What’s Up With Tramadol Falling Out of Favor?

Confession: I didn’t quite get as far as I wanted to in the opioid blog series this summer. Planning for our epic MMU kickoff got in the way (and it was totally worth it!). But, I’m back on the bandwagon when it comes to talking about this hot topic – in a practical manner. One topic that come up at the kickoff of our residency-like program was Tramadol. I’ve prescribed Tramadol often for patients in the past as a non-opioid(ish) pain medication option. And, it works (sometimes).

If you too are a nurse practitioner who’s trying to avoid prescribing too many opioids in the face of the abuse epidemic, and one who isn’t in favor of over-treating pain and tempting patients with addiction, Tramadol seems like a good option for pain relief. Unfortunately however, Tramadol has fallen out of favor in recent years. While it is less addictive than medications like Morphine and Oxycodone, it does have abuse potential not to mention some pretty nasty side effects and drug-drug interactions.

If you’re a Tramadol prescriber, here’s the down and dirty on what you need to be aware of with this drug.

Medication Class Confusion

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Tramadol has an identity crisis. It’s like sorbet. It’s not quite ice cream and it’s not quite an icee – it’s somewhere in the middle. As far as it’s action in the body, Tramadol has antidepressant-like activity and opioid-like activity. To get molecular, Tramadol works by binding to mu receptors (similar to opioid medications like Percocet) and acts as an SNRI (think Cymbalta and Effexor).

Overall, Tramadol is commonly prescribed as a weak opioid with pain relieving potential somewhat similar to codeine. It’s often perceived to be a better option than stronger opioids like morphine or oxycodone for patients whose pain is not as severe.

Dual-Action Doesn’t Mean It’s Twice As Good

An antidepressant/opioid combo sounds like it should be pretty awesome. When we’re in pain, a mood boost along with pain control seems like it would be a fix-all for what ails you. However in this case, as Emergency Medicine blogger Tox and Hound describes it “I like to think of Tramadol as what would happen if codeine and Prozac had a baby, and that baby grew into a sullen, unpredictable teenager who sometimes kicked puppies and set fires”.

Here’s why. When Tramadol is metabolized, some of the drug is essentially converted in the body from an SNRI to an opioid giving it that dual-action reputation. But, Tramadol is metabolized differently based on individual genetic makeup (the CYP2D6 system if we’re being technical). Some individuals are “poor metabolizers”, others are “intermediate (normal) metabolizers” and yet others are “ultrarapid metabolizers”. So, you never know if your patient is going to be getting some opioid effect, a lot of opioid effect, or hardly any opioid effect at all. You get a totally unknown ratio of SNRI and opioid circulating with an unpredictable result. Essentially, you’re taking a guess when it comes to prescribing Tramadol. And, those patients who tell you it doesn’t work for them can’t be automatically deemed drug seekers – they’re probably poor metabolizers.

Drug Interactions (Of Course!)

Tramadol is one of those meds that you don’t want to ignore when those pesky drug alert boxes pop up in the EMR as you’re prescribing. Given it’s SNRI activity, serotonin syndrome is a risk with patients taking Tramadol along with SSRIs, SNRIs and other antidepressants or medications that can precipitate serotonin toxicity. 

One More Thing to Worry About: Side Effects


Tramadol is notorious for causing seizures, especially at high doses. This is particularly true in patients taking other medications known to reduce seizure threshold. If you do choose to start a patient on Tramadol, initiating therapy at a low dose and doing a thorough med review and history is in order. 


A relatively new finding associated with Tramadol use is hypoglycemia. Hospital records in the United Kingdom show that pateints beginning Tramadol treatment were three times more likely to be hospitalized with hypoglycemia in the subsequent 30 days than those taking codeine. While the mechanism remains unclear, be aware of this risk particularly in diabetic patients. 


While providers often turn to Tramadol as a ‘sort-of’ opioid with a lower addiction potential, the medication is still ripe for abuse. Physical dependence and even Tramadol-related deaths are on the rise. So, even though Tramadol doesn’t have the reputation of say ‘oxy’ when it comes to addiction, this is a real concern. 

What’s the Verdict?

Tramadol can be effective for pain relief in some (but not all) people. The drug also comes with some pretty nasty side effects and risks. It’s up to you whether you include Tramadol in your pain relief arsenal, but if you choose to do so, prescribe with extreme caution. 


You Might Also Like: Understanding Opioid Strengths and Other Prescribing Pearls 


2 thoughts on “What’s Up With Tramadol Falling Out of Favor?”

  1. Tramadol lost favor with many physicians and NP’s when it was added to the schedule of controlled substances in 2008. The abuse potential has been exaggerated in the last few years, and serotonin syndrome is rare, even in those taking tramadol with high dose SSRIs. It’s cheap and been around for a long time, so casting it in negative light is beneficial for those wanting to push newer drugs still under patent. Unlike codeine, tramadol has appetite suppressant effects, and that may explain the increase in hypoglycemic incidence. An RCT or even retro trail would be interesting, but who would fun it? No money there.

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