Three Reasons Not to Prescribe Tramadol

Emergency Medicine PharmD: Three Reasons Not to Prescribe Tramadol

Once again, a medication that was supposed to be a safer alternative to opioids proved to be neither; not only does it not mitigate the addiction risk, it isn’t even effective.

This is a perfect example of the inferior medical care we pain patients receive, forced to endure ineffective and possibly dangerous medication because it is becoming taboo to prescribe the only medicine that works best, old-fashioned opioids.

Tramadol is a commonly prescribed analgesic that is used to treat a wide variety of painful conditions. Through a somewhat unique mechanism of action, tramadol acts as a mu-opioid receptor agonist and serves as an antagonist to serotonin and norepinephrine receptors.

When compared to traditional opioids, tramadol, and its active metabolite M1 (O-desmethyltramadol) bind the mu-opioid receptor with 10 times less affinity than codeine and approximately 100 times less affinity than morphine

While the weak agonist effect of tramadol is thought to provide some pain relief, the inhibition of serotonin and norepinephrine reuptake is thought to provide added analgesia while limiting some of the known adverse effects associated with traditional opioids.

Tramadol has been marketed as a novel analgesic that offers pain relief comparable to opioids without the associated risks of abuse or dependency. As its use has increased, there is emerging data to suggest that tramadol is not a medication that should be routinely used.  

From questionable efficacy, risk of dependency/abuse, to a somewhat unique risk of complications, there are three major reasons why providers should be careful when using tramadol.

1 – It May Not Work

To date, there is very limited data in terms of the efficacy of tramadol compared to placebo when used in the emergency departmen

There is little evidence to suggest that tramadol provides better pain relief than acetaminophen or ibuprofen.

Tramadol does not appear to match the analgesic properties of traditional opioids. 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

Overall there is very little evidence that tramadol is more efficacious than any other commonly available analgesics.

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

As with other analgesics such as codeine, a subset of the population suffers from abnormal activity of this enzyme and is at an increased risk of adverse event when taking tramadol.

Risk of Seizure

. While multiple analgesics are reported to lower a patient’s seizure threshold, there is emerging data to suggest that this risk may pose an even heightened risk.

Risk of Hypoglycemia

patients who received tramadol had significant increase in the risk of hypoglycemia that required a hospitalization. The relationship between tramadol and hypoglycemia is still somewhat unclear; however, providers should be aware of this association

Risk of Serotonin Syndrome

When abused or used in conjunction with other agents that limit serotonin reuptake, such as selectiveserotonin reuptake inhibitors, tramadol can increase the risk of a patient developing serotonin syndrome

3 – It Isn’t A “Safe” Opioid

there is increasing evidence that tramadol may pose a significant risk of abuse, dependency, and withdrawal in a certain subset of patients

Due in a large part to this emerging risk of abuse, tramadol has been reclassified as a Schedule IV substance by the DEA [14].

There is a high rate of neurotoxicity including seizures and lethargy when patients overdose on tramadol that is thought to be due to the blockade of serotonin and norepinephrine re-uptake rather than coming strictly from the opioid agonist activity.

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 .


Despite its widespread use, there are significant issues that providers should consider before using tramadol.

In terms of efficacy tramadol has not been shown to consistently outperform other available analgesics.

In addition, tramadol has a set of potential side effects that make it a less than ideal first line analgesics.

Finally tramadol does not appear to be a “safe opioid” as there seem to be significant potential for abuse, dependency, and withdrawal.


8 thoughts on “Three Reasons Not to Prescribe Tramadol

  1. Pingback: Three Reasons Not to Prescribe Tramadol | All Things Chronic

    1. Zyp Czyk Post author

      I was prescribed tramadol way back in 1994 and it had no noticeable effect on me. They told me at the time that for most patients, it either worked well or not at all.

      Nowadays, tramadol is becoming popular just because it’s a way to get around prescribing “real” opioids. Nature has designed our bodies with endogenous opioids (and endocannabinoids) and provided plants providing the same for us to use as supplements. Science still can’t do any better.


  2. Gillian Dempsey

    For some of us with EDS Tramadol is the only painkiller that has had any real effect. My family (father, daughter and I) have scored some mutation that means that opioids have little to no effect and we allergic to NSAIDs (my grandfather died because he was prescribed oral Voltaren – he bled to death internally after taking his first dose). When I was in the 35th hour of giving birth, the anaesthetist asked me whether I had been a frequent user of heroin because he could not numb me up at all for an emergency C-Section and he was freaking out! Of course, I have never taken any illicit drugs, so I was confused and offended by the suggestion, but that was how I found out that morphine and several other drugs did not work on me. Having noted the above, saying “don’t prescribe Tramadol” may make sense for many people, but for me it was the first time ANY medication had ever relieved pain. Doctors tend to read suggestions such as yours and assume that it is a blanket “do not prescribe”. Perhaps an evenhanded approach which traverses the benefits of the only medication that works on some of us would be useful?

    Liked by 1 person

    1. Zyp Czyk Post author

      You are right. I should know better than to assume anything always works or always doesn’t.

      I just had an opioid training class from my doctor’s office this afternoon and they told us that although tramadol acts on the same mu receptors as opioids do, the drug itself is a laboratory creation. That explains why it can work for folks who don’t respond to opioids.

      So tramadol is definitely an option even when opioids are not. Thanks for pointing this out.


    2. Sara Harrison

      I as well as others biologically related to me also don’t find morphine and derivatives effective. With 7 orthopedic surgeries in the past 8 years and neuropathy, I have been prescribed Oxy many times. I have a bad reaction and don’t find that it is effective as Tramadol. I have no side effects from Tramadol. Never had withdrawal symptoms. Without it, I am not functional and independent in basic, daily life. I had been taking it twice per day WITH NSAIDS. No way that NSAID alone is as effective as the Tramadol for my level of pain.

      What you have reported are simply the possible untoward effects of Tramadol. Any medication, including all of the NSAIDS have the potential for rare, unexpected response in certain individuals. I was a nurse manager before my injury. We both know that every single medication available “may not work” and “may hurt our patient.” Clinical trials prior to marketing demonstrate whether a drug is clinically safe and effective most of the time. The details of potential side effects and of rare untoward responses are already listed in the PDR. Let’s not pretend that Tramadol is unique in the potential to not work and hurt our patients.

      Then, you go on to list the responses to overdose. This is simply irresponsible fear-mongering. A patient could experience far worse consequences with overdosing on insulin or anti-hypertensives than those listed here for Tramadol. Yet, you don’t suggest limiting insulin prescriptions. Many medications such as insulin, steroids, and SSRI completely change the body’s normal function. Even nasal decongestant sprays alter body chemistry and neural receptors. But, you wouldn’t prescribe them in the first place unless the body’s normal function is already atypical to the point of symptomatic.

      Underlying this is the moralization of addiction and of pain. Neither are any more moral issues than diabetes, hypertension, and high cholesterol. Most diabetes is “type II” or insulin resistant due to a lifetime of improper eating. And yet, there is no hesitation in writing prescriptions for diseases that one could just as easily refuse to treat out of moral disfavor.

      My injury is not a moral weakness. I injured my back taking care of patients. The pain isn’t a moral issue. I deserve to have medications that have passed clinical trials as safe and effective. Which in my case, there have been no bizarre side effects – but which have been proven effective over the course of several years. BTW, my liver enzymes are creeping up. You know as well as I do whether this is more likely the effect of the Tramadol or the Naprosyn. What am I going to take after my liver is damaged?


      1. Zyp Czyk Post author

        I’m sorry I was generalizing – and I already apologized in an earlier comment too.

        For *most* pain patients, tramadol is not strong enough to help, but of course there are *always* exceptions.



Other thoughts?

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.