebo [1]. In a prospective study of patients with acute abdominal pain, patients were randomized to receive either tramadol, acetaminophen (paracetamol) or placebo. Patients who received tramadol or acetaminophen reported a significant decrease in pain scores when compared to patients in the placebo group. [2].

In prospective study of patients presenting to the ED with acute musculoskeletal pain, patients who received tramadol reported higher pain scores across a range of time intervals when compared to patients who were given a combination product containing hydrocodone and acetaminophen [3].

In a 2005 review, Sachs et al. examined various oral analgesics, concluding that due to inferior efficacy and an unfavorable side effect profile, tramadol should not be used as a first line agent in the treatment of acute pain [4].


Reason #2 - It May Hurt Our Patients

There are several significant potential risks associated with the use of tramadol.

Risk of Erratic Metabolism

Tramadol’s active metabolite, M1, is created after tramadol is metabolized by the CYP2D6 enzyme [5]. As with other analgesics such as codeine, a subset of the population suffers from abnormal activity of this enzyme.

Risk of Seizure

Tramadol appears to pose an increased risk of seizure. Labate et al. reported that 8.2% of cases occurred after exposure to tramadol[6]. Risk of Hypoglycemia study, Fournier et al. reported that when compared to patients taking codeine, patients who received tramadol had significant increase in the risk of hypoglycemia that required a hospitalization. [7].

Risk of Serotonin Syndrome

When abused or used in conjunction with other agents that limit serotonin reuptake, such as SSRIs, tramadol can increase the risk of a patient developing serotonin syndrome.. Providers should use caution when prescribing to patients who are taking other agents that may limit serotonin re-uptake[8].


Reason #3 - It Isn’t A “Safe” Opioid

In a 2010 letter to healthcare professionals cautioned against using tramadol in patients who are prone to addiction or with a history of suicidal ideation [9][10] Tramadol poses several unique risks when abused, particularly in the setting of an overdose. Compared to alternative agents, tramadol may cause significant complications after even relatively minor ingestions with reports of significant neurotoxicity occurring after ingestions of as little as 5 times the recommended dose. As only a small portion of these symptoms come from the opioid receptor, traditional antagonists such as naloxone have limited efficacy when used to treat a tramadol overdose [11].


Tired of reading?  Watch Matthew Delaney, MD, FACEP, discuss Tramadol use in the ED during our 2016 Winter Symposium


Written by Matthew Delaney, M.D.

Edited and Posted by Jeffrey Holmes, M.D.


1. Schnitzer TJ, Gray WL, Paster RZ, et al. Efficacy of tramadol in treatment of chronic low back pain. J Rheumatol. 2000 Mar;27(3):772-8.

2. Oguzturk H, Ozgur D, Turtay MG, et al. Tramadol or paracetamol do not effect the diagnostic accuracy of acute abdominal pain with significant pain relief - a prospective, randomized, placebo controlled double blind study. Eur Rev Med Pharmacol Sci. 2012 Dec;16(14):1983-8.

3. Turturro MA, Paris PM, Larkin GL. Tramadol versus hydrocodone-acetaminophen in acute musculoskeletal pain: a randomized, double-blind clinical trial. Ann Emerg Med. 1998 Aug;32(2):139-43.

4. Sachs CJ. Oral analgesics for acute nonspecific pain. Am Fam Physician. 2005;71:913-8.

5. Leppert W. CYP2D6 in the metabolism of opioids for mild to moderate pain. Pharmacology. 2011;87(5-6):274- 85.

6. Labate A, Newton MR, Vernon GM, et al.. Tramadol and new-onset seizures. Med J Aust.2005;182:42-44.

7. Fournier JP, Azoulay L, Yin H, et al. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain. JAMA Intern Med. 2015 Feb;175(2):186-93.

8. Sansone RA, Sansone LA. Tramadol: seizures, serotonin syndrome, and coadministered antidepressants. Psychiatry (Edgmont). 2009 Apr;6(4):17-21.

9. Tramadol: Important Drug Warnings. Ortho-McNeil-Janssen Pharmaceuticals, Inc.; March 2010. Available at: ts/UCM213265.pdf

10. Senay EC, Adams EH, Geller A, et al. Physical dependence on Ultram® (tramadol hydrochloride): both opioidlike and atypical withdrawal symptoms occur. Drug Alcohol Depend 2003;69:233-4.

11. Spiller HA, Gorman SE, Villalobos D, et al. Prospective multicenter evaluation of tramadol exposure. J Toxicol Clin Toxicol. 1997;35:361-364.