Do Antidepressants Prevent Pain Relief After Surgery?

Surgery can be quite painful. Thank goodness for anesthesia! Imagine what it would be like if you had to have an appendectomy or knee replacement surgery while wide awake. Ouch! Fortunately, you can sleep right through such operations. But once the surgery is over and you do wake up, you will need strong pain medicine. Some antidepressants prevent pain relief because they interfere with the analgesic effect. Do surgeons know about this drug interaction?

How Do Antidepressants Prevent Pain Relief?

I apologize for a cheesy metaphor, but this is the best I could come up with to explain this drug interaction problem. Say you are on a long airplane flight and are watching a movie on your iPad or listening to your favorite music. You are wearing some very nice noise-canceling headphones. They eliminate most of the sound around you, including the sounds of the jet engines and those annoying announcement over the PA system.

While you are totally focused on either the music or the movie, one of the attendants gets on the PA system and announces that you are about to encounter turbulence. Your fancy headphones pretty much cancel out the message.

When you stand up to go to the bathroom, the flight attendant gives you a tongue lashing for having missed his stern message to stay seated. The noise-canceling headphones pretty much blocked your ability to hear outside messages, including the one to stay seated!

The antidepressant medicines surgical patients may be taking long before an operation may sabotage the effectiveness of some powerful pain meds. It’s as if the opioid analgesic that is prescribed after surgery is trying to speak clearly, telling your brain to ignore the pain.

If, however, the antidepressant you have been taking is muffling the pain-easing message, your brain won’t hear the call for relief from the opioid analgesic. If surgeons don’t know that some antidepressants prevent pain relief, they may prescribe the wrong analgesic. Ouch!

Why You Should Care that Some Antidepressants Prevent Pain Relief:

We recently heard from a reader who experienced significant pain after knee replacement surgery. It was a wake up call for everyone.

Knee Replacement Surgery Hurt Like Hell!

Q. I recently had to have additional surgery after a total knee replacement. Nothing the hospital gave me for pain helped at all.

My neighbor told me that after her surgery, she had the same experience. Her doctor told her that certain individuals on antidepressants have an issue with opioids not helping with pain. The research was done at Stanford in 2019.

I’m only taking Tylenol, and I am still in a lot of pain. Why don’t surgeons know that antidepressants make opioids ineffective?

A. We are so sorry to learn you are in pain after follow-up knee surgery. We are, however, grateful that you told us about this research (PLoS One, Feb. 6, 2019). More surgeons should be aware of this interaction.

Although opioid-type medications have come under a lot of scrutiny in recent years, they are still the first-line treatment for postoperative pain. At last count, 44 million Americans take antidepressant medications such as bupropion, duloxetine, fluoxetine, and paroxetine.

These antidepressants block the action of an enzyme called CYP2D6. This natural compound is essential for activating pain relievers such as hydrocodone, codeine and tramadol (Expert Opinion in Drug Safety, Feb 23, 2023). That explains why people taking such antidepressants might not get adequate pain relief from opioid-type analgesics. In addition, they seem more susceptible to post-op delirium and may need longer hospitalization.

Researchers Describe Why Some Antidepressants Prevent Pain Relief:

Please do not take our word on this interaction.

Here is what these University of California, San Francisco investigators have to say about why certain antidepressants prevent pain relief:

“Adverse events due to drug-drug interactions may be of clinical significance and are preventable.

“Furthermore, achieving a balance between patient safety and optimal pain management requires a better understanding of drug-drug interactions in surgical patients. A study assessing the difference between preoperative and postoperative pain found that surgical patients taking inhibiting antidepressants and hydrocodone, codeine, or tramadol had significantly worse postoperative pain control compared to patients taking non-inhibiting antidepressants.”

Conclusions:

“Careful consideration to drug-drug interactions and risk of related adverse events remains critical in the safe and optimal management of postoperative pain in patients taking concomitantly antidepressants.”

Patients and Families Must Discuss Pain Management Before Surgery!

Here is our take-home message from this research. If a patient is taking an antidepressant prior to major surgery she must not stop the medicine! Doing so could trigger horrific withdrawal symptoms. You can learn more about this problem at this link.

“Antidepressant Withdrawal Feels Like Circles of Hell“

The antidepressants that have been reported to interfere with pain control include bupropion, duloxetine, fluoxetine and paroxetine. If your surgeon is not familiar with this interaction and you are taking one of those antidepressants, make sure she sees this article and the research supporting it.

If the patient undergoing surgery is taking one of those antidepressants, pain control could be more challenging. This is especially true if the surgeon is used to prescribing tramadol or hydrocodone to manage pain. Codeine may also pose problems, since it too must be converted to an active metabolite to be effective at easing pain.

There is some confusion about oxycodone. The authors provide these contradictory sentences:

“Adverse events due to drug-drug interactions may be of clinical significance and are preventable. A literature review suggested that moderate-to-strong inhibiting antidepressants should be avoided in patients taking codeine. Another study found an increased risk of opioid overdose-related hospitalizations and emergency department visits in older adults taking inhibiting antidepressants fluoxetine or paroxetine who were initiated on oxycodone. Conversely, others have recommended to prescribe direct acting opioids such as oxycodone in patients taking inhibiting antidepressants. Hence, further research is needed to elucidate the risk of adverse events in patients taking antidepressants and opioid analgesics concomitantly.”

The article published in PLOS One (Feb. 6, 2019) mentions these “non-prodrug opioids”:

• Morphine
• Fentanyl
• Hydromorphone
• Oxycodone
• Methadone

That suggests that they might be less vulnerable to the antidepressant effect. Surgeons may need to consider one of those powerful analgesics for better pain relief if a patient is taking an antidepressant that could interfere with CYP2D6.

Confused? We do not blame you. That is why it is imperative that your surgeon do her due diligence prior to prescribing pain meds to prevent post-surgical pain.

The authors of the article in Expert Opinion in Drug Safety, Feb 23, 2023 state this crucial point:

“This study provides evidence of the patient safety implications of drug-drug interactions between antidepressants and opioid analgesics. This work highlights the importance of routine monitoring of patients undergoing surgery who may be at risk of post-operative complications.”

Final Words:

You never know when you might need surgery. Appendicitis can show up out of the blue and require emergency surgery. A fall could lead to unexpected hip surgery. We could go on and on, but you get the picture. You really need to be prepared for any contingency.

Chances are that after reading this article you will mostly forget what you have read…except for the idea that some antidepressants could reduce the effectiveness of certain powerful pain meds. That means you could suffer after surgery if you are 1) taking one of the listed antidepressants and 2) prescribed a prodrug opioid analgesic after surgery.

That is why you might want to keep this article in a place where you could find it, just in case you are taking a relevant antidepressant and need unexpected surgery. You would want to give it to the surgeon before they put you to sleep!

Perhaps you know someone who might need surgery some day. Why not send them to this article or post it on social media by scrolling to the top of the page and clicking on one of the icons? Where else can you get this kind of information? We would be grateful if you encourage friends and family to subscribe to our free newsletter at this link. That way, they too could read about drug interactions that could have a profound impact on their well being.